William V Giannobile

• University of Michigan

Aim To assess tissue perfusion changes and wound healing biomarker levels after root coverage procedures with coronally advanced flap in combination with the cross‐linked xenogeneic collagen matrix (CCMX), loaded either with a placebo or recombinant human platelet‐derived growth factor‐BB (rhPDGF). Methods This study was designed as a secondary an...

Objective: Abaloparatide (ABL) is a synthetic parathyroid hormone-related protein analog developed as an anabolic drug to treat osteoporosis. ABL increases bone mineral density (BMD) of the long bones and spine; however, the influence of ABL on alveolar bone regeneration remains unknown. This study assessed the effects of systemic ABL administrati...

The cover image is based on the article Doppler ultrasonographic evaluation of tissue revascularization following connective tissue graft at implant sites by Lorenzo Tavelli etal., https://doi.org/10.1111/jcpe.13889 . image

Periodontal and peri-implant diseases are primarily biofilm-induced pathologies in susceptible hosts affecting the periodontium and dental implants. Differences in disease susceptibility, severity, and patterns of progression have been attributed to immune regulatory mechanisms such as epigenetics. DNA methylation is an essential epigenetic mechani...

Objective To identify gingival crevicular fluid (GCF)‐derived inflammatory markers of periodontitis progression and periodontal treatment impact. Methods Periodontally healthy (H; n = 112) and periodontitis (P; n = 302) patients were monitored bi‐monthly for 1 year without therapy. Periodontitis patients were re‐examined 6 months after non‐surgica...

At present, a lack of consensus exists regarding the clinical impact of osteoporosis on alveolar bone metabolism during implant osseointegration. While limited preclinical and clinical evidence demonstrates a negative influence of osteoporosis on dental extraction socket healing, no preclinical studies offer data on the results of implant placement...

Aim: To identify serum- and salivary-derived inflammatory biomarkers of periodontitis progression and determine their response to non-surgical treatment. Materials and methods: Periodontally healthy (H; n = 113) and periodontitis patients (P; n = 302) were monitored bi-monthly for 1 year without therapy. Periodontitis patients were re-examined 6...

Aim The aim of this study is to assess early wound healing expression of local angiogenic biomarkers following connective tissue graft (CTG) at dental implant sites. Methods Twenty‐eight subjects with single dental implants exhibiting a soft tissue dehiscence were included and randomly treated with CTG, either with coronally advanced flap (CAF) or...

Artificial intelligence (AI) is increasingly applied across all disciplines of medicine, including dentistry. Oral health research is experiencing a rapidly increasing use of machine learning (ML), the branch of AI that identifies inherent patterns in data similarly to how humans learn. In contemporary clinical dentistry, ML supports computer-aided...

Introduction: The aim of our study was to investigate the impact of diabetes-related factors on the dental disease outcomes of diabetes patients in Trincomalee, Sri Lanka. Materials and Methods: Dental data were collected from 80 type-2-diabetic individuals. A dental risk score was calculated based on the frequency of dental outcomes observed and c...

Aim To assess the Doppler ultrasonographic tissue perfusion at dental implant sites augmented with connective tissue graft (CTG) using coronally advanced flap (CAF) or tunnel technique (TUN). Materials and Methods Twenty‐eight patients presenting with isolated healthy peri‐implant soft‐tissue dehiscence (PSTD) were included in this randomized clin...

Aim To determine the effects of RVX‐208, a selective bromodomain and extra‐terminal domain (BET) inhibitor targeting bromodomain 2 (BD2), on periodontal inflammation and bone loss. Materials and Methods Macrophage‐like cells (RAW264.7) and human gingival epithelial cells were challenged by Porphyromonas gingivalis ( Pg ) with or without RVX‐208. I...

The human oral microbiome typically contains over 700 different microbial species. These interactions between the microorganisms within this community can shape the microenvironment throughout the human body, as these interactions are paramount to maintaining oral and overall systemic health. Recent advances in technology, such as next-generation s...

Background: to evaluate the long term outcomes of living cellular construct (LCC) compared to free gingival graft (FGG) for keratinized tissue width (KTW) augmentation in the natural dentition. Methods: Twenty-four subjects out of the original 29 enrolled participants were available at the 13-year follow-up. The primary endpoint was the number o...

Objectives: This randomized clinical trial assessed changes in protein biomarker levels and bacterial profiles after surgical reconstructive therapy of peri-implantitis, and investigated whether the adjunctive use of Er:YAG laser impacts protein biomarker and microbial outcomes. Materials and methods: Twenty-four patients received surgical recon...

Palatal‐tissue harvesting is a routinely performed procedure in periodontal and peri‐implant plastic surgery. Over the years, several surgical approaches have been attempted with the aim of obtaining autogenous soft‐tissue grafts while minimizing patient morbidity, which is considered the most common drawback of palatal harvesting. At the same time...

Importance Although many academic institutions have implemented infection control and prevention protocols, including regular asymptomatic self-testing, in response to the COVID-19 pandemic, the outcomes of mandatory surveillance testing programs at academic dental institutions that offer direct patient-facing clinical care has not yet been reporte...

Background With technological advancements in reconstructive periodontology, traditional protocols for the treatment of gingival recessions (GRs) can be challenged. This manuscript presents preliminary findings of a novel minimally‐invasive approach for the regenerative treatment of multiple adjacent GR defects. Methods Two healthy adults were tre...

A biologic is a therapeutic agent with biological activity that is administered to achieve an enhanced regenerative or reparative effect. The use of biologics has progressively become a core component of contemporary periodontal practice. However, some questions remain about their safety, indications, and effectiveness in specific clinical scenario...

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 an...

Periodontitis is a disease characterized by tooth‐associated microbial biofilms that drive chronic inflammation and destruction of periodontal‐supporting tissues. In some individuals, disease progression can lead to tooth loss. A similar condition can occur around dental implants in the form of peri‐implantitis. The immune response to bacterial cha...

Bmp‐Encoding Adenoviral Vector Tethered to Dental Implants Enhances Bone Regeneration In article number 2200531, Shogo Maekawa, Young‐Dan Cho, William Giannobile, and co‐workers demonstrate that immobilizing bone morphogenetic protein (BMP) genes onto the surfaces of dental implants by chemical vapor deposition technology enhances bone regeneration...

The objective of this pilot clinical study was to identify salivary biomarkers that are associated with periodontal disease and measures of diabetic autonomic dysfunction. Saliva samples from 32 participants were obtained from 3 groups: healthy (H), type 1 diabetes mellitus (DM), and type 1 diabetes mellitus with neuropathy (DMN). Based on the peri...

Aim: To evaluate the efficacy of recombinant human platelet-derived growth factor-BB (rhPDGF) combined with a cross-linked collagen matrix (CCM) for the treatment of multiple adjacent gingival recession type 1 defects (MAGRs) in combination with the coronally advanced flap (CAF). Materials and methods: Thirty patients were enrolled in this tripl...

For individuals who have experienced tooth loss, dental implants are an important treatment option for oral reconstruction. For these patients, alveolar bone augmentation and acceleration of osseointegration optimize implant stability. Traditional oral surgery often requires invasive procedures, which can result in prolonged treatment time and asso...

Aim: To assess the prognostic value of soft tissue phenotype modification following root coverage procedures for predicting the long-term (10-year) behaviour of the gingival margin. Materials and methods: Participants from six randomized clinical trials on root coverage procedures at the University of Michigan were re-invited for a longitudinal...

Aim: To assess the association between peri-implantitis and cardiovascular diseases (CVD). Methods: 128 patients with dental implants were recruited to evaluate the prevalence of peri-implantitis in patients with or without CVD (Cases, n = 82, Controls, n = 46, respectively). Diagnosis of peri-implantitis followed the 2017 World Workshop guideli...

Aim: To investigate the pro-inflammatory cytokine profiles in patients with or without cardiovascular disease (CVD) and with or without peri-implantitis. Methods: Serum, peri-implant crevicular fluid (PICF), and gingival crevicular fluid (GCF) were collected from patients with (n = 82) or without CVD (n = 46) at the most severe peri-implantitis...

Oral conditions are relatively common in patients with inflammatory bowel disease (IBD). However, the contribution of oral maladies to gut inflammation remains unexplored. Here, we investigated the impact of periodontitis on disease phenotypes of IBD patients. In all, 60 IBD patients (42 with ulcerative colitis [UC] and 18 with Crohn's disease [CD]...

Additive manufacturing (AM) is the automated production of three-dimensional (3D) structures through successive layer-by-layer deposition of materials directed by computer-aided-design (CAD) software. While current clinical procedures that aim to reconstruct hard and soft tissue defects resulting from periodontal disease, congenital or acquired pat...

Rationale: The endemic of peri-implantitis affects over 25% of dental implants. Current treatment depends on empirical patient and site-based stratifications and lacks a consistent risk grading system. Methods: We investigated a unique cohort of peri-implantitis patients undergoing regenerative therapy with comprehensive clinical, immune, and micro...

The cover image is based on the Original Article Ultrasonographic Tissue Perfusion Analysis at Implant and Palatal Donor Sites Following Soft Tissue Augmentation: A Clinical Pilot Study by Lorenzo Tavelli et al., https://doi.org/10.1111/jcpe.13424.

Aim To describe the application of power Doppler Ultrasonography (US) for evaluating blood flow at implant and palatal donor sites following soft tissue augmentation with the connective tissue graft (CTG). Materials and Methods Five patients exhibiting a per‐implant soft tissue dehiscence received treatment with a coronally advanced flap and corre...

Periodontal tissue engineering involves a multi-disciplinary approach towards the regeneration of periodontal ligament, cementum and alveolar bone surrounding teeth, whereas bone regeneration specifically applies to ridge reconstruction in preparation for future implant placement, sinus floor augmentation and regeneration of peri-implant osseous de...

Periodontitis is a complex multifactorial disease that can lead to destruction of tooth supporting tissues and subsequent tooth loss. The most recent global burden of disease studies highlight that severe periodontitis is one of the most prevalent chronic inflammatory conditions affecting humans. Periodontitis risk is attributed to genetics, host-m...

The new classification of periodontal diseases recognizes the key role of the interdental clinical attachment for defining the periodontal status and the extent of disease severity. Regenerating interdental clinical attachment not only improves the prognosis of the tooth, but it also lessens the severity of the disease condition. This manuscript pr...

Background: Periimplantitis is a challenging condition to manage and is frequently treated using non-surgical debridement. The local delivery of antimicrobial agents has demonstrated benefit in mild to moderate cases of periimplantitis. This study compared the safety and efficacy of Chlorhexidine gluconate 2.5 mg chip (CHX chips) as an adjunctive...

Destruction of the alveolar bone in the jaws can occur due to periodontitis, trauma or following tumor resection. Common reconstructive therapy can include the use of bone grafts with limited predictability and efficacy. Romosozumab, approved by the FDA in 2019, is a humanized sclerostin-neutralizing antibody (Scl-Ab) indicated in postmenopausal wo...

Aim: To develop and internally validate a nomogram built on a multivariate prediction model including parameters from the new classification of periodontal diseases, able to predict, at baseline, the occurrence of tooth loss due to periodontal reason (TLP). Materials and methods: A total of 315 individuals diagnosed with periodontal disease and...

Background: The peri-implant soft tissue phenotype (PSP) encompasses the keratinized mucosa width (KMW), mucosal thickness (MT) and supracrestal tissue height (STH). Numerous PSP approaches to augment soft tissue volume around endosseous dental implants have been investigated. To what extent PSP modification is beneficial for peri-implant health h...

At present, various tissue engineering strategies in the regenerative medicine have been developed for multiple tissue regeneration and integrative structure formations in musculoskeletal system. However, the regenerations of dental tissues or tooth-supportive structures are still challenging due to the micro-interfacial compartmentalization of mul...

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...

The precise mechanism by which oral infection contributes to the pathogenesis of extra-oral diseases remains unclear. Here, we report that periodontal inflammation exacerbates gut inflammation in vivo. Periodontitis leads to expansion of oral pathobionts, including Klebsiella and Enterobacter species, in the oral cavity. Amassed oral pathobionts ar...

After chronic low back pain, Temporomandibular Joint (TMJ) disorders are the second most common musculoskeletal condition affecting 5 to 12% of the population, with an annual health cost estimated at $4 billion. Chronic disability in TMJ osteoarthritis (OA) increases with aging, and the main goal is to diagnosis before morphological degeneration oc...

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...

Objectives: The mechanisms involved in the initiation and progression of peri-implantitis lesions are poorly understood. It was the aim to determine the content and activation status of macrophages present in human peri-implantitis lesions and compare the current findings with the macrophage polarization associated with periodontitis lesions. Mat...

Current regenerative strategies for alveolar bone and periodontal tissues are effective and well adopted. These are mainly based on the use of a combination of synthetic/natural scaffolds and bioactive agents, obviating the incorporation of cells. However, there are some inherent limitations associated with traditional techniques, and we hypothesiz...

This manuscript provides a state‐of‐the‐art review on the efficacy of biologics in root coverage procedures, including enamel matrix derivative, platelet‐derived growth factor, platelet concentrates, and fibroblast‐growth factor‐2. The mechanism of action and the rationale for using biologics in periodontal plastic surgery, as well as their anticip...

The present article focuses on the properties and indications of scaffold‐based extracellular matrix technologies as alternatives to autogenous soft tissue grafts for periodontal and peri‐implant plastic surgical reconstruction. The different processing methods for the creation of cell‐free constructs resulting in preservation of the extracellular...

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) augment...

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 the...

Aim To explore the M1/M2 status of macrophage polarization from healthy, gingivitis and periodontitis patient samples. Materials And Methods Gingival biopsies were collected from 42 individuals (14 gingivitis, 18 periodontitis, and 10 healthy samples) receiving periodontal therapy. Histomorphology analysis was performed with hematoxylin & eosin st...

Background and aims: To describe the biology of alveolar bone regeneration. Material and methods: Four comprehensive reviews were performed on (a) mesenchymal cells and differentiation factors leading to bone formation; (b) the critical interplay between bone resorbing and formative cells; (c) the role of osteoimmunology in the formation and mai...

The reconstruction of alveolar bone defects associated with teeth and dental implants remains a clinical challenge in the treatment of patients affected by disease or injury of the alveolus. The aim of this review was to provide an overview on advances made in the use of personalized scaffolding technologies coupled with biologics, cells and gene t...

The periodontium, consisting of gingiva, periodontal ligament, cementum, and alveolar bone, is a hierarchically organized tissue whose primary role is to provide physical and mechanical support to the teeth. Severe cases of periodontitis, an inflammatory condition initiated by an oral bacterial biofilm, can lead to significant destruction of soft a...

Background: Dental implants have been an important option for the replacement of missing teeth. A major clinical challenge is how best to accelerate bone regeneration and reduce the healing time for functional restoration after implant placement. Monoclonal antibody against sclerostin (Scl-Ab) has been shown to enhance alveolar bone formation and...

A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as “chronic” or “aggressive” are now grouped under a single category (“periodontitis”) and are further characterized based on a multi‐dimensional staging and grading system. Staging is largely dependent upon the severity of disease at pre...

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, o...

Objectives: The goal of Working Group 1 at the 2nd Consensus Meeting of the Osteology Foundation was to comprehensively assess the effects of soft tissue augmentation procedures on peri-implant health or disease. Materials and methods: A systematic review and meta-analysis on the effects of soft tissue augmentation procedures included a total of...

Objectives: One task of Working Group 1 at the 2nd Consensus Meeting of the Osteology Foundation was to comprehensively assess the effects of hard tissue augmentation procedures on peri-implant health or disease. Materials and methods: One systematic review and meta-analysis on the effects of hard tissue augmentation procedures included a total...

Aim: The goal of the present longitudinal cohort study was to examine patterns of periodontal disease progression at progressing sites and subjects defined based on linear mixed models (LMM) of clinical attachment loss (CAL) METHODS: 113 periodontally healthy and 302 periodontitis subjects had their CAL calculated bi-monthly for 12 months. LMMs we...

Specific orientations of regenerated ligaments are crucially required for mechanoresponsive properties and various biomechanical adaptations, which are the key interplay to support mineralized tissues. Although various 2D platforms or 3D printing systems can guide cellular activities or aligned organizations, it remains a challenge to develop ligam...

The field of tissue engineering and regenerative medicine (TE/RM) involves regeneration of tissues and organs using implantable biomaterials. The term epigenetics refers to changes in gene expression that are not encoded in the DNA sequence, leading to remodeling of the chromatin and activation or inactivation of gene expression. Recently, studies...

Objective: To evaluate the influence of periodontal therapy on DNA methylation in chronic periodontitis patients as compared to healthy individuals. Materials & methods: Twenty patients were enrolled into two groups: 1) 10 diagnosed as clinically healthy; and 2) 10 diagnosed with chronic periodontitis. Clinical measures were recorded and gingiva...

Approximately 40 years ago periodontists began systematically developing the evidence to treat predictably and prevent gingivitis and periodontitis. More recently, periodontists have been among a small group of skilled dental-implant surgeons leading that revolution in dentistry. Today, much of the mild/localized moderate periodontitis is not treat...

Objectives: We have previously applied linear mixed models (LMM) to longitudinal measurements of clinical attachment loss (CAL) to identify progressing periodontal sites. Using this methodology, we classi ed subjects as progressing or stable after 12 months of monitoring for changes in CAL. We then explored if baseline clinical parameters could be...

Purpose Facial crestal bone level and dimension determine function and esthetics of dentition and dental implants. We have previously demonstrated that ultrasound can identify bony and soft tissue structures in the oral cavity. The aim of this study is to evaluate the accuracy of using ultrasound to measure facial crestal bone level and thickness....

Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) promotes soft tissue and bone healing, and is FDA-approved for treatment of diabetic ulcers and periodontal defects. The short half-life of topical rhPDGF-BB protein application necessitates bolus, high-dose delivery. Gene therapy enables sustained local growth factor production. A nov...

Background and objectives: Within the same surgical procedure, a great variability on achievement of clinical outcomes exists and may be associated to different molecular factors related to tissue healing. The aim of the present study was to assess the distribution of clinical success separately in regenerative therapy (REG) and open flap debridem...

Table S1. Log odds ratio estimates (standard errors) from the ALR analysis with dichotomous outcome ∆CAL ≥1 mm versus ∆CAL <1 mm with change relative to baseline CAL. Table S2. Sites with the highest and the lowest mean PRESS statistics. Table S3. Sites with the highest and the lowest mean absolute PRESS residuals. Table S4. Quantiles mean PRESS...

Figure S1. (a) Line plot of clinical attachment loss (CAL) measurements for 30 sites with changes ≥2 mm in observed CAL measurements from baseline to 12 months from a single participant (subject X). (b) changes in CAL (ΔCAL) for the same 30 sites. (c) predicted CAL values from the linear mixed models for the same 30 sites over time. (d) changes in...

Purpose: Ultrasound imaging has potential to complement radiographic imaging modalities in implant and oral surgery given that it is non-ionizing and provides instantaneous images of anatomical structures. For application in oral and dental imaging, its qualities are dependent on its ability to accurately capture these complex structures. Therefor...

Aim: The goal of this study was to identify progressing periodontal sites by applying linear mixed models (LMM) to longitudinal measurements of clinical attachment loss (CAL). Methods: 93 periodontally healthy and 236 periodontitis subjects had their CAL measured bi-monthly for 12 months. The proportions of sites demonstrating increases in CAL f...

Molecules can be immobilized onto biomaterials by a chemical vapor deposition (CVD) coating strategy. Pentafluorophenolester groups react with amine side chains on antibodies, which can selectively immobilize adenoviral vectors for gene delivery of growth factors. These vectors can produce functional proteins within defined regions of biomaterials...

Aim: This exploratory randomized, controlled clinical trial sought to evaluate anti-inflammatory and -microbial effects of triclosan during experimental gingivitis as assessed by host response biomarkers and biofilm microbial pathogens. Materials and methods: Thirty participants were randomized to triclosan or control dentifrice groups who cease...

Scaffold design incorporating multiscale cues for clinically relevant, aligned tissue regeneration has potential to improve structural and functional integrity of multitissue interfaces. The objective of this preclinical study is to develop poly(ε-caprolactone) (PCL) scaffolds with mesoscale and microscale architectural cues specific to human ligam...

Diagnostics and prognostics in dentistry can be applied to stratify patients according to risk for individualized disease forecasting and, ultimately, targeting resources to maximize health outcomes. Traditional clinical measures of periodontal disease show a history of tissue destruction but are unable to determine biologic onset or initiation of...

To ensure a successful dental implant therapy, the presence of adequate vertical and horizontal alveolar bone is fundamental. However, an insufficient amount of alveolar ridge in both dimensions is often encountered in dental practice due to the consequences of oral diseases and tooth loss. Although postextraction socket preservation has been adopt...

The goal of periodontal therapy is to re-establish an adequate dento-alveolar environment supportive of tissue homeostasis. A regenerative outcome is the ultimate therapeutic goal. However, it is a general belief that lost alveolar bone, cementum and periodontal ligament (PDL) are not fully restored by conventional periodontal treatment. To promote...

Aims: To study the effect of the recombinant human bone morphogenetic protein 2 (rhBMP-2) on sinus volumetric and histometric changes after sinus floor augmentation compared to a conventional approach of non-biologic bone grafting materials. Materials and methods: An electronic search of 4 databases (January 1990-February 2015), including PubMed...

The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerativ...

Periodontitis is a chronic infectious disease driven by dysbiosis, an imbalance between commensal bacteria and the host organism. Periodontitis is a leading cause of tooth loss in adults and occurs in about 50% of the US population. In addition to the clinical challenges associated with treating periodontitis, the progression and chronic nature of...

Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. While the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response h...

The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of...

This chapter provides the clinician with foundational knowledge of bone development, composition, metabolism, and regeneration that serves as a primer for implant site development. It focuses on the three main functional cells that are ultimately responsible for the proper skeletal homeostasis. The bone formation activity is consistently coupled to...

The present invention relates to methods of measuring biomarkers to determine the probability of a periodontal and/or peri-implant disease. More specifically, the invention provides a panel of biomarkers that, when used in combination, can allow determination of the probability of a periodontal and/or peri-implant disease state with extremely high...

This satellite symposium was the fourth in a series for editors, publishers, reviewers and all those with an interest in scientific publishing. It was held on Wednesday 25(th) June 2014 at the IADR International Session in Cape Town, South Africa. The symposium attracted more than 180 attendees. This symposium placed an emphasis on how the quality...