Article

Living Cellular Construct for Increasing the Width of Keratinized Gingiva: Results From a Randomized, Within-Patient, Controlled Trial

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The standard of care for increasing keratinized gingiva adjacent to teeth that do not require root coverage is the free gingival graft (FGG). A pilot study indicated that the use of a living cellular construct (LCC) could be effective in this clinical scenario. A pivotal, multicenter, randomized, within-patient, controlled, open-label trial was conducted (N = 96 patients). After removing the mucosa and keratinized gingiva from the test site, either an LCC or FGG was applied. The primary efficacy endpoint was the ability of the LCC to regenerate ≥2 mm keratinized gingiva at 6 months. Secondary measures were the same color and texture as the adjacent tissue, a 1-mm width of keratinized gingiva at 6 months, patient treatment preference, surgical site sensitivity at 1 week, and patient-reported pain after 3 days. Safety was assessed by reports of adverse events. At 6 months, the LCC regenerated ≥2 mm of keratinized gingiva in 95.3% of patients (81 of 85 patients; P <0.001 versus a 50% predefined standard). As expected, the FGG generated more keratinized gingiva than the LCC (4.57 ± 1.0 mm versus 3.2 ± 1.1 mm, respectively). The gingiva regenerated with the LCC matched the color and texture of the adjacent gingiva. All patients achieved ≥1 mm keratinized gingiva with the LCC treatment by 6 months, and more patients preferred treatment with the LCC than with the FGG. No difference in sensitivity or pain was noted between the treatments. The treatments were well tolerated, and reported adverse events were typical for this type of periodontal surgery. The use of an LCC may provide a safe and effective therapy for augmenting the zone of keratinized gingiva.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... 22, 25, 3 0-35 Several studies have shown that patient preference was seldom in line with the clinical-and professional-outcome, and more often towards the less invasive procedure. [36][37][38][39][40] Tissue engineering strategies also have the potential of promoting an accelerated healing and recovery, together with periodontal regeneration, owing to the beneficial effect of these living cells and growth factors/biologic agents. [41][42][43][44][45] ...
... 10,24 Fibroblasts and keratinocytes are the somatic cells that have been employed for oral soft-tissue reconstruction . 24,38,50,[59][60][61] These cells are usually obtained from neonatal foreskin or from the actual patients with a punch biopsy. Autogenous cultured and expanded fibroblasts have also been used for root coverage procedures, widening of attached gingiva, and papilla augmentation. ...
... A full-text assessment was performed for 283 articles. Based on our predetermined inclusion criteria, 128 randomized controlled trials utilizing tissue engineering strategies were included in the qualitative assessment 36,38,71,72,79,82,87,101,135,[31][32][33][59][60][61][63][64][65][67][68][69] ( Tables 1-14). Among them, 59 trials evaluated the efficacy of tissue F I G U R E 7 Human and porcine-derived acellular dermal matrices before and after rehydration. ...
Article
Full-text available
Scientific advancements in biomaterials, cellular therapies, and growth factors have brought new therapeutic options for periodontal and peri‐implant reconstructive procedures. These tissue engineering strategies involve the enrichment of scaffolds with living cells or signaling molecules and aim at mimicking the cascades of wound healing events and the clinical outcomes of conventional autogenous grafts, without the need for donor tissue. Several tissue engineering strategies have been explored over the years for a variety of clinical scenarios, including periodontal regeneration, treatment of gingival recessions/mucogingival conditions, alveolar ridge preservation, bone augmentation procedures, sinus floor elevation, and peri‐implant bone regeneration therapies. The goal of this article was to review the tissue engineering strategies that have been performed for periodontal and peri‐implant reconstruction and implant site development, and to evaluate their safety, invasiveness, efficacy, and patient‐reported outcomes. A detailed systematic search was conducted to identify eligible randomized controlled trials reporting the outcomes of tissue engineering strategies utilized for the aforementioned indications. A total of 128 trials were ultimately included in this review for a detailed qualitative analysis. Commonly performed tissue engineering strategies involved scaffolds enriched with mesenchymal or somatic cells (cell‐based tissue engineering strategies), or more often scaffolds loaded with signaling molecules/growth factors (signaling molecule‐based tissue engineering strategies). These approaches were found to be safe when utilized for periodontal and peri‐implant reconstruction therapies and implant site development. Tissue engineering strategies demonstrated either similar or superior clinical outcomes than conventional approaches for the treatment of infrabony and furcation defects, alveolar ridge preservation, and sinus floor augmentation. Tissue engineering strategies can promote higher root coverage, keratinized tissue width, and gingival thickness gain than scaffolds alone can, and they can often obtain similar mean root coverage compared with autogenous grafts. There is some evidence suggesting that tissue engineering strategies can have a positive effect on patient morbidity, their preference, esthetics, and quality of life when utilized for the treatment of mucogingival deformities. Similarly, tissue engineering strategies can reduce the invasiveness and complications of autogenous graft‐based staged bone augmentation. More studies incorporating patient‐reported outcomes are needed to understand the cost‐benefits of tissue engineering strategies compared with traditional treatments.
... 91 The lower morbidity, unlimited blood supply, and regeneration of a site-appropriate tissue compared with the autogenous gingiva have been considered as the main advantages of graft alternatives. 92,93 In particular, the cultivation of human living keratinocytes and fibroblasts into scaffold matrices have also been investigated for creating an autogenous soft tissue graft equivalent, showing promising outcomes however inferior to FGG. 92,94,95 Our results demonstrated the efficacy of LCC in KT augmentation compared with untreated sites and APF. It is important to highlight that KT baseline significantly affected the KT gain for LCC treatment. ...
... According to McGuire et al., and as also suggested by Lang and Löe, 16 achieving a minimum of 2 mm keratinized gingiva is generally accepted as an end point of soft tissue augmentation. 94 LCC was found capable of regenerating ≥2 mm KT in 95.3% of patients, 94 which can lead to a debate of whether it is better to obtain greater KT (with the gold standard FGG) or to regenerate a smaller, however arguably sufficient amount of KT in favor of patient-related and esthetic outcomes. ...
... According to McGuire et al., and as also suggested by Lang and Löe, 16 achieving a minimum of 2 mm keratinized gingiva is generally accepted as an end point of soft tissue augmentation. 94 LCC was found capable of regenerating ≥2 mm KT in 95.3% of patients, 94 which can lead to a debate of whether it is better to obtain greater KT (with the gold standard FGG) or to regenerate a smaller, however arguably sufficient amount of KT in favor of patient-related and esthetic outcomes. ...
Article
Background: The periodontal phenotype consists of the bone morphotype, the keratinized tissue (KT) and gingival thickness (GT). The latter two components, overlying the bone, constitute the gingival phenotype (GP). Several techniques have been proposed for enhancing or augmenting KT or GT. However, how phenotype modification therapy (PMT) affects periodontal health and whether the obtained outcomes are maintained over time have not been elucidated. Aim: The aim of the present review was to summarize the available evidence in regard to the utilized approaches for gingival PMT and assess their comparative efficacy in augmenting KT, GT and in improving periodontal health using autogenous, allogeneic and xenogenic grafting approaches. Materials and methods: A detailed systematic search was performed to identify eligible randomized clinical trials (RCTs) reporting on the changes in GT and KT (primary outcomes). The selected articles were segregated into the type of approach based on having performed a root coverage, or non-root coverage procedure. A network meta-analysis was conducted for each approach to assess and compare the outcomes among different treatment arms for the primary outcomes. Results: A total of 105 eligible RCTs were included. 95 pertaining to root coverage (3,539 treated gingival recessions), and 10 for non-root coverage procedures (699 total treated sites). The analysis on root coverage procedures showed that all investigated techniques (the acellular dermal matrix (ADM), collagen matrix (CM), connective tissue graft (CTG)) are able to significantly increase the GT, compared to treatment with flap alone. However, KT was only significantly increased with the use of CTG or ADM. Early post-treatment GT was found to inversely predict future gingival recession. For non-root coverage procedures, only the changes in KT could be analyzed; all investigated treatment groups (ADM, CM, free gingival graft (FGG), living cellular constructs (LCC), in combination with an apically positioned flap (APF)), resulted in significantly more KT than treatment with APF alone. Additionally, the augmented GT was shown to be sustained, and KT displayed an incremental increase overtime. Conclusions: Within its limitations, it was observed that any graft material was able to significantly enhance GT, while KT in root coverage procedures was significantly enhanced with CTG and ADM, and in non-root coverage procedures, with ADM, CM, FGG and LCC compared to APF alone. The autogenous soft tissue graft (CTG/FGG) proved to be superior in all comparisons for both outcomes of GT and KT. This article is protected by copyright. All rights reserved.
... At the same time, cell sheets prevent unforeseen effects of the matrix as well as the action of proteolytic enzymes on surface molecules, hence representing a more innovative approach [4,7,11,15]. It has been understood that living cells, when used for the above-mentioned purpose, interact well with the host tissues modulating cytokine and growth factor expression and release, which heralds the process of wound healing and regeneration [16,17]. It is also understood that living cell constructs can be fabricated from stem cells under the influence and inducement of various chemical signals that can be administered in vitro. ...
... When they are placed in the surgical site, they aid orchestrated healing by timed production and release of growth factors and cytokines, such as vascular endothelial growth factor. This stimulates angiogenesis and fosters the cells in the wound microenvironment to differentiate into an array of different cell types in a timed manner for complete regeneration [16]. The present study is novel; a live cell construct composed of DPSC has been successfully initiated and carried out under the influence of quercetin. ...
Article
Full-text available
Autogenous gingival grafts used for root coverage or gingival augmentation procedures often result in donor site morbidity. Living cellular constructs as an exogenous alternative have been proven to be associated with lower morbidity. With the available background information, the present study aims to assess if quercetin‐induced living cell constructs, derived from dental pulp stem cells, have the potential to be applied as a tool for soft tissue augmentation. The characterized dental pulp stem cells (positive for CD73, CD90, and negative for CD34, HLA‐DR) were expanded in Dulbecco’s Modified Eagle’s medium (DMEM) supplemented with 10 mM quercetin. The handling properties of the quercetin‐induced dental pulp stem cell constructs were assessed by visual, and tactile sensation. A microscopic characterization using hematoxylin and eosin staining, and qRT‐PCR‐based analysis for stemness‐associated genes (OCT4, NANOG, SOX2, and cMyc) was also performed. Dental pulp stem cells without quercetin administration were used as the control. Dental pulp stem cell constructs induced by quercetin easily detached from the surface of the plate, whereas there was no formation in the control cells. It was also simple to transfer the induced cellular construct on the flattened surface. Microscopic characterization of the constructs showed cells embedded in a tissue matrix. Quercetin also increased the expression of stemness‐related genes. The use of quercetin‐induced DPSC living constructs for soft tissue augmentation could provide an alternative to autogenous soft tissue grafts to lower patient morbidity and improve esthetic outcomes.
... 9 Furthermore, studies evaluating esthetics have suggested that the color blend and texture match may be superior when KT augmentation is performed using an alternative graft. 15 The novelty of this manuscript is that it is able to shed light on the clinical scenario in which a patient chooses an alternative to autogenous tissue harvesting for the correction of mucogingival defects. This systematic review and meta-analysis aimed to compare clinical outcomes and width of KT around teeth, following the soft tissue alternatives and FGG procedures. ...
... Adequate sequence generation was reported in 5 of 7 studies, 17,18,23 and adequate allocation concealment was reported only in 3 studies. 12,15,18 None of the studies reported blinding of participants and personnel. In addition, outcome assessors were blind only in 2 studies. ...
Article
Objectives This systematic review and meta-analysis aimed to compare clinical outcomes and width of keratinized tissue (KT) around teeth, following the soft tissue alter- natives and free gingival graft (FGG) procedures. The specific graft materials that were explored were extracellular matrix membrane, bilayer collagen membrane, living cellular construct, and acellular dermal matrix. Methods Four different databases were queried to identify human controlled clinical trials and randomized controlled clinical trials that fulfilled the eligibility criteria. Relevant studies were identified by 3 independent reviewers, compiling the results of the electronic and handsearches. Studies identified through electronic and handsearches were reviewed by title, abstract, and full text using Covidence Software. Primary outcome in the present study was change in the width of KT. Results of the included studies were pooled to estimate the effect size, expressed as weighted mean differences and 95% confidence interval. A random-effects model was used to perform the meta-analyses. Results Six hundred thirty-eight articles were screened by title, 55 articles were screened by abstracts, and 34 full-text articles were reviewed. Data on quantitative changes in width of KT were provided in 7 studies. Quantitative analyses revealed a significant difference in changes in width of KT between patients treated with soft tissue alternatives and patients treated with FGGs (P < .001). The weighted mean difference of changes in the width of KT was 21.39 (95% confidence interval: 21.82 to 20.96; heterogeneity I 5 70.89%), indicating patients who were treated with soft tissue alternatives gained 1.39 mm less KT width compared with the patients who received free gingival graft. Conclusions Based on the clinical outcomes, the results of this systematic review and meta-analysis showed that soft tissue alternatives result in an increased width of KT. Patients in the soft tissue alternatives group obtained 1.39 mm less KT compared with those in the FGGs group.
... The implantation of living cells in scaffold materials (tissue engineered constructs, TECs) has represented a new line in the field of soft tissue grafting. It has been suggested that one of the main advantages of living cell-based technology is the ability to communicate with the host by modulating cytokine expression 1,2 . Bioengineered living cellular therapy can be classified based on the cell types contained in the carrier matrices. ...
... due to the fact that the material acts not as a graft but more as a cell-delivery therapy encouraging the adjacent native cells to migrate into and over it 1,2 LCC group compared to FGG at the early stage of wound healing 35 . Furthermore, most patients preferred the LCC treatment than FGG 1 with no adverse events reported. ...
Article
The cultivation of human living cells into scaffolding matrices has progressively gained popularity in the field of periodontal wound healing and regeneration. Living constructs based on fibroblasts, keratinocytes alone or in combination have been developed and used as alternatives to autogenous soft tissue grafts in keratinized tissue (KT) augmentation and in root coverage procedures. Their promising advantages include reduced patient morbidity, unlimited graft availability, and comparable esthetics. This manuscript reviews soft tissue augmentation and root coverage procedures using bioengineered living cellular therapy and highlights their expected clinical, esthetic and patient‐related outcomes. This article is protected by copyright. All rights reserved
... In contrast, Morelli [62], Nevins [63], and McGuire et al. [64,65] used a living cellular construct (LCC) for periodontal soft tissue reconstruction. LCC consists of type I bovine collagen populated with allogeneic human foreskin fibroblasts overlaid by allogeneic human foreskin keratinocytes. ...
... LCC consists of type I bovine collagen populated with allogeneic human foreskin fibroblasts overlaid by allogeneic human foreskin keratinocytes. The LCC was consequently proved to be a safe and effective therapy for augmenting the zone of keratinized gingiva by their randomized controlled trial [65]. This study became a breakthrough in oral mucosa TE. ...
Chapter
Oral mucosa primarily acts as a barrier against the external harmful environments. Loss of its barrier function due to diseases or injury will cause significant dysfunction within the oral cavity. Surgeons are frequently confronted with finding an acceptable source of autologous grafts for reconstruction of oral mucosa defects. Thus, there is a need to overcome these shortcomings of limited supply and donor site morbidity in the current surgical management/reconstruction of oral mucosa defects. Tissue engineering/regenerative medicine is an interdisciplinary field of developmental biology, life sciences, and engineering efforts that attempts to address challenges in the clinical arena. The understanding of the growth and functions of cells, the principles and methods of engineering, and the signals regulating cellular responses drives the fabrication of matrices and the design of tissue assembly to generate tissue-engineered products for in vivo and in vitro applications. Progress has been made over the years in the development of tissue-engineered substitutes that mimic human oral mucosa, either to be used as grafts for the replacement of mucosa defects, or for the in vitro oral mucosa models while tissue engineering of oral mucosa is still in its infancy. An increased understanding of stem cells, scaffolding, and signaling with extracellular matrix interactions will make its future possible. This chapter gives a comprehensive overview of the developments and future prospects of tissue-engineered constructs as oral mucosa substitutes for tissue repair and regeneration.
... 1,2 Nowadays, autogenous soft tissue grafts are routinely used not only for increasing keratinized tissue and achieving for root coverage [3][4][5] , but also in the context of alveolar ridge preservation 6,7 , guided bone regeneration 8 , and peri-implant soft tissue reconstruction. [9][10][11] Although alternative materials have been introduced in an attempt to reduce patient morbidity 4,[12][13][14][15] , autogenous soft tissue grafts are still considered the gold standard treatment for periodontal and peri-implant plastic surgeries. [16][17][18][19][20] Several palatal harvesting approaches have been described throughout the literature. ...
... Patient morbidity, satisfaction and willingness for retreatment have been evaluated as endpoints in clinical trials aiming at comparing two or more treatments. 4,13,42,45,46 The present study also suggested that both methods of harvesting (FGG and the single incision technique for obtaining a subepithelial CTG) have similar patient morbidity, as previously demonstrated by Zucchelli et al. 23 Additionally, we found that surgical sites including ≥ 3 teeth were more likely to have higher pain responses and lower willingness to retreat. This may be due to the bigger graft width (in terms of mesio-distal dimensions), which is contradictory with previous studies have failed to demonstrate a correlation between perceived pain and graft width. ...
Article
Background: Patient-reported outcomes have received a great deal of interest in periodontal plastic procedures. However, their evaluation has mainly been short-term. Thus, the aim of this study was to evaluate the impact of soft tissue grafting procedures conducted over a decade ago on the willingness of a patients to undergo the surgery again. Methods: Subjects that received an autogenous soft tissue graft over 10 years ago were screened and invited for a survey. Their response was only analyzed if they were able to correctly identify the sites of the surgical procedures. Dichotomous questions and visual analogue scales (VASs) were used to assess self-reported pain, willingness to retreat and satisfaction. Results: Fifty-two patients were included in the analyses. Higher pain was reported for mandibular sites, and treated areas including ≥ 3 teeth (p<0.01). Willingness to retreatment was 84.6% and it was negatively associated with self-reported pain measures, the arch location (mandible), and number of treated sites (≥3 teeth) (p<0.01). Mean satisfaction rate was 86.9 ± 13.65 (VAS) and showed a positive correlation with willingness to retreat (p<0.01). Having a complete root coverage at the recall visit was also significantly associated with higher patient satisfaction scores (p<0.01). Conclusions: Patient experience of previous autogenous soft tissue grafting has an influence on their decision to undergo future treatment. Willingness to retreat was negatively affected by mandibular sites, larger treated areas and the perceived pain, while presenting with complete root coverage was significantly associated with patient satisfaction. This article is protected by copyright. All rights reserved.
... The MCAT procedure yielded ≥ 2 mm KT in 100% and ≥ 3 mm KT in 80% of the patients. Thus, both FGG and MCAT could be considered as satisfactory for increasing KT as an endpoint of gingival augmentation [36,37]. However, if increasing KT more than 2 mm is the main goal, then FGG still seems to be the advisable procedure in the lower anterior region. ...
Article
Full-text available
Objectives The gingival thickness (GT) and keratinized tissue (KT) height are defined as the gingival phenotype. Both the modified coronally advanced tunnel technique (MCAT) and free gingival grafts (FGG) are used in modifying the gingival phenotype. This study aims to compare MCAT and FGG in gingival phenotype modification. Materials and methods One hundred and forty recessions in 50 patients with thin and insufficient keratinized tissue at the anterior mandible were treated with either MCAT or FGG. GT, KT height, recession depth, recession width, probing depth, and clinical attachment level were evaluated at baseline and 6 weeks, 6 months, and 12 months. GT change, KT change, root coverage (RC), clinical attachment gain, and complete root coverage (CRC) were calculated. The wound healing index, tissue appearance, patient expectations, aesthetic, and dentin hypersensitivity were assessed at baseline and 6 months. Results All periodontal variables showed significant change from baseline to 12 months in both groups (p < 0.05). While FGG resulted in more KT change (p < 0.001), all MCAT sites showed at least 2 mm KT change in 12 months. MCAT resulted in greater GT change (p < 0.05) and RC (p < 0.003). In contrast, there was no significant inter-group CRC difference (p = 0.523). All patient-based variables were favorable to MCAT (p < 0.05), except dentin hypersensitivity (p = 0.225). Conclusions Both techniques were successful in terms of gingival phenotype modification in the anterior mandible. Additional GT increase, RC, and patient-based outcomes favored MCAT, though KT change proved greater with FGG. Clinical relevance Clinicians may choose MCAT for higher GT increase whereas FGG for more KTC. Trial registration number: NCT04690140 and date: 12/26/2020.
... 33,39 SDG ile karşılaştırıldığı çalışmalarda, SDG ye göre daha az keratinize doku kazancı sağlamış olsa da, renk ve yapı bakımından çevre dokular ile uyumu çok daha üstün bulunmuştur. 40 ...
Article
Full-text available
mplant uygulamalarındaki bilimsel gelişmeler sayesinde, tıbbi başarı oranı gün geçtikçe artmakta ve hasta beklentileri daha iyi karşılanabilmektedir. İmplant rehabilitasyonu artık sadece çiğneme ve fonetik işlevlerin geri kazandırılma-sında bir araç değildir. Aynı zamanda, dişsiz bölgelerin yapısal ve estetik rejeneras-yonu ile ilgili ideal tedavi sonuçlarına ulaşılması, modern implant dişhekimliğinin en önemli hedeflerinden biri haline gelmiştir. 1,2 Dental implantlarda "uzun süreli fonksiyonel ve estetik başarı", sert ve yumu-şak dokuların denge içinde olmasına bağlıdır. Böylelikle, bakteri plağı ve stresin eli-Turkiye Klinikleri J Periodontol-Special Topics 2017;3(2):85-93 85 Mukogingival Cerrahinin Peri-İmplant Doku Sağlığındaki Rolü Ö ÖZ ZE ET T Dental implantlarda fonksiyon ve estetiğin uzun süreli başarısı, sert ve yumuşak dokuların denge içinde olmasına bağlıdır. Bununla birlikte, implant öncesi mukogingival ilişkilerin göz ardı edilmesi, implantasyon sırasında veya sonrasında sert ve yumuşak dokuları ilgilendiren önemli komplikasyonlara yol açabilir. Mukogingival cerrahi teknikler yapışık dişeti ve keratinize dişetini içeren çeşitli yumuşak doku defektlerinin düzeltilmesinde uygulanan rutin tedavi yöntemleri ola-rak kabul görmektedir. Güncelliğini sürekli koruyan bu tekniklerin implantolojiye adapte edilmesi ile " peri-implant plastik cerrahi" kavramı ortaya atılmıştır. Peri-implant plastik cerrahi yaklaşım-lar; sert ve yumuşak dokuların her ikisini de kapsayan tatmin edici estetik sonuçlar sunarken, ok-luzal kuvvetlere ve mukogingival strese karşı direnç gösteren sağlıklı peri-implant dokuların oluşumuna katkı sağlayabilen yöntemlerdir. İmplant sonrası oluşabilecek peri-implant mukositis ve peri-implantitisi içeren sert ve yumuşak doku problemlerinin tedavisi peri-implant plastik cer-rahi uygulamaların bir diğer önemli amacıdır. A An na ah ht ta ar r K Ke el li im me el le er r: : Mukogingival cerrahi; peri-implantitis; diş implantasyonu A AB BS ST TR RA AC CT T The long-term functional and aesthetic success of dental implants depends on a balance between hard structures and soft tissues. Neglecting pre-implant muco-gingival relationships can lead to serious complications in both of these tissue types, during or after implantation. Mucogin-gival surgery techniques have become established as routine treatments for correcting various soft tissue defects including the attached gingiva and keratinized gingiva. The concept of "peri-implant plastic surgery" has been proposed as a result of the adaptation of these current techniques to im-plantology. Peri-implant plastic surgery approaches are methods that can contribute to the development of healthy peri-implant structures able to withstand occlusal forces and mucogingival stress, while providing satisfactory aesthetic results in both soft and hard tissues. The treatment of hard structure and soft tissue problems including peri-implant mucositis and peri-implantitis that can arise post-implantation is another important goal of peri-implant plastic surgery practice. K Ke ey yw wo or rd ds s: : Mucogingival surgery; peri-implantitis; dental implantation
... Briefly, the intended purpose of tissue engineering is to provide an unlimited source of cells, growth factors and signaling molecules, as a means of substituting, restoring and regenerating the lost tissues. The relevant tissue-engineering concept involves the application of bioactive molecules and living-cell-based therapy in soft-and hard-tissue regeneration (9). ...
Article
Background and objective: Gingival recession is defined as soft and hard tissue displacement resulting in root surface exposure. The optimal outcome of gingival recession treatment is complete, predictable and long-lasting root coverage with a significant level of tissue regeneration. Tissue engineering, which applies active regeneration principles, presents the contemporary treatment approach in the restitution and regeneration of lost tissues. The objective of the present study was to evaluate and compare the clinical results of application of an autologous fibroblast cell culture (AFCC) on a collagen matrix and a connective tissue graft (CTG) placed under a coronally advanced flap (CAF), in the treatment of single and multiple gingival recessions. Material and methods: Eighteen patients from the Department of Periodontology, School of Dentistry, University of Belgrade, were randomly enrolled in this study. Inclusion criteria were the bilateral presence of Miller Class I or II single or multiple maxillary gingival recessions. A split-mouth design was used in the study. The experimental group was treated with AFCC on a collagen scaffold, which was placed under a CAF. The control group received a combination of CTG and CAF. Clinical parameters such as gingival recession coverage, keratinized tissue width, clinical attachment level and gingival index were recorded at baseline and at 12 mo postoperatively. The oral hygiene level was assessed by plaque index evaluation. Postoperative healing was evaluated through the healing index, recorded 1, 2 and 3 wk postoperatively. The final esthetic outcome was assessed using the mean root coverage esthetic score (RES). Results: Statistically significant improvement of all parameters assessed was found compared with baseline. A statistically significant difference between groups was observed only in keratinized tissue width. Greater keratinized tissue width is still obtained with the use of CTG. Regarding the tissue-healing results, no statistically significant difference was achieved. The RES results were similar for both groups. Conclusions: Within the limitations of the present study, both procedures proved to be efficient in gingival recession treatment. AFCC, as a novel tissue-engineering concept and living cell-based therapy, proved to be a reliable and successful treatment concept.
... These grafts have an advantage over skin grafts in the sense that presence of hair follicles by their growth later in the graft made this procedure less in demand; in addition autogenous gingival grafts carries the genetic nature of the keratinized mucosa. Further technological advancements came in the form of autologous cultured sheets of mucosa but these procedures caused more shrinkage of augmented tissue.[789] Hence, it sounds logical enough to compare the two procedures namely, Periosteal Fenestration and Free Mucosal Graft for increasing the vestibular depth since there is scarcity of studies comparing these two procedures. ...
Article
Full-text available
Purpose: The aim of the present study was to compare the periosteal fenestration (PF) and free mucosal graft (FMG) techniques in mandibular anterior region to increase the vestibular depth. Methodology: A total of 20 systemically healthy cases (10 patients in each group) with shallow vestibular depth and reduced width of attached gingiva in lower anterior region were included in the present study. Clinical parameters recorded included Gingival index (GI), Plaque index (PI), Oral hygiene index simplified (OHI S), Vestibular depth (VD), width of attached gingiva and post operative discomfort. Findings: The results at the end of 3 months showed that the mean GI, PI, OHI S decreased significantly and remained low throughout the study period. The mean gain in percentage of vestibular depth at the end of 3 months for group 1(PF) was 48.4% with relapse of 7.2% from the baseline. For group 2 (FMG), the mean gain in percentage of vestibular depth at the end of 3 months for was 50% with relapse of 6.2% from the baseline. The mean gain in percentage of attached gingiva at 3 months for group 1 and 2 was 65.9% and 74%, respectively. In comparison of group 1 and 2, group 2 showed better results in terms of increasing the vestibular depth and attached gingiva than group 1 although the intergroup comparison was not statistically significant. Conclusion: When aim of the clinician is to treat a patient with shallow vestibule together with reduced width of attached gingiva, the use of periosteal fenestration yields similar results to that of FMG.
... Plusieurs essais cliniques ont associé des fibroblastes gingivaux autologues à des matrices afin d'améliorer le remodelage de la membrane. Les protocoles s'appuyaient sur des matrices collagéniques ensemencées de fibroblastes et une fenestration périostée, des greffes gingivales libres avec thérapie cellulaire, des ADMA ensemencées de fibroblastes associées à des greffes de tissu conjonctif (GTC) enfoui sur des récessions, ainsi que des membranes de collagène ensemencées de fibroblastes sous un lambeau déplacé coronairement [5][6][7][8][9]. Ces études comparant les produits d'ingénierie tissulaire (IT) avec les techniques classiques ont montré des résultats satisfaisants en termes d'inflammation postopératoire, de régénération, de couleur et de texture. ...
... Mc Guire y col. (66) realizaron un estudio en 96 pacientes, los cuales recibieron en el mismo día tratamiento con IGL y en el lado contralateral Matriz Celular Viva (MCV-también denominado TCB). Se realizaron controles a la semana, 4 semanas, 3 meses y 6 meses. ...
Article
Full-text available
Objective: To describe, classify and discuss the clinical applications of biologically based biomaterials, bioactive molecules and tissue engineering being utilized in gingival recession therapy and gingival augmentation procedures in plastic periodontal surgery. In this literature review, a combination of specific search key words were used, including materials being reviewed, indicated for gingival augmentation and root coverage procedures. Materials and Methods: The following sources were consulted: Medline, Cochrane Library and manual search of specific scientific journals such as Journal of Periodontology, International Journal of Periodontics and Restorative Dentistry and Journal of Clinical Periodontology between the years 1985 and 2011. A total of 117 articles were reviewed with 74 being selected unanimously by the authors for discussion in the manuscript. These articles included controlled clinical studies, randomized clinical studies, case reports and animal studies. The selected articles were reviewed by the authors and accepted by consensus. Conclusions: 1) There is a cohort of materials that exhibit great potential which could be a viable alternative to autografts but are in need of further long term studies. 2) There is a need of research of these materials in relation to stability, safety and efficacy.
... 84 Search of site-appropriate tissue in the oral cavity has included application of living cellular sheet (LCS) in oral soft tissue therapy as a free gingival graft. 85,86 LCS is an allogenic graft composed of cultured keratinocytes and fibroblasts in bovine collagen and has been used for more than 14 years to treat patients with cutaneous wounds. [87][88][89][90] (Fig. 15). ...
Article
Full-text available
The presence of healthy attached tissue at the tooth and implant soft tissue interface correlates with long-term success and stability in function and esthetics. There are several soft tissue grafting procedures that increase the volume of keratinized tissue and provide coverage on both teeth and implants. Many of these techniques can be used in conjunction with implant placement, or after placement as a means of salvage. This article describes the techniques for augmentation of keratinized tissue as well as root and implant coverage. These tools should be in the armamentarium of oral and maxillofacial surgeons providing implant services. Copyright © 2015 Elsevier Inc. All rights reserved.
... In addition, histologic findings showed that LCCtreated sites resembled gingiva rather than alveolar mucosa. [31][32][33][34] This product is not currently available commercially. ...
Article
Background: Historically, periodontal regeneration has focused predominantly on bone substitutes and/or barrier membrane application to provide for defect fill and/or selected cell repopulation of the lesion. More recently, a number of technologies have evolved that can be viewed as emerging therapeutic approaches for periodontal regeneration, and these technologies were considered in the review paper and by the consensus group. The goal of this consensus report on emerging regenerative approaches for periodontal hard and soft tissue reconstruction was to develop a consensus document based on the accompanying review paper and on additional materials submitted before and at the consensus group session. Methods: The review paper was sent to all the consensus group participants in advance of the consensus conference. In addition and also before the conference, individual consensus group members submitted additional material for consideration by the group. At the conference, each consensus group participant introduced themselves and provided disclosure of any potential conflicts of interest. The review paper was briefly presented by two of the authors and discussed by the consensus group. A discussion of each of the following topics then occurred based on the content of the review: a general summary of the topic, implications for patient-reported outcomes, and suggested research priorities for the future. As each topic was discussed based on the review article, supplemental information was then added that the consensus group agreed on. Last, an updated reference list was created. Results: The application of protein and peptide therapy, cell-based therapy, genetic therapy, application of scaffolds, bone anabolics, and lasers were found to be emerging technologies for periodontal regeneration. Other approaches included the following: 1) therapies directed at the resolution of inflammation; 2) therapies that took into account the influence of the microbiome; 3) therapies involving the local regulation of phosphate and pyrophosphate metabolism; and 4) approaches directed at harnessing current therapies used for other purposes. The results indicate that, with most emerging technologies, the specific mechanisms of action are not well understood nor are the specific target cells identified. Patient-related outcomes were typically not addressed in the literature. Numerous recommendations can be made for future research priorities for both basic science and clinical application of emerging therapies. The need to emphasize the importance of regeneration of a functional periodontal organ system was noted. The predictability and efficacy of outcomes, as well as safety concerns and the cost-to-benefit ratio were also identified as key factors for emerging technologies. Conclusions: A number of technologies appear viable as emerging regenerative approaches for periodontal hard and soft tissue regeneration and are expanding the potential of reconstructing the entire periodontal organ system. The cost-to-benefit ratio and safety issues are important considerations for any new emerging therapies. Clinical Recommendation: At this time, there is insufficient evidence on emerging periodontal regenerative technologies to warrant definitive clinical recommendations.
... In addition, histologic findings showed that LCCtreated sites resembled gingiva rather than alveolar mucosa. [31][32][33][34] This product is not currently available commercially. ...
Article
Full-text available
Focused Clinical Question: What are the indications and clinical applications for gingival augmentation procedures, and what factors guide the choice among treatment options in specific situations? Summary: Although there is still controversy regarding whether there needs to be a minimum amount of attached gingiva to maintain the stability of the gingival margin, prospective and retrospective studies have shown that, in the presence of suboptimal plaque control and clinical inflammation, attachment loss and gingival recession (GR) may result unless a minimum amount of keratinized tissue (KT) and attached gingiva are present. Treatment of mucogingival deformities requires gingival augmentation procedures that address both a functional and esthetic component for the patient. Although free gingival grafts (FGGs) are considered the gold standard for treatment of GR defects to obtain root coverage, augmentation of KT and attached gingiva may be accomplished by FGG or other autogenous grafting options, including the free connective tissue graft, the lateral pedicle graft, and the double papilla technique. In addition, the modified apically repositioned flap can be considered in some instances. Alternatives to autogenous graft tissue include acellular dermal matrix, extracellular matrix membrane, bilayer collagen matrix, and living cellular construct. Conclusions: Understanding the clinical importance of the presence of a minimum amount of attached gingiva in patients with suboptimal hygiene is an important first step in addressing the condition. Patient education to address plaque control and counseling to quit smoking in patients who are smokers help enhance the success of these mucogingival surgical procedures. An analysis of patient-specific factors will help with the appropriate choice of surgical procedures aimed at augmenting the dimension of KT/attached gingival tissue. Evidence supporting the treatment decisions described in this practical application is summarized in the companion papers from the American Academy of Periodontology Regeneration Workshop (Kim and Neiva, J Periodontol 2015;86(Suppl.):S56-S72; Scheyer et al., J Periodontol 2015;86(Suppl.):S73-S76).
... In addition, histologic findings showed that LCCtreated sites resembled gingiva rather than alveolar mucosa. [31][32][33][34] This product is not currently available commercially. ...
Article
Full-text available
Gingival augmentation procedures around natural teeth and dental implants are performed to facilitate plaque control, to improve patient comfort, to prevent future recession, and in conjunction with restorative, orthodontic, or prosthetic dentistry. The aim of this study is to answer the most common questions related to this treatment modality based on the most relevant and current knowledge in the field. Two reviewers worked to answer the five most common and clinically relevant questions with supporting literature to understand the role of gingiva around teeth. 1) What circumstances require an increased zone of keratinized tissue (KT), or is KT important? 2) What is the ideal thickness of an autogenous gingival graft? Is a thick autogenous gingival graft more effective than a thin autogenous gingival graft? 3) What are the alternatives to autogenous gingival grafting to increase the zone of attached gingiva? 4) Does orthodontic intervention affect soft tissue health and dimensions? 5) What is the patient-reported patient outcome for minimal KT compared with that for an enhanced zone of KT? An extensive literature search was performed using PubMed, the Cochrane Oral Health Group Specialized Trials Registry (the Cochrane Library), and the most respected journals in the field. Although gingival augmentation procedures were first introduced in 1960s, there have not been in-depth comparative studies examining the five questions that have been proposed by the authors. Lack of relevant systematic reviews and randomized clinical trials (RCTs) on this topic do not allow authors to answer those questions with a strong level of evidence. However, the following can be recommended after reviewing case reports and case series on these topics. 1) There is enough clinical evidence to support maintaining an adequate band of gingiva for intracrevicular margin restoration. 2) Thick grafts do not appear to result in better clinical outcomes than thin grafts. Thick grafts are likely to result in more primary contraction, whereas thin grafts tend to be prone to secondary contraction. 3) Viable alternative treatment modalities are currently available that are capable of providing KT augmentation without the need for palatal donor tissue. 4) Appropriately applied orthodontic forces do not cause permanent damage to a healthy periodontium. The probability of recession during tooth movement in thin biotype is high to justify gingival augmentation when the dimension of gingiva is inadequate. In addition, cases in which there will be a facial tooth movement outside of the alveolar process need to be considered for a gingival augmentation procedure. 5) Although the articles that have been published on this topic did not consider patient-reported outcomes and esthetics as part of the overall treatment success assessment, patients who have received alternative treatment modalities that did not depend on palatal tissue harvesting appear to have reported more satisfaction and less discomfort after treatment. Autogenous gingival grafts are still considered to be the "gold standard" procedure with unmatched success rates and clinical success when gingival augmentation procedures are required. However, tissue-engineered materials may offer viable options to palatal tissue harvesting for gingival augmentation. KT augmentation may prevent the development and progression of gingival recession, especially when restorative margins may interact with the periodontium and/or orthodontic treatment is indicated. Patient-reported outcomes should be considered for future studies on this topic. Additional RCTs and systematic reviews are needed to support these conclusions.
... 17 Hence, stem cell therapy has been utilized more widely for enhancing tissue regeneration, as it promotes formation of both hard and soft tissues. [18][19][20] Stem cells can be harvested from different sources, including bone marrow, fat tissue, dental pulp, or PDL, and recent work in this area has focused on the use of pluripotent stem cells (iPSCs), bone repair cells (also termed ixmyelocel-T), and periosteum-derived cells to induce tissue regeneration. ...
Article
Periodontitis affects nearly half of the adult population in the United States and leads to periodontium destruction, tooth loss, and tooth mobility. Novel bioengineering has become an area of interest in dentistry, as various approaches aim to regenerate attachment apparatus around diseased teeth with the use of barriers, scaffolds, bone grafts, or biologics. This article emphasizes recent findings in the fields of stem cell/gene therapy, 3-dimensional printing, and innovative scaffold designs for future applications in clinical care.
... This material has been used as a substitute for FGG for the treatment of gingival recession defects, where root coverage is not required. In a randomized controlled trial, comparing LCC to FGG [73], results have shown more keratinized gingiva generated by FGG (mean 4.5 mm) than LCC (mean 3.2 mm). LCC regenerated keratinized gingiva of 2 mm or more in 95.3% of the patients. ...
Chapter
Mucogingival deficiencies often pose both esthetic and functional problems. Untreated gingival recession has been demonstrated to progress over time, while its treatment leads to stable root coverage. A variety of therapeutic approaches have been utilized over the years to treat gingival recession defects with each having advantages and disadvantages. The present chapter reviews mucogingival defects, their prevalence, etiologies, classification, and risk assessment. The rationale for gingival recession therapy will be discussed. The variety of therapeutic options and graft materials available will be reviewed, as well as the advantages and disadvantages of each approach. An evidence-based strategy to the treatment of gingival recession entails consideration of risk factors, patient expectations, operator experience, and preferences in order select an appropriate technique, material, and protocol that suits a given patient and clinical scenario.
... Cada día es más frecuente observar la preocupación de los pacientes por este tipo de trastorno, y dentro de estos, uno de los más comunes es la recesión periodontal (RP). (1) Guinard y Caffesse (2) en 1978, la definieron como el desplazamiento del tejido gingival marginal hacia la zona apical del límite amelocementario, dando lugar a la exposición de la superficie radicular pudiendo afectar a uno o varios dientes. Presenta una alta prevalencia a nivel mundial y su incidencia varía del 8 % en niños y jóvenes hasta el 100 % en personas mayores de 50 años. ...
Article
It is more and more frequent to observe the patients concern for the presence of mucous-gingival disorders, and among them, one of the most common is the periodontal recession. It can be accompanied by radicular sensibility, higher prevalence of caries and cervical abrasions. Nevertheless, the aesthetic compromise uses to be the main motive of consultation. In the presence of this kind of disorder we have two possibilities: no treating it and controlling its evolution or correcting it using mucous-gingival surgery techniques. With the objective of showing the behavior of the mucous-gingival disorders and their treatment, we carried out a an observational, descriptive and transversal research in a population of 169 patients attended in the service of Periodontics of the Teaching Stomatologic Clinic III Congreso del PCC, of Matanzas, in the period between 2008 and 2010. Mucous-gingival disorders were present in 34, 1 %, and the periodontal recession was the most frequent (28,6 %). We concluded that women were the most affected, and the age groups from 15 to 34 and from 35 to 59. Most of the patients referred from the service of Orthodontics were 5 to 11 years old and were under periodontal evolvable control; the free graft of connective tissue and epithelium was the most used mucous-gingival technique in the service.
... 50 However, the use of allogenic cell-delivery approaches has demonstrated significant potential in several human clinical trials to expand the zone of attached and keratinized gingiva through the production of local growth factors at the wound site. [51][52][53][54] A commercial product has been developed that uses cadaver-derived allogenic stem cells for application in local bone repair procedures. 55 Recently, cell transplantation of PDL progenitor cells has demonstrated the potential to form hybrid ligament -implant constructs (Fig. 3). ...
Article
Polypeptide growth factors have demonstrated strong potential to repair defects associated with teeth and dental implants. Over the past two decades, intense research efforts have led to the clinical development of several growth factors or biologic agents, including bone morphogenetic proteins, platelet-derived growth factor, fibroblast growth factors, and enamel matrix proteins. Several of these growth factors are now being used clinically for a variety of applications, such as the promotion of periodontal regeneration, sinus floor augmentation, and root coverage procedures. Although clinical results have been promising and growth factors add another dimension to clinical care, optimization of growth factor targeting approaches to periodontal wounds remains a challenge. Enhancement of growth factor local application to improve bioavailability, bioactivity, and allowance of three-dimensional reconstruction of complex anatomic defects is a goal. This article will highlight developments for growth factor delivery to better stimulate the wound healing response for periodontal and bone regeneration in the maxillofacial region.
... [23][24][25] Therefore, it is not surprising that studies assessing patient-reported outcomes have shown a greater preference toward soft tissue graft substitutes. 26,27 In addition, recent studies have suggested that the xenogeneic collagen matrix may provide comparable outcomes to the connective tissue graft in root coverage procedures and at peri-implant sites. 5,7,[28][29][30] Accordingly, the goal of this review was to determine if xenogeneic collagen matrices are viable alternatives to connective tissue graft in peri-implant soft tissue augmentation. ...
Article
Purpose: Several approaches for increasing peri-implant mucosal thickness have been proposed, including autogenous, allogeneic, and xenogeneic grafts. The objective of this meta-analysis was to analyze whether xenogeneic matrices are viable alternatives to autogenous soft tissue grafts in peri-implant soft tissue augmentation. Materials and methods: A systematic search was performed to select randomized clinical trials that compared connective tissue grafts and xenogeneic collagen matrices. The primary outcomes were the mucosal thickness and keratinized mucosa changes, while the secondary outcomes were patient morbidity, painkiller consumption, and surgical time required for the procedure. Results: Seven randomized clinical trials were included for the final evaluation with a total number of 218 implant sites (108 in the connective tissue graft group, 110 in the collagen matrix group) with 3 to 12 months (mean: 6 months) follow-up period. Results showed mucosal thickness increase in both buccal and crestal sites, but it did not yield statistical significance. The keratinized mucosa gain difference was only -0.06 mm (95% CI [-30.0, 0.18]) between the treatments. The postsurgical discomfort, increased consumption of painkillers, and reduction of treatment time (15.46 minutes less) differed significantly in favor of the collagen matrix group. Conclusion: Within the limits of this study, it can be concluded that collagen matrix and connective tissue graft are equivalent in peri-implant soft tissue augmentation.
... 11,67 In this scenario, it is not surprising that studies using subjective-reported qualitative measures have shown patient preference toward approaches avoiding the harvesting of tissue from a second surgical site. 61, 68 Similarly, clinicians have demonstrated increased interest in graft substitutes, such as ADM 69,70 or collagen matrix. 62,71 ...
Article
This state‐of‐the‐art review presents the latest evidence and the current status of autogenous soft tissue grafting for soft tissue augmentation and recession coverage at teeth and dental implant sites. The indications and predictability of the free gingival graft (FGG) and connective tissue graft (CTG) techniques are highlighted, together with their expected clinical and esthetic outcomes. CTG can be harvested from the maxillary tuberosity or from palate with different approaches that can have an impact on graft quality and patient morbidity. The influence of CTG on soft tissue thickness and keratinized tissue width are also discussed. This article is protected by copyright. All rights reserved
... Living cellular constructs (LCS) are 0.75-mm-thick grafts composed of allogenic keratinocytes, fibroblasts, extracellular matrix proteins, and bovine collagen, 74,93 delivered on a semipermeable polycarbonate membrane on an agarose-rich nutrient medium. 94 Histologically and clinically, LCStreated sites resemble gingiva resulting in a site- appropriate color matching tissue, absence of scar formation, and a mucogingival junction alignment. They achieve inferior KT gain with superior esthetics and patient satisfaction than FGG. ...
Article
The presence of healthy soft tissue at the tooth and implant interface correlates to long-term success and stability in function and esthetics. Grafting procedures utilizing various techniques can be performed during any stage of the implant or restorative therapy. Materials of autogenous, allogeneic, and xenogeneic sources are available for oral soft tissue grafting. This article describes the classifications of soft tissue defects, treatment modalities, and materials used to enhance soft tissue quality and quantity and to achieve optimal esthetics and function around teeth and implants.
... Techniques that use stem cells to reconstruct oral soft tissue show promising results [15][16][17][18][19]; however, they are financially costly and require more documented cases for clinical application [8]. At present, probable alternatives are regenerative techniques that use acellular matrices. ...
Article
Full-text available
his research aims to evaluate the clinical and histological parametric differences concern-ing keratinized tissue that result from two regeneration techniques, the subepithelial autologous connective tissue graft (ACTG) and the acellular dermal matrix (MD) of porcine origin, performed on surgical beds on edentulous spaces in an animal model. The parameters of the MD and ACTG groups were compared with samples of the control group (CG) after 15, 45, and 90 days. Nine female white pigs (Sus scrofa domestica) were used, and each animal provided 20 study areas (12 MD and 8 ACTG). At 15 days, the keratin layer thickness in the MD group was greater than those of the ACTG (25.27 vs. 19.95 μm) and the CG (21.2 μm). After 45 days, the MD and ACTG thickness values de- creased but were higher than the CG. At 90 days, MD (19.46 μm) obtained a value close to that of CG, and the ACTG decreased to CG (15.53 μm, p < 0.001). The use of an MD may be a viable alter-native to the ACTG because of its ability to provide increased keratinized tissue in comparison to the ACTG.
... In terms of skin burns, the product packaging insert for Kaloderm stated that, no adverse reaction has been reported other than a possible occasional infection at the site, dermatitis, exudate formation, weak edema, hypersensitivity, and pain. In addition, Kaloderm can promote the re-epithelialization of deep abdominal cavity burns (McGuire et al., 2011;You et al., 2012). ...
Article
Full-text available
The introduction of advanced therapy medicinal products (ATMPs) to the global pharma market has been revolutionizing the pharmaceutical industry and has opened new routes for treating various types of cancers and incurable diseases. In the past two decades, a noticeable part of clinical practices has been devoting progressively to these products. The first step to develop such an ATMP product is to be familiar with other approved products to obtain a general view about this industry trend. The present paper depicts an overall perspective of approved ATMPs in different countries, while reflecting the degree of their success in a clinical point of view and highlighting their main safety issues and also related market size as a whole. In this regard, published articles regarding safety, efficacy, and market size of approved ATMPs were reviewed using the search engines PubMed, Scopus, and Google Scholar. For some products which the related papers were not available, data on the relevant company website were referenced. In this descriptive study, we have introduced and classified approved cell, gene, and tissue engineering-based products by different regulatory agencies, along with their characteristics, manufacturer, indication, approval date, related regulatory agency, dosage, product description, price and published data about their safety and efficacy. In addition, to gain insights about the commercial situation of each product, we have gathered accessible sale reports and market size information that pertain to some of these products.
... Because of the similarities of healing between cutaneous and oral mucosa wounds, it was thought that a skin substitute may deliver better results than the standard free gingival graft in terms of the color and texture of the gingiva while providing an adequate amount of new keratinized gingiva. A series of studies evaluating Apligraf ® as a tissue substitute to augment the width of keratinized gingiva were carried out and they showed that the graft was safe and able to produce keratinized gingiva although not as much as the free gingival graft [135][136][137]. In 2012, the US-FDA authorized Organogenesis, the company manufacturing Apligraf ® , to market this product as Gintiut ® to treat mucogingival conditions [133]. ...
Chapter
Full-text available
A main challenge for soft tissue regeneration is to develop products and therapies that minimize the fibrotic scarring characteristic of tissue repair. Scaffolds are three-dimensional structures in which cells can attach, grow and differentiate to form ex vivo or in vivo artificial tissue. They provide signals that trigger cell migration from the wound bed, as well as cell differentiation and cell secretion of extracellular matrix constituents. Scaffolds are made of natural or synthetic materials, with proteins from the collagen family being among the most used natural polymers. Collagen type I is a major component of the complex extracellular network of proteins that form the matrix of mammal tissues. Besides having cell-binding sequences, this protein is biodegradable, biocompatible, and exhibits a haemostatic effect when placed in open wounds. The aforementioned properties have made this compound a widely used natural material to produce scaffolds for tissue engineering skin and oral mucosa substitutes. This chapter reviews some of the parameters that influence the bioactivity of scaffolds emphasizing on collagen I scaffolds and their major applications in soft tissue engineering.
... 37,38 Recently, 3D, skin-like tissues have been approved for clinical use in the treatment of periodontal disease. 39 Levenberg et al. first established proof-ofconcept that ectodermal and mesenchymal cells differentiated from hESCs could assemble into tissues displaying in vivo-like features and could integrate into the host vasculature. 40 In addition, tissues that show fully-mature, functional skin upon engraftment to mice have been engineered from hESC-derived keratinocytes. ...
Article
Significance: Human-induced pluripotent stem cells (iPSC) can be differentiated into patient-specific cells with a wide spectrum of cellular phenotypes and offer an alternative source of autologous cells for therapeutic use. Recent studies have shown that iPSC-derived fibroblasts display enhanced cellular functions suggesting that iPSC may eventually become an important source of stem cells for regenerative therapies. Recent Advances: The discovery of approaches to reprogram somatic cells into pluripotent cells opens exciting avenues for their use in personalized, regenerative therapies. The controlled differentiation of functional cell types from iPSC provides a replenishing source of fibroblasts. There is intriguing evidence that iPSC reprogramming and subsequent differentiation to fibroblast lineages may improve cellular functional properties. Augmenting the biological potency of iPSC-derived fibroblasts may enable the development of novel, personalized stem cell therapies to treat oral disease. Critical Issues: Numerous questions need to be addressed before iPSC-derived cells can be used as a practical oral therapy. This will include understanding why iPSC-derived cells are predisposed towards differentiation pathways along lineages related to their cell of origin, screening iPSC-derived cells to ensure their safety and phenotypic stability and developing engineered, three-dimensional tissue models to optimize their function and efficacy for future therapeutic transplantation. Future Directions: Future research will need to address how to develop efficient methods to deliver and integrate iPSC-derived fibroblasts into the oral mucosa. This will require an improved understanding of how to harness their biological potency for regenerative therapies that are specifically targeted to the oral mucosa.
Article
Full-text available
Purpose: The purpose of this clinical guidelines project was to determine the most appropriate surgical techniques, in terms of efficacy, complications, and patient opinions, for the treatment of buccal single gingival recessions without loss of interproximal soft and hard tissues. Methods: Literature searches were performed (electronically and manually) for entries up to 28 February, 2013 concerning the surgical approaches for the treatment of gingival recessions. Systematic reviews (SRs) of randomised controlled trials (RCTs) and individual RCTs that reported at least 6 months of follow-up of surgical treatment of single gingival recessions were included. The full texts of the selected SRs and RCTs were analysed using checklists for qualitative evaluation according to the Scottish Intercollegiate Guidelines Network (SIGN) method. The following variables were evaluated: Complete Root Coverage (CRC); Recession Reduction (RecRed); complications; functional and aesthetic satisfaction of the patients; and costs of therapies. Results: Out of 30 systematic reviews, 3 SRs and 16 out of 313 RCTs were judged to have a low risk for bias (SIGN code: 1+). At a short-term evaluation, the coronally advanced flap plus connective tissue graft method (CAF+CTG) resulted in the best treatment in terms of CRC and/or RecRed; in case of cervical abrasion and presence of root sensitivity CAF + CTG + Restoration caused less sensitivity than CAF+CTG. CAF produced less postoperative discomfort for patients. Limited information is available regarding postoperative dental hypersensitivity and aesthetic satisfaction of the patients. Conclusion: In presence of aesthetic demands or tooth hypersensitivity, the best way to surgically treat single gingival recessions without loss of interproximal tissues is achieved using the CAF procedure associated with CTG. Considering postoperative discomfort, the CAF procedure is the less painful surgical approach, while the level of aesthetic satisfaction resulted higher after CAF either alone or with CTG. It is unclear how much tooth hypersensitivity is reduced by surgically covering buccal recessions. It is important to note that the present recommendations are based on short-term data (less than 1 year).
Article
Gingiva of the oral mucosa provides a practical source to isolate fibroblasts for therapeutic purposes because the tissue is easily accessible, tissue discards are common during routine clinical procedures and wound healing after biopsy is fast and results in complete wound regeneration with very little morbidity or scarring. In addition, gingival fibroblasts have unique traits, including neural crest origin, distinct gene expression and synthetic properties and potent immunomodulatory functions. These characteristics may provide advantages for certain therapeutic approaches over other more commonly used cells, including skin fibroblasts, both in intraoral and extra-oral sites. However, identity and phenotype of gingival fibroblasts, like other fibroblasts, are still not completely understood. Gingival fibroblasts are phenotypically heterogeneous, and these…fibroblast subpopulations may play different roles in tissue maintenance, regeneration and pathologies. The purpose of this review is to summarize what is currently known about gingival fibroblasts, their distinct potential for tissue regeneration and their potential therapeutic uses in the future.
Article
Background: The standard of care for increasing keratinized tissue (KT) and vestibular area is an autogenous free gingival graft (FGG) and vestibuloplasty; however, there is morbidity associated with the harvest of autogenous tissue, and supply is limited. The purpose of this study is to determine if a xenogeneic collagen matrix (CM) might be as effective as FGG. Methods: This study is a single-masked, randomized, controlled, split-mouth study of 30 patients with insufficient zones of KT (<2 mm). It uses a within-patient treatment-comparison design to establish non-inferiority of the test (CM) versus control (FGG) therapy. The primary efficacy endpoint was change in KT width (∆KT) from surgery to 6 months post-surgery. Secondary endpoints included traditional periodontal measures, such as clinical attachment level, recession, and bleeding on probing. Patient-reported pain, discomfort, and esthetic satisfaction were also recorded. Biopsies were obtained at 6 months. Results: Surgery and postoperative sequelae were uneventful, with normal healing observed at both test and control sites. The primary outcome, ∆KT width at 6 months, did not establish non-inferiority of CM compared to FGG (P = 0.9992), with the FGG sites averaging 1.5 mm more KT width than CM sites. However, the amount of new KT generated for both therapies averaged ≥2 mm. Secondary outcomes were not significantly different between test and control sites. All site biopsies appeared as normal mucoperiosteum with keratinized epithelium. CM sites achieved better texture and color matches, and more than two-thirds of patients preferred the appearance of their CM sites. Conclusion: With the proviso of sufficient KT (≈2 mm in width) and study goals of lower morbidity, unlimited supply, and patient satisfaction, CM appears to be a suitable substitute for FGG in vestibuloplasty procedures designed to increase KT around teeth.
Article
The authors review patient reported outcome (PRO) metrics for dentistry, and in particular, Periodontics. The PROs commentary for Periodontics includes a review of a split mouth, randomized, controlled clinical trial results that specifically tracked pain at different sites over time following intervention, provided guidelines for peak pain time points and evidence for referred pain assessment when studying soft tissue augmentation procedures. Both the questions that are asked of patients and the timing of those questions are important study design considerations. The authors suggest PROs methodology for periodontal clinical trials that can be used to identify information important to patients and clinicians.
Article
Periodontitis, a recognized disease worldwide, is bacterial infection-induced inflammation of the periodontal tissues that results in loss of alveolar bone. Once it occurs, damaged tissue cannot be restored to its original form, even if decontaminating treatments are performed. For more than half a century, studies have been conducted to investigate true periodontal regeneration. Periodontal regeneration is the complete reconstruction of the damaged attachment apparatus, which contains both hard tissue (alveolar bone and cementum) and soft tissue (periodontal ligament). Several treatments, including bone grafts, guided tissue regeneration with physical barriers for epithelial cells, and growth factors have been approved for clinical use; however, their indications and outcomes are limited. To overcome these limitations, the concept of "tissue engineering" was introduced. Combination treatment using cells, growth factors, and scaffolds, has been studied in experimental animal models, and some studies have been translated into clinical trials. In this review, we focus on recent progressive tissue engineering studies and discuss future perspectives on periodontal regeneration. Anat Rec, 297:16-25. 2014. © 2013 Wiley Periodicals, Inc.
Article
Generation of site-appropriate tissue in the oral cavity includes the restoration of the correct anatomical type, amount, and distribution of the tissue. This study is a post-hoc analysis of data collected during previously published results from two randomized clinical trials of a living cellular sheet (LCS; allogeneic cultured keratinocytes and fibroblasts in bovine collagen) versus a free gingival graft (FGG) evaluating their ability to augment keratinized tissue (KT) or gingiva. Post-hoc histological and clinical (photographic) comparisons of the outcomes of treatment were performed on histologic and photographic data gathered in the two randomized clinical trials. Histological findings showed that LCS-treated sites resembled gingiva rather than alveolar mucosa. Photographic analysis indicated that LCS treatment resulted in more site-appropriate tissue than FGG in terms of tissue color with adjacent untreated tissue, absence of scar formation or keloid-like appearance, and mucogingival junction (MGJ) alignment. Treatment of mucogingival defects with LCS resulted in the generation of tissue that is more site-appropriate than tissue transplanted from the palate.
Article
Full-text available
Objectives The present systematic review compared the effectiveness of soft tissue substitutes (STSs) and autogenous free gingival grafts (FGGs) in non-root-coverage procedures to increase keratinized tissue (KT) width around teeth. Materials and methodsIncluded studies fulfilled the following main eligibility criteria: (a) preclinical in vivo or human controlled trials using FGG as control, (b) non-root-coverage procedures, and (c) assessment of KT width. Meta-analysis was performed on the gain in KT width (primary outcome variable) and several secondary variables. ResultsEight human trials with short observation time evaluating five different STSs were identified. FGG yielded consistently significantly (p < 0.001) larger increase in KT width irrespective whether the comparison regarded an acellular matrix or a tissue-engineered STS. Further, FGG yielded consistently ≥2 mm KT width postoperatively, while use of STS did not, in the few studies reporting on this outcome. On the other hand, STSs resulted in significantly better aesthetic outcomes and received greater patient preference (p < 0.001). Conclusions Based on relatively limited evidence, in non-root-coverage procedures, FGG (1) resulted consistently in significantly larger increase in KT width compared to STS and (2) yielded consistently ≥2 mm KT width postoperatively, while STSs did not. STSs yielded significantly better aesthetic outcomes, received greater patient preference, and appeared safe. Clinical relevanceLarger and more predictable increase in KT width is achieved with FGG, but STSs may be considered when aesthetics is important. Clinical studies reporting relevant posttreatment outcomes, e.g., postop KT width ≥2 mm, on the long-term (>6 months) are warranted.
Article
More than 30 years have passed since the first successful application of regenerative therapy for treatment of periodontal diseases. Despite being feasible, periodontal regeneration still faces numerous challenges, and complete restoration of structure and function of the diseased periodontium is often considered an unpredictable task. This review highlights developing basic science and technologies for potential application to achieve reconstruction of the periodontium. A comprehensive search of the electronic bibliographic database PubMed was conducted to identify different emerging therapeutic approaches reported to influence either biologic pathways and/or tissues involved in periodontal regeneration. Each citation was assessed based on its abstract, and the full text of potentially eligible reports was retrieved. Based on the review of the full papers, their suitability for inclusion in this report was determined. In principle, only reports from scientifically well-designed studies that presented preclinical in vivo (animal studies) or clinical (human studies) evidence for successful periodontal regeneration were included. Hence, in vitro studies, namely those conducted in laboratories without any live animals, were excluded. In case of especially recent and relevant reviews with a narrow focus on specific regenerative approaches, they were identified as such, and thereby the option of referring to them to summarize the status of a specific approach, in addition to or instead of listing each separately, was preserved. Admittedly, the presence of subjectivity in the selection of studies to include in this overview cannot be excluded. However, it is believed that the contemporary approaches described in this review collectively represent the current efforts that have reported preclinical or clinical methods to successfully enhance regeneration of the periodontium. Today's challenges facing periodontal regenerative therapy continue to stimulate important research and clinical development, which, in turn, shapes the current concept of periodontal tissue engineering. Emerging technologies-such as stem cell therapy, bone anabolic agents, genetic approaches, and nanomaterials-also offer unique opportunities to enhance the predictability of current regenerative surgical approaches and inspire development of novel treatment strategies.
Article
Full-text available
Large areas of mucogingival alterations may result from advanced regenerative procedures. This prospective case series study was performed to introduce and evaluate a surgical approach that combines the strip gingival graft technique with the use of a xenogeneic collagen matrix. The primary outcome measurement was the increase in keratinized tissue width from baseline to 12 months postprocedure. Twenty patients were enrolled, and they all completed the 12-month evaluation. All treated sites exhibited a significant gain in keratinized tissue at 12 months, with a mean width of 6.33 mm (SD: 2.16), while there was a 43% contraction of the grafted area at 6 months. Tissue dimensions remained stable between 6 and 12 months. The use of the combination graft was well accepted by the patients, with minimal morbidity according to the patients' low self-reported pain and the low utilization of pain medication.
Article
Peri-implant soft tissues and their management have become increasingly important in the last few years. In terms of the significance of peri-implant soft tissues on the health and inflammatory state of implants, a slight trend has emerged in the literature that recommends sufficient dimensions (> 2 mm width) of keratinized peri-implant soft tissues. This article reviews the literature on the controversy surrounding keratinized peri-implant soft tissues and summarizes the current scientific evidence on soft tissue augmentation, specifically techniques for the creation and/or broadening of keratinized peri-implant soft tissues and for increased volume with autologous tissue grafts. Common alternatives are presented and discussed based on scientific data and clinical case scenarios.
Article
Full-text available
The objective of this study was to evaluate the clinical effectiveness of platelet-rich fibrin (PRF) membrane used in combination with a modified coronally advanced flap (MCAF) and to compare it with the use of a subepithelial connective tissue graft (SCTG) in combination with a MCAF in treatment of Miller Class I and II bilateral multiple gingival recessions. A total of 20 patients with multiple Miller Class I and II maxillary gingival recession defects participated in this randomized, split-mouth, controlled study. A total of 60 defects received either PRF + MCAF (test group, n = 30) or MCAF with SCTG (control group, n = 30). Gingival recession depth (RD), keratinized tissue width (KTW), probing depth (PD), clinical attachment level (CAL), and gingival thickness (GT) were evaluated at baseline and after 6 months. Patients' discomfort postsurgery was measured by comparing visual analog scale scores. The percentage of root coverage was 84% in the control group and 77.12% in the test group (P = .007). Complete root coverage of the control and test groups was 60% and 50%, respectively (P = .112). KTW and GT increased in both groups from baseline to 6 months (P < .001). At 6 months postoperative, KTW was greater in the control group (P = .024) and GT was higher in the test group (P = .005). Use of a PRF membrane in gingival recession treatment decreased postoperative discomfort compared to SCTG-treated gingival recessions (P < .001). Within the limitations of the present study, it was concluded that localized gingival recessions could be successfully treated with MCAF + PRF as well as MCAF + SCTG. The PRF technique has the bonus advantage of being more comfortable during the postoperative period. The author suggests that the use of PRF is a valid alternative to SCTG for the treatment of localized gingival recessions.
Article
The objective of this study was to evaluate the clinical effectiveness of platelet-rich fibrin (PRF) membrane used in combination with a modified coronally advanced flap (MCAF) and to compare it with the use of a subepithelial connective tissue graft (SCTG) in combination with a MCAF in treatment of Miller Class I and II bilateral multiple gingival recessions. A total of 20 patients with multiple Miller Class I and II maxillary gingival recession defects participated in this randomized, split-mouth, controlled study. A total of 60 defects received either PRF + MCAF (test group, n = 30) or MCAF with SCTG (control group, n = 30). Gingival recession depth (RD), keratinized tissue width (KTW), probing depth (PD), clinical attachment level (CAL), and gingival thickness (GT) were evaluated at baseline and after 6 months. Patients' discomfort postsurgery was measured by comparing visual analog scale scores. The percentage of root coverage was 84% in the control group and 77.12% in the test group (P = .007). Complete root coverage of the control and test groups was 60% and 50%, respectively (P = .112). KTW and GT increased in both groups from baseline to 6 months (P < .001). At 6 months postoperative, KTW was greater in the control group (P = .024) and GT was higher in the test group (P = .005). Use of a PRF membrane in gingival recession treatment decreased postoperative discomfort compared to SCTG-treated gingival recessions (P < .001). Within the limitations of the present study, it was concluded that localized gingival recessions could be successfully treated with MCAF + PRF as well as MCAF + SCTG. The PRF technique has the bonus advantage of being more comfortable during the postoperative period. The author suggests that the use of PRF is a valid alternative to SCTG for the treatment of localized gingival recessions.
Article
The main purposes of periodontal graft surgery include achieving root coverage, improving the clinical attachment level and keratinized tissue, and advancing the procedure of periodontal plastic surgery. Autogenous graft, such as subepithelial connective tissue graft-based procedure, provide the best outcomes for mean and complete root coverage, as well as increase in keratinized tissue. However, a disadvantage of the procedure is in the location of the operation itself: the additional surgical site (palate). Therefore, clinicians are always looking for graft substitutes. This article will discuss the evidence supporting the use of 1) acellular dermal matrix (ADM); 2) xenogeneic collagen matrix (XCM); 3) recombinant human platelet-derived growth factor (rhPDGF); 4) enamel matrix derivative (EMD); 5) guided tissue regeneration (GTR); 6) living cellular construct (LCC), all of which are used in conjunction with coronally advanced flaps as alternatives to autogenous donor tissue. The decision tree for treatments of Miller recession-type defects are also discussed.
Article
Full-text available
Background and Aim Human gingival fibroblasts cultured on collagen membrane as an alternative treatment method used in tissue regeneration can lead to improved results in root coverage. The aim of this study was to evaluate the human gingival fibroblast proliferation and adhesion cultured on three types of collagen membranes. Materials and Methods In this in vitro study, first-line human gingival fibroblast cells (HGF1-RT1) prepared and cultured on three membranes, including porcine pericardium (PP) (Jason, Botiss dental), human pericardium (HP) (Regen, Faravardeh Baft Iranian), and glutaraldehyde cross-linked (GC) (BioMend Extend, Zimmer Dental). Cell survival was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) after 24, 48, and 72 h and 7 days. Furthermore, morphology and adhesion of cells on the membrane were evaluated after 1 and 7 days by electron microscopy (scanning electron microscopy [SEM]). Statistical analysis was performed using two-way ANOVA with a significance level of 0.05. Results Based on the results of MTT, cell survival on HP and PP membranes after 7 days significantly increased (P < 0.001), but for the GC membrane, it was reduced after 7 days (P = 0.031). Cell survival on HP and PP membranes did not differ (P = 1) and was more than GC (P < 0.001). SEM images showed that the adhesion of cells was better on HP and PP membranes than GC. Conclusion The results of this study showed that natural collagen membranes (HP and PP) similarly support proliferation and adhesion of gingival fibroblasts. Survival and adhesion of gingival fibroblasts on cross-linked collagen membrane was less than two other membranes.
Chapter
Periodontal diseases have become exceedingly widespread, and management of the defects due to periodontitis has been a great challenge in periodontal therapies. In the last two decades, concerted efforts have aimed to improve periodontal tissue regeneration by bone grafting and guided tissue regeneration. Recent studies have focused on tissue engineering (TE) techniques for periodontal regeneration using stem cells, growth factors, and scaffolds to grow new functional tissues, rather than building replacements for lost periodontal tissues. The future of periodontal regeneration research requires an understanding of current findings, which in turn highlights the need for future research. In this chapter, we review recent progress in periodontal tissue regeneration and current tissue engineering approaches. The advantages and disadvantages of this method in clinical practice will be also discussed based on recent studies.
Chapter
To fully regenerate the periodontal tissues remains a challenge in our daily practice. Periodontal regeneration is a complex process involving a series of cellular and molecular events. In the last two decades, significant advances have been made in applying proteins and peptides to treat periodontal osseous defects. Several products are currently available and a few others are under development. Stem cell therapy has also been vigorously investigated for regenerating craniofacial tissues including periodontia. In this chapter, we review the current status of protein- and cell-based therapies for periodontal regeneration, with an emphasis on products that have been tested in clinical studies.
Article
Full-text available
Objectives: This study aimed to evaluate the mucograft collagen matrix (CM) to increase keratinized tissue around teeth compared to free gingival graft (FGG). Materials and Methods: The present double-blind, randomized, controlled clinical trial studied 12 patients who had 2 mm or less keratinized gingiva bilaterally around mandibular premolars. The 6-month width of keratinized tissue, periodontal parameters (preoperatively and 1, 3, and 6 months postoperatively), color match, pain, and total surgical time were measured. Results: The mean dimensional change of keratinized gingiva 6 months postoperatively was 4.1±0.7 mm for FGG and 8±1.7 mm for CM. Periodontal parameters were not affected in the two groups. The CM group had a significantly lower pain, experienced less surgery time, and gained better aesthetics compared to the FGG group. Conclusion: CM appears to be a suitable substitute for FGG in procedures designed to increase keratinized tissue around teeth. It has remarkable benefits, such as acceptable keratinized tissue gain, less pain, less surgical chair time, and better aesthetics.
Article
Full-text available
Purpose of Review Alveolar boundaries dictate the limitations of orthodontic tooth movement. Evaluation of the hard and soft tissues in terms of quality and quantity in conjunction with a sound orthodontic treatment plan that includes the amount and direction of desired tooth movement is essential. Prophylactic intervention may be required to support orthodontic goals and objectives without undesired iatrogenic periodontal consequences. The purpose of this article is to provide a review on current methods utilized for augmentation procedures prior to orthodontic treatment. Recent Findings Orthodontic treatment can have a significant impact on periodontal health. Increased demands by patients for non-extraction treatment and for camouflaged treatment of skeletal discrepancies to avoid orthognathic surgery can place challenges on orthodontists. Dental arch expansion and placing teeth beyond biologically acceptable limits can result in unfavorable periodontal outcomes, such as the development of fenestrations and dehiscences. Summary Phenotype modification therapy via soft and/or hard tissue augmentation may expand the range of orthodontic movement without the risk of undesired periodontal outcomes during orthodontic treatment.
Chapter
Full-text available
Developments in engineering and biological science technologies in recent years have increased the capacity of tissue engineering to be utilized in medical and dental disciplines more effectively. Numerous studies have been conducted using stem cells and scaffolding materials to investigate the potential of regenerative periodontal procedures. The scope of this chapter is to review the nature of periodontal regeneration, the current understanding of periodontal regenerative protocols and surgical applications, recent developments in periodontal tissue engineering, variables that affect clinical applications of periodontal regeneration, and to discuss the limitations and the future directions of regenerative periodontal research.
Article
Periodontitis is a inflammation induced by a bacterial infection that causes the destruction of the attachment apparatus of dental roots. Several materials, such as bone graft materials, barrier membranes and protein products have been developed and used to treat periodontal defects clinically; however, it is difficult to regenerate the complete periodontal tissue structure. Recently, cytotherapeutic approaches have been introduced to overcome the limitation of conventional procedures. The in vitro-expanded autologous cells derived from several kinds of tissues have already been used in several clinical trials. These cytotherapeutic treatments have been shown to be safe and effective for the treatment of periodontitis. Our strategy has been to integrate stem cell biology and cell sheet engineering, in which a temperature-responsive intelligent polymer is grafted onto the surface of cell culture dish to create a 'cell sheet', to achieve a novel treatment method for periodontitis. By simple reduction of the temperature to below 32°C, a contiguous cell sheet, which is capable of keeping extracellular matrix proteins and cell-cell interactions intact, can be harvested for transplantation without the use of scaffolds. This technology has already been employed in clinical trials, confirming the safety and efficacy of the treatment. In this review, we introduce recent progress in the engineering of cell sheets and review the potential of cell sheet technology for periodontal regenerative medicine. Copyright © 2013 John Wiley & Sons, Ltd.
Article
Full-text available
The use of intra-oral soft-tissue-engineered devices has demonstrated potential for oral mucosa regeneration. The aim of this study was to investigate the temporal expression of angiogenic biomarkers during wound healing of soft tissue reconstructive procedures comparing living cellular constructs (LCC) with autogenous free gingival grafts. Forty-four human participants bilaterally lacking sufficient zones of attached keratinized gingiva were randomly assigned to soft tissue surgery plus either LCC or autograft. Wound fluid samples were collected at baseline and weeks 1, 2, 3, and 4 post-operatively and analyzed for a panel of angiogenic biomarkers: angiogenin (ANG), angiostatin (ANT), PDGF-BB, VEGF, FGF-2, IL-8, TIMP-1, TIMP-2, GM-CSF, and IP-10. Results demonstrated a significant increase in expression of ANT, PDGF-BB, VEGF, FGF-2, and IL-8 for the LCC group over the autograft group at the early stages of wound repair. Although angiogenic biomarkers were modestly elevated for the LCC group, no clinical correlation with wound healing was found. This human investigation demonstrates that, during early wound-healing events, expression of angiogenic-related biomarkers is up-regulated in sites treated with LCC compared with autogenous free gingival grafts, which may provide a safe and effective alternative for regenerating intra-oral soft tissues (ClinicalTrials.gov number, NCT01134081).
Article
Full-text available
The purpose of this review is to evaluate the effectiveness of different root-coverage procedures in the treatment of recession-type defects. The Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched for entries up to October 2008. There were no restrictions regarding publication status or the language of publication. Only clinical randomized controlled trials (RCTs) with a duration > or = 6 months that evaluated recession areas (Miller Class I or II > or = 3 mm) that were treated by means of periodontal plastic surgery procedures were included. Twenty-four RCTs provided data. Only one trial was considered to be at low risk of bias. The remaining trials were considered to be at high risk of bias. The results indicated a significantly greater reduction in gingival recession and gain in keratinized tissue for subepithelial connective tissue grafts (SCTGs) compared to guided tissue regeneration (GTR) with bioabsorbable membranes (GTR bms). A significantly greater gain in keratinized tissue was found for enamel matrix protein compared to a coronally advanced flap (0.40 mm) and for SCTGs compared to GTR bms plus bone substitutes. Limited data exist on the changes of esthetic conditions as related to the opinions and preferences of patients for specific procedures. SCTGs, coronally advanced flaps alone or associated with other biomaterial, and GTR may be used as root-coverage procedures for the treatment of localized recession-type defects. In cases where root coverage and gain in keratinized tissue are expected, the use of SCTGs seems to be more adequate.
Article
Full-text available
The aim of this retrospective long-term split-mouth study was to compare the periodontal conditions of sites treated with gingival-augmentation procedures to untreated homologous contralateral sites over a long period of time (10 to 27 years). Fifty-five subjects with 73 sites (test group) lacking attached gingiva associated with recessions were treated by means of submarginal free gingival grafts (SMFGGs) and marginal free gingival grafts (MFGGs). The 73 contralateral homologous sites (control group), with or without recession and with or without attached gingiva, were not treated. Patients were recalled every 4 months during the follow-up period (10 to 27 years). Clinical variables, including recession depth, amount of keratinized tissue (KT), and probing depth (PD), were measured in treated and untreated sites at baseline, at 1 year, and at the end of the follow-up period. At the end of the follow-up period, recession was reduced in all treated sites (1.5 +/- 1.0 mm for SMFGG and 1.3 +/- 0.9 mm for MFGG), whereas it was increased in the untreated sites (-0.7 +/- 0.7 mm for SMFGG and -1.0 +/- 0.5 mm for MFGG). In the treated sites, the increased KT remained quite stable during the follow-up period. PD remained stable (1 mm) in the treated and untreated sites. The sites treated with gingival-augmentation surgery showed a tendency for coronal displacement of the gingival margin with a reduction in recession. The contralateral untreated sites showed a tendency for apical displacement of the gingival margin with an increase in the existing recessions.
Article
Full-text available
This study compared the results following treatment of gingival recessions by a coronally advanced flap procedure alone (CAF) or combined with a bioabsorbable membrane and a demineralized xenograft (GTRF). Sixteen nonsmokers with 20 Miller Class I or Class II buccal gingival recessions at canines or premolars were included in the study. Sites were randomly assigned to either CAF treatment (control, n = 10) or GTRF treatment (test, n = 10) and examined at baseline and at 6 months postoperatively. Both treatments resulted in a significant reduction in recession and gain in clinical attachment level; there was no significant difference between treatments. No differences were found in probing depths among or between the groups. The increase in keratinized tissue from baseline to 6 months was slightly greater for the GTRF group than for the CAF group, but without statistical significance. The test group experienced a statistically significant increase in gingival thickness from baseline to the 6-month evaluation, while little gain was detected in the control group; the between-group difference was statistically significant in favor of the test group. Both procedures offer a predictable, simple, and convenient means of root coverage in Miller Class I and II recession defects, but the GTRF-supported procedure resulted in more keratinized tissue and a significant increase in gingival thickness than the CAF-only approach.
Article
Full-text available
We assessed in a randomized prospective trial the effectiveness of Graftskin, a living skin equivalent, in treating noninfected nonischemic chronic plantar diabetic foot ulcers. In 24 centers in the U.S., 208 patients were randomly assigned to ulcer treatment either with Graftskin (112 patients) or saline-moistened gauze (96 patients, control group). Standard state-of-the-art adjunctive therapy, which included extensive surgical debridement and adequate foot off-loading, was provided in both groups. Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks (maximum of five applications) or earlier if complete healing occurred. The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit. At the 12-week follow-up visit, 63 (56%) Graftskin-treated patients achieved complete wound healing compared with 36 (38%) in the control group (P = 0.0042). The Kaplan-Meier median time to complete closure was 65 days for Graftskin, significantly lower than the 90 days observed in the control group (P = 0.0026). The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 (95% CI 1.23-3.74). The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations, both of which were less frequent in the Graftskin group. Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects. Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available standard of care.
Article
Full-text available
The need for keratinized mucosa (KM) or immobile keratinized mucosa (i.e., attached mucosa [AM]) for the maintenance of osseointegrated endosseous dental implants has been controversial. The purpose of this study was to investigate the significance of KM in the maintenance of root-form dental implants with different surfaces. A total of 339 endosseous dental implants in place for at least 3 years in 69 patients were evaluated. The width of KM and AM, modified plaque index (mPI), gingival index (GI), modified bleeding index (mBI), probing depth (PD), and average annual bone loss (ABL) were measured clinically and radiographically by a masked examiner. Based on the amounts of KM or AM, implants were categorized as follows: 1) KM <2 mm (KL); 2) KM > or =2 mm (KU); 3) AM <1 mm (AL); and 4) AM > or =1 mm (AU). Implants were further subdivided into the following four subgroups based on their surface configurations: 1) smooth surface implants (SI) with KM <2 mm (SKL); 2) SI with KM > or =2 mm (SKM); 3) rough surface implants (RI) with KM <2 mm (RKL); or 4) RI with KM > or =2 mm (RKM); or 1) SI with AM <1 mm (SAL); 2) SI with AM > or =1 mm (SAM); 3) RI with AM <1 mm (RAL); or 4) RI with AM > or =1 mm (RAM). The effect of KM or AM on clinical parameters was evaluated by comparing the different KM/AM groups. In addition, the significance of the presence of KM on implant prostheses types (i.e., fixed versus removable) and on implant locations (i.e., anterior versus posterior) was evaluated. Comparison of ABL among the four subgroups in KM or AM failed to reveal statistically significant differences (P >0.05); however, statistically significantly higher GI and mPI were present in SKL or SAL compared to the other three subgroups (P <0.05). GI and mPI were significantly higher in KL (0.94 and 1.51) than KU (0.76 and 1.26) and higher in AL (0.95 and 1.50) than AU (0.70 and 1.19) (P <0.05), respectively. The difference in GI between posterior implants with or without an adequate amount of KM was also significant (P <0.05). The absence of adequate KM or AM in endosseous dental implants, especially in posterior implants, was associated with higher plaque accumulation and gingival inflammation but not with more ABL, regardless of their surface configurations. Randomized controlled clinical trials are needed to confirm the results obtained in this retrospective clinical study.
Article
Full-text available
The shrinkage of free gingival grafts (FGGs) is a well-known clinical phenomenon but there are limited studies demonstrating the dimensional changes during healing in FGGs. The aim of the study is to examine the shrinkage of FGG in both horizontal and vertical dimensions and calculate the changes in the surface area of the graft at early and delayed periods of healing. The FGG procedure was applied to 15 consecutive patients in their mandibular anterior area. The graft sizes and areas were measured and the shrinkage of the graft was calculated at baseline and days 10, 21 and 180. Hemorrhage, sense alteration and pain symptoms were also examined. Change in the horizontal direction was not statistically significant during the whole study period (p > 0.05). However, there was a statistically significant reduction in the vertical direction in all visits, except day 10 (p < 0.05). Calculated graft area was also significantly reduced during the study period at all time-points compared to the baseline (p < 0.001). At day 10, 4 (26.7%) recipient sites and 5 (33%) donor sites demonstrated paresthesia. Only one (0.07%) recipient site demonstrated paresthesia at day 21 where the donor site resulted with an uneventful healing. At day 10, 5 (33%) patients demonstrated bleeding at their donor regions and resulted with a complete cessation of bleeding at day 21. Pain symptom was found in 8 (53.3%) recipient sites where 3 (20%) donor regions presented pain symptom at day 10. Graft shrinkage in the vertical dimension seems to affect the clinical outcomes of the FGG procedure. However, the influence of horizontal graft shrinkage was minimal.
Article
Healing of skin wounds involves inflammatory cells, keratinocytes, fibroblasts, inflammatory cytokines, angiogenesis, and growth factors. The kinetics of both the histological changes and cytokine expression during wound healing were studied in preparations of meshed Graftskin (Apligraf®), a bilayered cultured human skin construct. Within 12 hours of meshing, epiboly was observed at the cut edge of the tissue, and between 24 and 144 hours, tissue remodeling was complete. Inflammatory cytokines were increased soon after injury. Interleukin-1 alpha (IL-1α) was released immediately after Graftskin meshing, followed by an increase in IL-6 mRNA expression and protein synthesis. Tumor Necrosis Factor Alpha (TNFα) and IL-8 increased within the first four hours, and leveled off between 12 and 24 hours. Gene expression and protein production of growth factors associated with tissue remodeling, such as vascular endothelial growth factor (VEGF), endothelial cell growth factor (ECGF), and transforming growth factor (TGF-β1) were decreased in the first 24 hours of injury, but increased thereafter. The kinetics of cytokine production seem to correlate with the kinetics of wound healing. Interestingly, the level of platelet-derived endothelial cell growth factor (PD-ECGF), which has thymidine phosphorylase activity and is present in keratinocytes and skin extract, was depressed at the epiboly but not at the adjacent area. Taken together, the data suggest that Graftskin is a useful model system to investigate the process of wound healing and demonstrates the living cells in Graftskin are capable of responding to external stimuli.
Article
The present clinical trial was carried out in order to analyze whether a zone of keratinized and attached gingiva may regenerate following surgical excision of the gingiva. In addition the alterations occurring in the position of the “soft tissue margin” and the clinical attachment level were assessed. 6 patients, scheduled for periodontal surgery in the canine-premolar regions of both quadrants of the lower jaw, participated in the trial. A Baseline examination performed prior to surgery comprised assessments at the buccal surface of the teeth of dental plaque, gingivitis, probing depth, clinical attachment level, position of the “soil tissue margin” and width of the zones of keratinized and attached gingiva. The entire zone of keratinized and attached gingiva was removed surgically using either a “gingivectomy” or a “flap-excision” procedure. In the “gingivectomy” procedure the wounded area was left to heal by second intention, while in the “flap-excision” procedure the alveolar mucosa was repositioned in a coronal position to achieve complete coverage of the surgically exposed alveolar bone, During healing the patients' oral hygiene status was carefully supervised. All parameters included in the Baseline examination were assessed at reexaminations performed 1, 3, 6 and 9 months following surgery.
Article
Background. Tissue-engineered products are usually composed of living cells and their supporting matrices that have been grown in vitro, using a combination of engineering and life sciences principles. Apligraf is a bilayered product composed of neonatal-derived dermal fibroblasts and keratinocytes, and Type I bovine collagen. Objective. To evaluate in a prospective, multicentered open study, the effects of tissue therapy with a tissue-engineered skin (Apligraf) with partial or full-thickness excisional wounds. Methods. One hundred and seven patients participated in this study. The tissue-engineered skin was applied once, immediately after excisional surgery, usually for skin cancer, and patients were followed for up to one year. Results. The safety results were impressive, with no clinical or laboratory evidence of rejection. Clinically, graft persistence was good to excellent in 77 of 105 (73.3%) of patients at one week, falling to 56.6% and 53.6% at two weeks and one month respectively. Conclusion. To date, this is the largest experience with a tissue-engineered skin product in acute wounds, and this study suggests that tissue therapy may be safe and useful.
Article
The potential of Apligraf® (Graftskin) (Organogenesis Inc., Canton, MA), to improve cosmetic and functional outcomes when applied over meshed split thickness autografts was evaluated in a multicenter, randomized within patient controlled clinical trial. Experimental treatment sites had Apligraf® placed over meshed autograft while control sites were treated with meshed autograft covered with meshed allograft, or meshed autograft not covered by a biologic dressing. Forty patients were entered into this study of which 38 were evaluable. There was no difference in the percent take of autograft in the presence or absence of Apligraf® or in the median number of days to greater than 75% take of autograft. At the completion of the study 22 (58%) of the Apligraf® sites were rated superior to the control sites by the investigators, 10 (26%) were rated equivalent to the control and six (16%) were rated worse than control (p=0.0037). Pigmentation, in the Apligraf® group was significantly better than control and by month 24, 17 (45%) Apligraf® sites had normal pigmentation compared with five (13%) control sites (p=0.0005). Similarly by month 24, 18 (47%) patients had normal vascularity at the Apligraf® site compared with six (16%) patients at the control site. Improvements in pliability were observed with Apligraf® over control treatment within the first week of treatment. At month 24, 23 (61%) patients had normal height at the Apligraf® site compared to 14 (37%) with normal height at the control site (p=0.0117). Vancouver burn scar scores were shown to be statistically better at Apligraf® sites compared to control at all time points from week 1 to month 24. These results indicate that Apligraf® is a suitable and clinically effective treatment for burn wounds when applied over meshed autografts. Furthermore, cosmetic and functional advantages with Apligraf® were demonstrated when applied over meshed autograft compared to the current standard treatments of meshed autografts.
Article
To test the safety, efficacy, and immunological impact of a cultured allogeneic human skin equivalent (HSE) in the treatment of venous ulcers. Prospective, randomized study. Multicenter study in the outpatient setting. Each patient with a venous ulcer received either compression therapy alone or compression therapy and treatment with HSE. The patients were evaluated for HSE safety, complete (100%) ulcer healing, time to wound closure, wound recurrence, and immune response to the HSE. The study was completed as planned in 293 randomized patients. Treatment with HSE was more effective than compression therapy in the percentage of patients healed by 6 months (63% vs 49%; P=.02, Fisher exact test, 2-tailed) and the median time to complete wound closure (61 days vs 181 days; P=.003, log-rank test). Treatment with HSE was superior to compression therapy in healing larger (> 1000 mm2; P=.02) and deeper ulcers (P=.003) and ulcers of more than 6 months' duration (P=.001). Occurrence of adverse events was similar in both groups. No symptoms or signs of rejection occurred in response to treatment with HSE, and no HSE-specific immune responses were detected in vitro to bovine collagen or to alloantigens expressed on keratinocytes or fibroblasts. Treatment with HSE healed venous ulcers more rapidly and in more patients than compression therapy alone. There was no clinical or laboratory evidence of rejection or sensitization in response to HSE application. These data suggest that HSE represents a significant advance in the treatment of venous ulcers, particularly those that are difficult to heal.
Article
The present study was undertaken to analyze the role of attached gingiva for the maintenance of periodontal health in sites with normal and reduced height of the supporting apparatus. Furthermore, the effect of excision and grafting of gingiva on some parameters describing dimensions and location of the periodontal tissues was evaluated. 7 beagle dogs were used. A baseline examination comprised assessments of dental plaque, gingival conditions, attachment level, position of the gingival margin and width of the keratinized and the attached gingiva. In the right side of the jaws (experimental side) a 6month period of periodontal tissue breakdown was followed by surgical excision of the entire zone of the gingiva. After another 4-month period of healing with daily plaque control, a gingival graft was inserted in one quadrant of the experimental side to regain a zone of attached gingiva while the other quadrant of the experimental side was left ungrafted. In the left side of the jaws (control side), the teeth were subjected to daily meticulous plaque control during the entire study. In one of the control quadrants the entire zone of the keratinized and attached gingiva was excised at a time point corresponding to the grafing procedure in the experimental side, while the gingiva in the remaining control jaw quadrant was left unoperated. Clinical examinations of all control and experimental tooth units were repeated at certain time intervals during the course of the study. The final examination was carried out 4 months after grafting.
Article
The aim of this study was to test a new collagen matrix (CM) aimed to increase keratinized gingiva/mucosa when compared with the free connective tissue graft (CTG). This randomized longitudinal parallel controlled clinical trial studied 20 patients with at least one location with minimal keratinized tissue (<or=1 mm). Main Outcome Measure: The 6-month width of keratinized tissue. As secondary outcomes, the aesthetic outlook, the maintenance of periodontal health and the patient morbidity were assessed pre-operatively at 1, 3 and 6 months. At 6 months, the CTG attained a mean width of keratinized tissue of 2.6 (0.9) mm, while the CM was 2.5 (0.9) mm, these differences being insignificant. In both groups, there was a marked contraction (60% and 67%, respectively) although the periodontal parameters were not affected. The CM group had a significantly lower patient morbidity (pain and medication intake) as well as reduced surgery time. These results prove that this new CM was as effective and predictable as the CTG for attaining a band of keratinized tissue, but its use was associated with a significantly lower patient morbidity.
Article
The aim of this clinical study was to evaluate the treatment of gingival recession, associated with non-carious cervical lesions by a connective tissue graft (CTG) alone, or in combination with a resin-modified glass ionomer restoration (CTG+R). Forty patients presenting Miller Class I buccal gingival recessions, associated with non-carious cervical lesions, were selected. The defects were randomly assigned to receive either CTG or CTG+R. Bleeding on probing (BOP), probing depth (PD), relative gingival recession (RGR), clinical attachment level (CAL) and cervical lesion height (CLH) coverage were measured at baseline and 45 days, and 2, 3 and 6 months after treatment. Both groups showed statistically significant gains in CAL and soft tissue coverage. The differences between groups were not statistically significant in BOP, PD, RGR and CAL, after 6 months. The percentages of CLH covered were 74.88 +/- 8.66% for CTG and 70.76 +/- 9.81% for CTG+R (p>0.05). The estimated root coverage was 91.91 +/- 17.76% for CTG and 88.64 +/- 11.9% for CTG+R (p>0.05). Within the limits of the present study, it can be concluded that both procedures provide comparable soft tissue coverage. The presence of the glass ionomer restoration may not prevent the root coverage achieved by CTG.
Article
This study evaluated the safety and effectiveness of a tissue-engineered skin product composed of viable neonatal keratinocytes and fibroblasts and compared it to a free gingival graft (FGG) in a procedure to enhance keratinized tissue (KT) and wound healing around teeth that do not require root coverage. Twenty-five subjects were enrolled who had at least two non-adjacent teeth in contralateral quadrants exhibiting an insufficient zone of attached gingiva requiring soft tissue grafting where root coverage was not desired. One tooth was randomized to receive an FGG, and the other was randomized to receive bilayered cell therapy (BCT). The amount of KT was measured at baseline and 3 and 6 months, and the texture and color of the grafted tissue were compared to the surrounding tissue at months 1, 3, and 6. A questionnaire was used to determine subject preference at 6 months. Biopsies and persistence studies were performed on a subset of the subjects. The FGG generated statistically significantly (P <0.001) more KT than the test device (BCT) (4.5 +/- 0.80 mm versus 2.4 +/- 1.02 mm); no significant difference in recession or clinical attachment level was detected between treatment groups (P = 0.212 and P = 0.448, respectively); and no significant differences were detected at any time point for bleeding on probing (BOP), resistance to muscle pull, or inflammation. The BCT group had significantly better color and texture match with surrounding tissue (P <0.001), and subject preference was significantly greater for the BCT group (P = 0.041). No device-related adverse events or safety issues occurred during the course of the study. The tissue-engineered graft BCT was safe and capable of generating de novo KT without the morbidity and potential clinical difficulties associated with donor-site surgery. The amount of KT generated with FGG was greater than generated with BCT; however, 24 of 25 test sites demonstrated an increase in KT at 6 months, with more than three-quarters of the sites yielding > or =2 mm bands of KT.
Article
The present clinical trial was carried out in order to analyze whether a zone of keratinized and attached gingiva may regenerate following surgical excision of the gingiva. In addition the alterations occurring in the position of the "soft tissue margin" and the clinical attachment level were assessed. 6 patients, scheduled for periodontal surgery in the canine-premolar regions of both quadrants of the lower jaw, participated in the trial. A Baseline examination performed prior to surgery comprised assessments at the buccal surface of the teeth of dental plaque, gingivitis, probing depth, clinical attachment level, position of the "soft tissue margin" and width of the zones of keratinized and attached gingiva. The entire zone of keratinized and attached gingiva was removed surgically using either a "gingivectomy" or a "flap-excision" procedure. In the "gingivectomy" procedure the wounded area was left to heal by second intention, while in the "flap-excision" procedure the alveolar mucosa was repositioned in a coronal position to achieve complete coverage of the surgically exposed alveolar bone. During healing the patients' oral hygiene status was carefully supervised. All parameters included in the Baseline examination were assessed at reexaminations performed 1, 3, 6 and 9 months following surgery. Already 1 month after surgery all "gingivectomy" units and 9 out of the 14 "flap-excision" units demonstrated presence of a zone of keratinized gingiva. At the final examination (9 months following surgery) all surgically treated buccal areas had regained a zone of keratinized gingiva. However, a zone of attached gingiva reformed less frequently. The examination performed 3 months after surgery revealed that the "soft tissue margin" and the clinical attachment level had become displaced in apical direction, 0.9 and 0.4 mm, respectively. Between the 3-month and the 9-month examinations, however, no further alterations were observed and the gingival units were healthy, independent of the presence or absence of attached gingiva or the width of the zone of keratinized gingiva.
Article
To compare the behavior of a tissue-engineered living skin equivalent (LSE) with an autograft in acute donor site wounds. Paired-comparison, randomized control trial. A university dermatology service. Three donor sites were created on the anterior thigh of each of 20 patients requiring split-thickness skin grafts. For each patient, the donor sites were randomly assigned to be treated with meshed LSE, meshed autograft, or a polyurethane film (PUF) occlusive dressing. Blood and biopsy samples were taken for immunologic and histological studies. Toxic effects or clinically apparent rejection, humoral and cellular immune responses, clinical take, healing time, pain, and 1-month histological appearance. There was no toxic effect or clinically apparent rejection of LSE. Results of humoral and cellular studies were unchanged from baseline. The average time to healing for LSE with clinical take was 7.3 days (SD, +/- 0.8 days); for autograft, 7.6 days (SD, +/- 1.1 days); and for PUF, 9.5 days (SD, +/- 1.8 days). The difference between LSE or autograft and PUF was statistically significant at the .001 level. Pain was experienced by 1 patient, no patients, and 10 patients at the LSE, autograft, and PUF sites, respectively. Histologically, LSE had the thickest epidermis (P = .02), PUF had the greatest degree of fibrosis (P = .02), and autograft had the least degree of increased inflammation (P = .004) and vascularity (P = .01). In acute donor site wounds, LSE appeared to clinically take and to be a safe and usable form of tissue therapy.
Article
The potential of Apligraf(R) (Graftskin) (Organogenesis Inc., Canton, MA), to improve cosmetic and functional outcomes when applied over meshed split thickness autografts was evaluated in a multicenter, randomized within patient controlled clinical trial. Experimental treatment sites had Apligraf(R) placed over meshed autograft while control sites were treated with meshed autograft covered with meshed allograft, or meshed autograft not covered by a biologic dressing. Forty patients were entered into this study of which 38 were evaluable. There was no difference in the percent take of autograft in the presence or absence of Apligraf(R) or in the median number of days to greater than 75% take of autograft. At the completion of the study 22 (58%) of the Apligraf(R) sites were rated superior to the control sites by the investigators, 10 (26%) were rated equivalent to the control and six (16%) were rated worse than control (p=0. 0037). Pigmentation, in the Apligraf(R) group was significantly better than control and by month 24, 17 (45%) Apligraf(R) sites had normal pigmentation compared with five (13%) control sites (p=0. 0005). Similarly by month 24, 18 (47%) patients had normal vascularity at the Apligraf(R) site compared with six (16%) patients at the control site. Improvements in pliability were observed with Apligraf(R) over control treatment within the first week of treatment. At month 24, 23 (61%) patients had normal height at the Apligraf(R) site compared to 14 (37%) with normal height at the control site (p=0.0117). Vancouver burn scar scores were shown to be statistically better at Apligraf(R) sites compared to control at all time points from week 1 to month 24. These results indicate that Apligraf(R) is a suitable and clinically effective treatment for burn wounds when applied over meshed autografts. Furthermore, cosmetic and functional advantages with Apligraf(R) were demonstrated when applied over meshed autograft compared to the current standard treatments of meshed autografts.
Article
Human Skin Substitute (Apligraf, Organogenesis, Inc., Canton, MA) is a bi-layered tissue-engineered living biological dressing developed from neonatal foreskin. It consists of a bovine collagen matrix containing human fibroblasts with an overlying sheet of stratified human epithelium containing living human keratinocytes. Human Skin Substitute (HSS) appears to be immunologically inert, and has shown usefulness in the treatment of chronic and acute wounds. Primary objectives were to evaluate the safety and efficacy of HSS in the treatment of full-thickness wounds in a prospective case series. Secondary objectives were to determine the rate of complete wound reepithelialization, incidence of complete wound healing, pain at wound site, overall cosmetic outcome, and patient satisfaction. Fourteen patients were enrolled in the study, of which 12 were evaluable. HSS was applied in a blinded fashion to 6 of the patients immediately following Mohs or excisional surgery for skin cancer. The remaining 6 patients were allowed to heal by secondary intention. Both groups were evaluated at weekly appointments until complete reepithelialization occurred. During each evaluation, wound quality was assessed through the Vancouver Burn Scar Assessment Scale by the investigator and an independent blinded dermatologist. The investigator, blinded observer, and patient further evaluated the cosmetic outcome of the wound through the use of a Visual Analog Scale over a 6-month period. HSS patients and secondary intention patients were equivalent in comorbid factors such as pain, erythema, edema, exudate, infection, or hematoma between the groups. The incidence of complete wound healing at 6 months was 100% for both groups. Both groups also appeared to heal at similar rates, as defined by the complete reepithelialization of the wound. HSS patients ultimately resulted in more pliable and less vascular wounds as defined by the Vancouver Burn Scar Assessment Scale. Patient satisfaction with cosmetic outcome in both groups was positive at 6 months. HSS appears to be a safe, well-tolerated biological dressing with equivalent comorbid factors to secondary intention healing. HSS, however, seems to produce a more pliable and less vascular scar than those developed through healing by secondary intention. HSS also appears to produce more satisfactory cosmetic results when compared to secondary intention healing.
Article
Unlabelled: Bilayered living human skin equivalent (HSE) consists of cultured keratinocytes residing on the surface of a fibroblast-populated collagen lattice. Although HSE is FDA-approved for treatment of diabetic foot and venous stasis ulcers, its clinical efficacy remains limited, because the molecular mechanisms underlying its therapeutic effect are not fully understood. It is, therefore, often applied mistakenly as a skin graft. In this report, we delineate a mechanism of HSE biological effect and consequent optimal clinical use in accelerating closure of diabetic foot ulcers. Experimental: HSE was grafted onto nude mice and the release of various growth factors was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Clinical: HSE was grafted onto 11 consecutive patients with diabetes who had 13 non-ischemic foot ulcers and healing was measured as time to 100% closure (e.g., no drainage and 100% epithelialized). Experimental: HSE cellular components were determined to express 15 different growth factors/cytokine genes known to promote wound healing. Histological evidence from the nude mice showed that the collagen component of HSE underwent remodeling within the first seven days of grafting. Clinical: All diabetic foot ulcers healed in 31.8 12.4 days. Local release of a unique combination of 15 growth factors expressed by HSE keratinocyte and fibroblast components generates closure of diabetic foot ulcers. HSE should be applied with the same surgical conditions for a skin graft (i.e., no cellulitis, no drainage, and negligible bacteria). We hypothesize that bilayered HSE generates its effect by way of the local synthesis and release of multiple growth factors in specific combination and concentration, which improves the impaired reparative process of chronic wounds.
Article
The aim of this study was to evaluate the predictability of the free connective tissue graft in prosthetically treated patients needing gingival augmentation. The following outcome variables were studied 1) dimensional changes of free connective gingival grafts; 2) color blending with adjacent tissues; and 3) periodontal and marginal health status, when compared to a non-surgical control group. Two groups of patients without periodontitis were investigated. The test group (group A) consisted of 16 patients. The inclusion criteria for surgical correction were: 1) at least 1 site lacking (<1 mm) keratinized tissue and/or lacking vestibular depth; 2) insufficient plaque control; and 3) the selected site was scheduled to undergo or had already received a fixed prosthetic restoration. The control group (group B) included 14 patients with the same inclusion criteria, but declining to undergo surgery. Group A patients were treated with a free connective tissue graft to augment the keratinized tissue at the selected sites. The size of the graft was recorded at baseline (surgical intervention) and the width of keratinized tissue was measured at 1, 4, 26, and 52 weeks. Gingival inflammation and plaque accumulation were assessed at baseline and 52 weeks in both groups. Probing depth and clinical attachment levels were recorded at baseline and 26 and 52 weeks in both groups. Evaluation of the esthetic results was carried out at the end of the study. All patients in both groups received oral hygiene instructions and supragingival plaque and calculus removal before and at the end of the investigation. In group A, the results showed a mean amount of keratinized tissue of 5.81 +/- 1.42 mm at 26 weeks and 5.25 +/- 1.34 mm at 52 weeks. Mean shrinkage of the graft was 10.2% (P = 0.001) at 1 week, 28.4% (P = 0.0004) at 4 weeks, 37.2% (P = 0.0004) at 26 weeks, and 43.25% (P = 0.0004) at 52 weeks. All the dimensional changes were statistically significant, when compared to baseline. Evaluation of color blending with the surrounding gingiva demonstrated an "excellent result" at 52 weeks with an 87.5% agreement among the three masked examiners. In the test group, the periodontal indices improved or remained stable; in the control group, there was a minor improvement of the indices, with three patients showing a worse gingival inflammation score and two a worse plaque score. Although these results are not conclusive, mostly due to a lack of a large enough sample population, the statistically significant results shown in this investigation tend to support the use of gingival augmentation procedures in prosthetic patients with insufficient keratinized gingiva and/or shallow or absent vestibules, when they cannot demonstrate adequate plaque control.
Article
Apligraf consists of bovine collagen dermis seeded with allogeneic male fibroblasts and keratinocytes. It is been shown to promote healing, but the length of persistence and pathological features have not been characterized previously in acute wounds. Forty-eight deep dermal wounds were created and Apligraf, a split-skin graft (SSG), or a dressing was applied. Biopsies of wounds were taken for immunohistochemical analysis and polymerase chain reaction was performed to detect the Y chromosome from Apligraf cells in 14 female wounds. Male allogeneic DNA was detected in wounds for the first 4 weeks. All subsequent time points were negative apart from one biopsy at 6 weeks. The wounds took 4-9 weeks to heal, with the Apligraf exhibiting no features of engraftment. This was in contrast to the rapid healing seen in the SSG control group. Histology revealed a more intense cellular infiltrate, but less vascularization below Apligraf compared with controls. Evidence of an epidermal-mesenchymal interaction was observed. This is the first article to elucidate the survival of Apligraf allogeneic cells in acute wounds in immunocompetent human subjects for up to 6 weeks and demonstrates that in the management of acute surgical wounds, Apligraf has a role only as a temporary biological dressing.
Article
Attachment levels are excellent indicators of past destruction of the periodontal attachment apparatus and can be used to monitor the progression of periodontitis. They have been used in clinical trials to monitor the efficacy of a variety of therapeutic modalities that may either slow the progression of periodontal disease or allow for regeneration of lost attachment and supporting structures. Inherent difficulties in accurately assessing attachment levels include inflammation, which causes coronal displacement of the gingival margin without a concomitant migration of the dentogingival epithelium to a level apical to the cementoenamel junction, and recessions, in which an obvious loss of attachment has occurred, but there is no increase in probing depth. Attachment level measurements are more frequently used as clinical end-points in clinical trials than by private practitioners to determine the periodontal status of patients and to monitor patient responses to periodontal therapy. Clinical attachment level measurements have been used in clinical trials to evaluate a systemic host modulatory agent, demonstrating their utility as surrogate markers of efficacy.
Article
This was a prospective, randomized, controlled clinical trial assessing the safety and efficacy of a living bilayered skin construct (BSC; Organogenesis, Canton, MA) in treating full-thickness surgical excision wounds. We enrolled 31 patients needing excision of a non-melanoma skin cancer. The patients consisted of 18 females and 13 males, with an average age of 67 years (range: 44 to 84 years). Patients were randomized to either receive a single application of BSC or to heal by secondary intention. Endpoints to assess efficacy included time to complete wound closure, intensity and duration of post-operative pain, cosmetic appearance, patient satisfaction, and quality of the healed wound. Endpoints to assess safety included infection at the wound site and rejection of the BSC. Findings indicate that BSC is safe in the post-operative treatment of acute surgical wounds for removal of non-melanoma skin cancer. The data also suggest that BSC may facilitate management by decreasing post-operative pain. It is unclear whether or not BSC decreases healing time of acute wounds or results in a better cosmetic outcome.
Article
Apligraf is a bilayered tissue-engineered product consisting of a bovine collagen matrix with neonatal fibroblasts, overlaid by a stratified epithelium containing living keratinocytes. The United States Food and Drug Administration has approved its use for venous leg ulcers and neuropathic diabetic foot ulcers. Apligraf provides a dermal matrix and produces cytokines similar to the human skin. However, its mechanism of action and ultimate fate in host wounds are unclear. The aim of this study was to evaluate the persistence of Apligraf fibroblasts and keratinocytes in human acute partial-thickness wounds (split-thickness donor sites) treated with Apligraf. In an open-label, within-patient, three-centered, controlled pilot study, 10 patients were treated with Apligraf, Apligraf dermis only (without epidermis), and a polyurethane film for donor site wounds of the same size, depth, and anatomical location. Apligraf DNA persistence was the primary outcome measure. Basement membrane components, cosmetic outcome, time to wound healing, and safety parameters were secondary outcome measures. One week after the initial treatment, reverse transcription polymerase chain reaction analysis found that two Apligraf and two Apligraf dermis-only-treated sites had Apligraf DNA present. Four weeks posttreatment, only one Apligraf and one Apligraf dermis-only sites showed the presence of Apligraf DNA. There was no difference between the three treatment modalities in establishing basement membrane in donor site wounds. No differences in other secondary outcomes were found. Apligraf DNA persisted in a minority of patients at 4 weeks in acute partial-thickness wounds. Apligraf's success in speeding healing of acute wounds appears to be related to factors other than the persistence of donor DNA or effect on basement membrane restoration.
Article
An in vitro construct of human skin (living skin equivalent, LSE) has been engineered using serially passaged human epidermal keratinocytes and human dermal fibroblasts with a matrix of type I collagen. Cells are obtained from neonatal foreskin. LSE is cast, cultured, and shipped in a single culture insert. The size and shape of the insert determines the size and shape of the LSE. The dermal matrix consists of dermal fibroblasts within a condensed collagen lattice. The overlying epidermis is developed at the air-liquid interface to generate a protective cornified layer. Serum was not necessary for development of the epidermis. LSE for graft (Graftskin) has handling characteristics similar to split-thickness skin allowing it to be meshed, stapled, and sutured. LSE was cryopreserved using 65% glycerol an rapid freezing. Viability and in vivo performance on athymic mice were similar to fresh LSE. Cells derived from human eccrine gland were able to invade and form tubules rudimentary appendages may be possible.
Periodontal plastic and esthetic surgery Carranza's Clinical Periodontol-ogy
  • Takei Hh
  • Rr Azzi
  • Han Tj Newman Mg
  • Takei Hh
  • Pr Klokkevold
  • Carranza
Takei HH, Azzi RR, Han TJ. Periodontal plastic and esthetic surgery. In: Newman MG, Takei HH, Klokkevold PR, Carranza RA, eds. Carranza's Clinical Periodontol-ogy, 10th ed. St. Louis, MO: Saunders/Elsevier; 2006: 1005-1029.