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Efficacy and Safety of Hyaluronic Acid in the Management of Acute Wounds
Abstract
Hyaluronic acid (hyaluronan) is a key component of the extracellular matrix and is known to be involved in several mechanisms of the wound healing process. It has been shown to improve and accelerate the healing process of chronic wounds. This open-label study investigated whether application of hyaluronic acid could also improve the healing progression of acute wounds.
Forty-three patients with acute wounds, including trauma wounds, surgical sutures, burns, and dermabrasions, were included in the study. Hyaluronic acid (ialuset) was applied either as a cream or as a dressing, and the progression and quality of healing were evaluated at each application for a maximum of nine applications.
The mean surface area of the wounds decreased from 556 mm(2) at baseline to 169 mm(2) by the sixth evaluation, an average reduction of 70% in the surface area of the wounds. Complete healing occurred in 56% of cases by the sixth application. Little or no fibrin was observed in 91% of cases, and 84% of wounds showed little or no exudate. Both formulations of hyaluronic acid were well tolerated and were rated highly by nurses and patients for ease of use and treatment satisfaction.
Interpretation of the results of this open-label study is limited by the lack of a standard wound dressing as a comparator and by the varying types of wounds selected for inclusion. Nevertheless, the results of this study indicate that hyaluronic acid provides good healing of acute wounds and is well accepted by both patients and nurses.
... Sodium hyaluronate may enhance the mucosal repair and restoration of the mucosal protective layer. In facilitating wound healing [10], it is thought that sodium hyaluronate acts as a protective transport vehicle, taking peptide growth factors and other structural proteins to a site of action. HA has shown clinical effectiveness in several conditions where wound repair was the main therapeutic goal [10][11][12][13][14][15][16][17]. ...
... In facilitating wound healing [10], it is thought that sodium hyaluronate acts as a protective transport vehicle, taking peptide growth factors and other structural proteins to a site of action. HA has shown clinical effectiveness in several conditions where wound repair was the main therapeutic goal [10][11][12][13][14][15][16][17]. Based on these properties, it is expected that supplementation of sodium hyaluronate may provide a protective barrier to the lining of the colon affected by UC [18]. ...
... HA has been successfully used in medical conditions where wound repair is required, such as interstitial cystitis, perioral wrinkles, joint lesions, and nasal wounds [10][11][12][13][15][16][17]. In all these studies, patients treated with local administration of HA achieved wound repair and tissue restoration. ...
IBD98-M is a delayed-release formulation of mesalamine (mesalazine) and SH with a potential therapeutic role in ulcerative colitis (UC). A total of 51 patients with a modified Ulcerative Colitis Disease Activity Index (UCDAI) score of ≥4 and ≤10, and a modified UCDAI endoscopy subscore ≥1 were randomized for 6 weeks of double-blind treatment with IBD98 0.8 g/day or IBD 1.2 g/day or placebo. The efficacy and safety of IBD98-M in mild to moderate active UC were primarily evaluated. At week 6, 1 (5.9%), 2 (12.5%), and 2 (11.1%) patients receiving IBD98-M 0.8 g, IBD98-M 1.2 g, and placebo, respectively, (p > 0.999) achieved clinical remission. Higher clinical response was seen in IBD98-M 1.2 g (31.3%) versus placebo (16.7%) and endoscopic improvement in IBD98-M 0.8 g (29.4%) versus placebo (22.2%) was seen. Fecal calprotectin levels were reduced in IBD98-M groups versus placebo (p > 0.05). IBD98-M patients achieved significant improvement in physical health summary score component of the SF-36 (p = 0.01 and p = 0.03 respectively) compared to placebo. IBD98-M did not meet the primary end point but had higher clinical response (1.2 g/day) and endoscopic improvement (0.8 g/day) compared to placebo. The safety result shown that IBD98-M treatment was safe and well tolerated in this patient population. No new safety signals or unexpected safety findings were observed during the study. Further trials with different stratification and longer follow-up may be needed to evaluate the efficacy.
... Platelet gel which is a blood component obtained by mixing platelets, thrombin and/or calcium, exploits the effects of the cytokines contained in platelet α granules to stimulate the repair processes, its superiority comes from being of limited cost, easily prepared and of almost unlimited availability [10]. Hyaluronic acid which is a key component of the extracellular matrix that plays a key role in skin homeostasis due to its involvement in several mechanisms of the wound healing process [11]. ...
... On the contrary to our study, Bahar et al., [26] studied the effect of platelet rich plasma on wound ealing and found no significant difference in the time needed for healing. In Study by Voinchet et al., [11] on the effect of hyaluronic acid on acute wound healing on 43 patients, they reported that the 70% reduction of the wound surface area occurred within 10.8±1.5 days, which is similar to our finding that showed that the duration of complete healing ranged from 2-4 weeks with mean 3.4±0.7 weeks. Balbo et al., [10] who studied the use of platelet gel on fingertip injuries on 115 patients reported that the aesthetic results were excellent for 97% of the patients which is in agreement with our finding in which 7 out of 10 patients showed excellent outcome and the remaining 3 showed good aesthetic outcome. ...
... 13 Hyaluronic acid (HA) is considered to be an effective component in skin repair because of its multiple roles in the tissue regeneration process. 14 When combined with fibrin, HA has been proven to assist scar-less skin wound healing in rabbit model experiment. 15 It modulates inflammation, cellular migration, and tissue remodelling and controls matrix hydration, osmoregulation, and angiogenesis via specific HA receptors like CD 44, toll-like receptors contributing to the main phases of wound healing. ...
... 12,39,44 HA, as well as its degradation products that are generated in the wounds, is also capable of activating specific responses in all the cells involved in the process; in particular, fibroblast proliferation and new vessel formation have been extensively studied. 14,17,45 The results suggest that the biomimetic matrix deposition and its degradation products like GFs and ECM molecules could be responsible for enhanced fibroblast attachment and proliferation. ...
Regeneration of large sized acute and chronic wounds provoked by severe burns and diabetes is a major concern worldwide. Availability of immunologically compatible matrix with wide range of regenerative medical applications, more specifically, for non-healing chronic wounds is an unmet clinical need. Extrapolating the in vitro tissue engineering experiences for in vivo guided wound regeneration could be a meaningful approach. This study aimed to develop completely human, minimally immune-responsive scaffold comprising of acellular amniotic membrane (AM), fibrin (FIB) and hyaluronic acid (HA). The potential for in vivo guidance of skin regeneration was validated through in vitro dermal tissue assembly on the combination scaffold by growing human fibroblasts, differentiated from adipose derived mesenchymal stem cells (ADMSC). A new method was standardized for obtaining decellularized amnion (dAM) for assuring better performance. The biochemical stability of dAM upon plasma sterilization (pdAM) was demonstrated confirming its aptness for both in vitro & in vivo tissue engineering. The problem of poor handling characteristics was solved by combining the dried dAM with fibrin (FIB) derived from clinically used fibrin sealant kit. An additional constituent hyaluronic acid (HA), derived from human umbilical cord tissue, imparts the required water absorption and retention property for better cell migration and growth. Post-sterilization, the combination scaffold AMFIBHA demonstrated hemo-/cyto- compatible property confirming absence of detergent residuals. Upon long-term (20 d/40 d) culture of human fibroblasts, the suppleness of generated tissue was established by demonstrating regulated deposition of glycosaminoglycans, collagen and elastin using both qualitative and quantitative measurements. Regulated expressions of transforming growth factors (TGF)-β1 & TGF-β3, α-SMA, fibrillin-1, collagen subtypes and elastin suggest non- fibrotic fibroblast phenotype which could be an effect of microenvironment endowed by the AM, FIB and HA. In burn wound model experiments, immune response to cellular AM was prominent as compared to untreated control wounds and decellularized AM and AMFIBHA treated wounds ensuring biocompatibility. Wound regeneration with complete epithelialization, angiogenesis, development of rete pegs and other skin appendages was clearly visualized in 28 d after treating large sized (4 x 4 cm2) debrided full thickness burn wounds indicating guided wound regeneration potential of AMFIBHA.
... 17 Other treatments, such as Aloe vera, trolamine, sucralfate, and other hyaluronic acid formulations have not proved to be effective in treating radiodermatitis, and in some cases, they have even been counterproductive. [18][19][20][21][22][23][24][25][26][27] As radiodermatitis is a highly disabling condition and worsens the quality of life in cancer patients undergoing radiotherapy, and given that in the literature a particularly effective therapeutic approach has not been reported yet, it is essential to test new methods for the treatment of this bad complication. The application of products made with new formulations, which, as in this case report, offer promising results in terms of healing of the lesion and patient well-being, can lay the ground for more powerful studies, such as randomised controlled trials, to test their real effectiveness. ...
... 30 Other treatments, such as Aloe vera, trolamine, sucralfate, and other formulations of hyaluronic acid did not prove to be effective in the treatment of radiodermatitis, and some studies even found that they were counterproductive. [18][19][20][21][22][23][24][25][26][27] In the present study, treatment with HAG led to a rapid improvement of the lesion, and the patient perceived immediate benefit with the reduction of pain and discomfort caused by the crusts. ...
One of the principal side effects in patients that receive radiotherapy is radiodermatitis. Radiodermatitis can be highly invalidating for patients, causing pain, ulceration, swelling, and increased infection risk, with a negative effect on the quality of life, requiring dressings and medications. Therapeutic approaches reported so far in the literature have not proved to be effective in treating radiodermatitis. Therefore, new approaches are needed to deal with these side effects more effectively. The aim of the study was to evaluate the effectiveness of hyaluronic acid gel (HAG) (Jalosome soothing gel) for the treatment of a case of radiodermatitis. This is a case study of a patient affected by squamous cell carcinoma at the tongue base, who was treated with head and neck radiotherapy associated with the administration of cetuximab. About 1 month after this therapy was started the patient developed radiodermatitis, which did not regress with standard treatment. Therefore, HAG was applied once a day for about 20 days. The regression of radiodermatitis was measured using the Radiation Toxicity/Oncology Grading scale, pain relief was measured with a numerical scale, and patient satisfaction was done through a semi‐structured interview. The patient presented a dramatic reduction of skin toxicity, which had been resistant to all previous therapeutic approaches. Pain, which was severe at the beginning, gradually disappeared. The patient showed great satisfaction for the reduction of pain and the regression of the radiodermatitis. The effectiveness of HAG appears to be promising for the treatment of radiodermatitis.
... The low molar mass HA fragments, which accumulate due to degradation of high molar mass HA, induce fibroblast and keratinocyte migration and proliferation during proliferative and remodeling phases. Furthermore, the levels of HA synthesized by both fibroblasts and keratinocytes are elevated during re-epithelisation where epithelial cells migrate across the new tissue to form a barrier between the wound and the environment [21][22][23]. Accordingly, HA-containing scaffolds can be reputable candidates for wound dressing applications [23][24][25]. ...
... Furthermore, the levels of HA synthesized by both fibroblasts and keratinocytes are elevated during re-epithelisation where epithelial cells migrate across the new tissue to form a barrier between the wound and the environment [21][22][23]. Accordingly, HA-containing scaffolds can be reputable candidates for wound dressing applications [23][24][25]. ...
Structural and compositional similarity to the natural extracellular matrix (ECM) is a main characteristic of an ideal scaffold for tissue regeneration. In order to resemble the fibrous/gel structure of skin ECM, a multicomponent scaffold was fabricated using biopolymers with structural similarity to ECM and wound healing properties i.e., chitosan (CS), gelatin (Gel) and hyaluronic acid (HA). The CS-Gel and CS-HA nanofibers were simultaneously electrospun on the collector through dual-electrospinning technique. The presence of polymers, possible interactions, and formation of polyelectrolyte complex were proven by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and thermogravimetric analysis (TGA). The noncomplex component of CS-HA fibers formed a gel state when the scaffold was exposed to the aqueous media, while the CS-Gel fibers reserved their fibrous structure, resulting in formation of fibrous/gel structure. The CS-Gel/CS-HA scaffold showed significantly higher cell proliferation (109%) in the first 24 h comparing with CS (90%) and CS-Gel (96%) scaffolds. Additionally, the initial cell adhesion improved by incorporation of HA. The in-vivo wound healing results in rat elucidated more wound healing capability of the CS-Gel/CS-HA scaffold in which new tissue with most similarity to the normal skin was formed.
... Platelet gel which is a blood component obtained by mixing platelets, thrombin and/or calcium, exploits the effects of the cytokines contained in platelet α granules to stimulate the repair processes, its superiority comes from being of limited cost, easily prepared and of almost unlimited availability [10]. Hyaluronic acid which is a key component of the extracellular matrix that plays a key role in skin homeostasis due to its involvement in several mechanisms of the wound healing process [11]. ...
... On the contrary to our study, Bahar et al., [26] studied the effect of platelet rich plasma on wound ealing and found no significant difference in the time needed for healing. In Study by Voinchet et al., [11] on the effect of hyaluronic acid on acute wound healing on 43 patients, they reported that the 70% reduction of the wound surface area occurred within 10.8±1.5 days, which is similar to our finding that showed that the duration of complete healing ranged from 2-4 weeks with mean 3.4±0.7 weeks. Balbo et al., [10] who studied the use of platelet gel on fingertip injuries on 115 patients reported that the aesthetic results were excellent for 97% of the patients which is in agreement with our finding in which 7 out of 10 patients showed excellent outcome and the remaining 3 showed good aesthetic outcome. ...
Background: Fingertip injuries are the most common injuries that occur to the hand, accounting for 4.8 million Emergency Department visits per year. Fingertip injuries requires immediate intervention to avoid any complications or deformities. Several therapeutic modalities have been used for treatment; either surgical or conservative treatment and each of them has its own advantages and disadvantages. However, evidence is still lacking in the literature supporting either surgical or conservative lines of treatment. The purpose of the present study is to compare functional and aesthetic outcomes between surgical and conservative treatment of fingertip injuries.
... Táto činnosť uľahčuje migráciu, ktorá umožní monocytom, makrofágom a neutrofilom z periférie migrovať do rany smerom k centru a podporuje takto hojivý proces (6). O HA je tiež známe, že podporuje fagocytózu a angiogenézu (8). Roney a spol. ...
... HA aplikovaná vo forme krému výrazne urýhľovala hojenie rán, popálenín, či odrenín. Zaujímavým zistením bola malá tvorba fibrínových náletov a minimalizácia exsudátu (8). ...
... In spite of relatively high incidence of HF induced ocular burns, there is little information, regarding the optimal treatment modalities [4,5]. Efforts have been continued to find an ideal chemical agent, some of which like Alkanna tinctoria Tausch [28,29] and hyaluronic acid [2,30] play an important role for both corneal and dermal burns to promote healing. ...
Corneal burns were induced in 36 New Zealand white rabbits by instillationin both eyes of 0.05 mLof 2% hydrofluoric acid (HF) for 60 seconds.Following this, the eyes were irrigated with 500 mLisotonic saline (ISOT) andthen the rabbits were divided into 4 treatment groups (n = 9 rabbits each) inclu-ding: laminarin solution (LS), chitosan hydrogel (CHG), chitosan hydrogelcontaining laminarin (CHG+L) and ISOTas the control . For each treatmentgroup, one drop of each regimen was instilled 2 times a day and for periods of 2, 7 and 14 days respectively. Thus, 3 rabbits were used for each treatment per-iod in each treatment group. The eyes were clinically examined immediatelyafter the chemical burning and at days 1, 2, 7 and 14 of the follow up periods.The animals were euthanatized at the end of the follow-up periods and eyeswere processed for histopathological examination. Clinical and histopathologicalresults revealed that while LS or ISOTwas effective, CHG and CHG+Lwerenot effective in the treatment of HF corneal burns. LS had a better therapeuticeffect than ISOT. CHG and CHG+Ltreatment had no accelerating effect on thehealing of corneal erosion throughout the experimental procedures.
... Such polymers replace lost tissue and also facilitate wound healing. The use of 'smart' polymers either in the natural biological form or semisynthetic forms is reported to be able to mimic normal physiologic responses during wound healing 47,48 . This can be of major help in tissue regeneration, particularly for chronic wounds that are difficult to heal. ...
There are a wide variety of dressing techniques available for the management of both acute and chronic wounds. The primary objective in both the cases is to achieve a healed wound. An ideal dressing material should accelerate wound healing and reduce loss of necessary fluids from the wound, and also help minimize pain and infection. The present trend is to promote the concept of moist wound healing. This article emphasizes on the importance of assessment of the wound, the volume of drainage fluid, amount of damage, presence of infection and location of wound for optimal wound healing.
... Thus HA provides moisture and space-filling roles to the dermis. Coincidently, it also acts a reservoir of growth factors, apoenzymes and many other bioactives (Abatangelo, Martelli, & Vecchia, 1983;Voinchet, Vasseur, & Kern, 2006;P. Weigel, Frost, McGary, & LeBoeuf, 1987). ...
The integration of healing, cell biology, and skin tissue engineering research has been ongoing for nearly one century. In this chapter, we provide a bird’s eye view of skin anatomy and functions, wound healing processes, the challenges and solutions to wound healing. Many techniques and biomaterials have been examined for their potential utility as skin substitutes. Notwithstanding evidence that some strategies have been more successful than others, the ideal skin substitute does not exist. Existing skin substitutes suffer from poor mechanical properties, poor biocompatibility, poor immunocompatibility, poor integration, limited vascularization (poor survival), and fibrosis (scarring). However, the results from collaborative efforts between skin biologists, materials engineers and surgeons is providing transforming advances in this field and is delivering improvements for skin repair and regeneration. The combination of stem cells, vascularization, smart materials and customized bioprinting means that authentic skin substitutes that support skin regeneration are visible on the horizon.
... Hyaluronic acid has recently gained more attention for wound dressing formation because of its natural presence in the extracellular matrix and involvement in the inflammation and proliferation stages of wound healing [33]. It currently has clinical uses as wound dressings [33], skin substitutes [34], and joint lubricants [35]. Hyaluronan-based biomaterial (HYAFF-11) has improved mechanical integrity upon swelling by implementing an esterification crosslinking process [33]. ...
Wound dressings are critical for wound care because they provide a physical barrier between the injury site and outside environment, preventing further damage or infection. Wound dressings also manage and even encourage the wound healing process for proper recovery. Polysaccharide biopolymers are rapidly becoming popular as modern wound dressings materials because they are naturally derived, highly abundant, inexpensive, absorbent, non-toxic and non-immunogenic. Polysaccharide biopolymers have also been processed into biomimetic platforms that offer a bioactive component in wound dressings that aid the healing process. This review primarily focuses on the fabrication and biocompatibility assessment of polysaccharide materials. Specifically, fabrication platforms such as electrospun fibers and hydrogels, their fabrication considerations and popular polysaccharides such as chitosan, alginate, and hyaluronic acid among emerging options such as arabinoxylan are discussed. A survey of biocompatibility and bioactive molecule release studies, leveraging polysaccharide's naturally derived properties, is highlighted in the text, while challenges and future directions for wound dressing development using emerging fabrication techniques such as 3D bioprinting are outlined in the conclusion. This paper aims to encourage further investigation and open up new, disruptive avenues for polysaccharides in wound dressing material development.
... HA was shown to present with anti-inflammatory, anti-exudative, and antioxidative activity along with varied effects on angiogenesis [7,8]. It plays a significant role in all phases of the process of healing of wounds and injuries to the skin and mucous membranes [22,23] (Fig. 4.). ...
Introduction: Proton pump inhibitors (PPI) are an important breakthrough in the treatment of gastroesphageal reflux disease (GERD). However, in patients with laryngopharyngeal reflux (LPR), one of the extraoesophageal syndromes of this disease, the effectiveness of PPI therapy is partial or limited, and additional treatment is required to alleviate the symptoms. Currently, the important role of hyaluronic acid (HA) and chondroitin sulfate (CS) and their important role in the healing of mucosal damage, primarily the larynx, is emphasized. The aim of the study was to evaluate the results of treatment of patients with LPR by the oral combination preparation of hyaluronic acid and chondroitin sulfate (HA + CS) on a bioadhesive carrier. Material and methods: The study included 51 patients (18 men and 33 women) aged 25–75 years reporting symptoms of LPR, confirmed in the laryngovideoscope study. Patients were qualified for the study on the basis of reflux symptom index (RSI) above 13 points and the scale of reflux morphological symptoms of LPR in laryngofiberoscopic examination (reflux finding score; RFS) above 7 points. They were recommended to use the HA + CS combination for 14 days with subsequent evaluation. Results: Symptoms indicating a serious or severe problem (4 or 5 points on the RSI scale) before treatment are: grunting (48 patients; 90.19%), hoarseness (29 people; 56.86%) and coughing after eating/lying down (37 people; 72.50%). After treatment, the patients indicated that the above conditions limit their daily functioning to a moderate extent (p < 0.001). Symptoms such as the presence of mucus in the throat, a nagging cough, a feeling of obstruction in the throat, defined initially as moderate (3 points), after the supportive treatment decreased to a low level (1 point) (p < 0.001). The total RSI value after treatment was assessed as borderline for LPR diagnosis (median 13, range 12–15). The patient was not free of GERD symptoms, however, a significant reduction of discomfort was achieved in the whole study group. Morphological changes of the larynx before treatment most often included: redness/hyperemia, swelling of the vocal folds and hypertrophy of the posterior commissure. They were found in all patients. After treatment, the total RFS value below the LPR diagnosis limit (median 6, range 5–7) was observed, which compared to RFS (median 9, range 8–10) before treatment indicated a significant reduction of larynx changes in almost the entire study group (N = 50; 98.04%) (p < 0.001). Conclusions: A combined preparation of hyaluronic acid and chondroitin sulfate on a bioadhesive carrier, acting locally, significantly reduces the symptoms of laryngopharyngeal reflux, mainly in patients with: chronic cough, grunting and hoarseness. In addition, by covering the laryngeal mucosa with a protective layer, it allows better hydration and accelerates the healing process and regeneration of the mucosa, which in turn causes a reduction or withdrawal of morphological changes in the larynx.
... It is known that HA is involved in several mechanisms of the wound healing process. For example, it has been demonstrated that it improves and accelerates the wound healing of chronic wounds [21]. ...
The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is the emerging need for developing biopolymer-based composites capable of actively promote cellular proliferation and reconstitute the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan (CHI) and a mixture of chondroitin sulfate/hyaluronic acid (CS/HA), and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behaviour of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications.
... In a separate study, patients with second-degree burns were randomized to receive a topical cream containing either HA plus silver sulfadiazine (SSD) versus SSD alone (Costagliola & Agrosi, 2005). Those treated with the HA-SSD cream experienced shorter times to re-epithelialization. Several observational studies without control arms have shown satisfactory healing rates in wounds treated with HA products (Caravaggi, Grigoletto, & Scuderi, 2011;Gravante et al., 2007;Voinchet, Vasseur, & Kern, 2006), but it is impossible to determine from these studies whether the HA product truly improves healing. ...
Since the discovery of scarless fetal skin wound healing, research in the field has expanded significantly with the hopes of advancing the finding to adult human patients. There are several differences between fetal and adult skin that have been exploited to facilitate scarless healing in adults including growth factors, cytokines, and extracellular matrix substitutes. However, no one therapy, pathway, or cell subtype is sufficient to support scarless wound healing in adult skin. More recently, products that contain or mimic fetal and adult uninjured dermis were introduced to the wound healing market with promising clinical outcomes. Through our review of the major experimental targets of fetal wound healing, we hope to encourage research in areas that may have a significant clinical impact. Additionally, we will investigate therapies currently in clinical use and evaluate whether they represent a legitimate advance in regenerative medicine or a vulnerary agent. WIREs Dev Biol 2018, 7:e309. doi: 10.1002/wdev.309
This article is categorized under:
• Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration
• Plant Development > Cell Growth and Differentiation
• Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells
... During these phases the growth factors and cytokines released by the inflammatory cells induce fibroblast and keratinocyte migration and proliferation. In the second and third phases of healing endogenic HA binds with water, thereby contributing to a moist environment [20]. The levels of HA synthesized by both fibroblasts and keratinocytes are elevated during re-epithelisation where epithelial cells migrate across the new tissue to form a barrier between the wound and the environment [21]. ...
Two self-associating biopolymers, namely chitosan (Ch) and a high-molar-mass hyaluronan (HA), were used to prepare membranes with the aim to protect and to enhance the healing of injured skin. A mitochondrially-targeted antioxidant—MitoQ—was incorporated into the mixture of biopolymers prior to their self-association. These three-component membranes were evaluated in detail utilising surface roughness measurements, contact angle measurements, hemocompatibility, and thrombogenicity analyses. Furthermore, in vivo application of Ch/HA/MitoQ membranes was assessed on injured rabbit and rat skin utilizing histological methods. The results showed that the
prepared thrombogenic Ch/HA/MitoQ membranes had higher roughness, which allowed for greater surface area for tissue membrane interaction during the healing processes, and lower cytotoxicity levels than controls. MitoQ-loaded composite membranes displayed superior healing properties in these animal models compared to control membranes.
... 11 It also has been demonstrated to improve and accelerate the healing process of chronic wounds and the healing of acute wounds. 12 Other studies have shown that hyaluronic acid also improves the functioning of inflammatory mediators to reduce cell and skin degradation, and serves as an antioxidant that reduces the amount of reactive oxygen species. 13 Enhancing antioxidant and immune functions, zinc also maintains the integrity of biological membranes, plays a critical role in skin metabolism and repair, and has been shown to reduce inflammatory acne. ...
Background:
Superoxide dismutase (SOD) reduces the reactive oxygen species formation associated with oxidative stress. An imbalance between free radicals and antioxidants can lead to accelerated aging. GliSODin(®) Skin Nutrients Advanced Anti-Aging Formula (GAAF) is an SOD-containing dietary nutricosmetic formulated with other nutraceuticals that promote improvements in the structure and function of the skin, including hydration, elasticity, structural integrity, and photoaging caused by oxidative stress. Tazarotene cream 0.1% (TAZ) is a United States Food and Drug Administration-approved drug indicated for use in the mitigation of facial fine wrinkling, facial mottled hyper- and hypopigmentation, and benign facial lentigines when taken in conjunction with a comprehensive skin care and sun avoidance program.
Objective:
To determine if the antioxidant, anti-aging, hydrating and skin-rejuvenating properties of GAAF complement the retinoic actions of TAZ to improve the structure and function of facial skin.
Method:
A 90-day comparative study of ten subjects with facial photodamage; daily topical application of TAZ was used in combination with three capsules of GAAF (780 mg each) or placebo orally, with food, per the randomization allocation.
Results:
After 90 days of treatment, TAZ alone and in combination with GAAF improved fine wrinkles (↓1.2 versus 2.0), mottled hyperpigmentation (↓2.2 versus 2.8) and overall photodamage (↓1.0 versus 1.8), as well as patient-reported response to treatment (↓2.0 versus 1.6). At week 12, TAZ/GAAF combination treatment (Group A) versus TAZ treatment alone (Group C) was of significant clinical benefit, with respect to fine wrinkling (14.7%/41.7%), overall photodamage (15.6%/53.0%), skin moisture (19.1%/103.2%), skin elasticity (12.8%/87.7%), and response to treatment (8.8%/21.4%).
Conclusion:
The study suggests GAAF in combination with TAZ is safe and provides significant clinical benefit with relative improvement in facial fine wrinkling, overall photodamage, skin moisture and elasticity.
... Derivatives of hyaluronic acid (HA) are of particular importance within the field of dermal replacement products [2][3][4][5][6][7]. HA is the main degradation product in these substitutes and exerts many effects on wound healing, including maintenance of the homeostasis [8], enhancement of the angiogenesis [9] and organization of collagen deposition [10]. ...
This is an observational case series of 15 patients with full-thickness traumatic wound defects treated with a dermal substitute. There were 8 male and 7 female patients with a mean age of 36.6 years. Eight patients had trauma to the lower limbs and 7 were of the upper limbs, with the average lesion size 104.4 cm(2) (range 6-490 cm(2)). The time to complete healing had a mean average time of 26.8 days (range 16-60 days). All patients went on to successful repair with 6 patients requiring a second application of the substitute and 5 patients needing split thickness skin grafts. Infection was recorded in one patient.
... 12,13 It increases proliferation of keratinocytes and epithelial cellskey steps in the formation of new skinand facilitates movement of cells within the extracellular matrix, which also enhances dermal repair. 14,15 The Rhealba Oat plantlets extraction process is designed to release high levels of active principles such as flavonoids and saponins, without any protein to prevent patients from any sensitization effect. 16 Rhealba Oat plantlets extract have antiinflammatory properties with efficacy in pruritus and thus efficacy in inflammatory dermatosis [17][18][19] (atopic dermatitis, contact and irritant dermatitis, psoriasis). ...
Background:
The frequency of dermatological procedures is steadily increasing, accompanying a growing demand from patients. Chemical peels are a method of resurfacing in the treatment of various skin conditions. However, during the early healing process, patients may impose downtime on themselves. The erythema, pain and poor aesthetic appearance of the skin can lead to unwillingness to participate in social or professional activities.
Objectives:
The objective of this study was to evaluate the tolerance and efficacy of a repair cream based on Rhealba Oat plantlets extract and active healing compounds after a peeling procedure.
Methods:
Men and women, aged 18-65 years, with Fitzpatrick phototype I-IV, who had previously received a medium-depth chemical peel on the face (TCA 30%) entered with their consent a clinical study evaluating the new test product based on Rhealba Oat and active healing compounds. At the beginning of the study, the selected patients received a TCA 30% medium-depth peel. Afterwards, they were treated during 29 days with the repair cream and evaluated for the benefits to downtime and pain.
Results:
Significant reductions of pain (P < 0.0114) and erythema (P < 0.0001) were observed in the study. The downtime reduction with the tested cream was 92% - from 9 days after the previous peeling procedure to 0.74 days with application of the tested cream - a difference of 8.39 days.
Conclusion:
In consequence, the tested repair cream based on Rhealba Oat plantlets extract and active healing compounds brings clinical benefit to patients who undergo peeling procedures. By reducing pain and downtime, it allows patients to get back to their daily life activities a week earlier than with previous peels.
... 12,13 It increases proliferation of keratinocytes and epithelial cells -key steps in the formation of new skin -and facilitates movement of cells within the extracellular matrix, which also enhances dermal repair. 14,15 The Rhealba Oat plantlets extraction process is designed to release high levels of active principles such as flavonoids and saponins, without any protein to prevent patients from any sensitization effect. 16 Rhealba Oat plantlets extract have antiinflammatory properties with efficacy in pruritus and thus efficacy in inflammatory dermatosis [17][18][19] (atopic dermatitis, contact and irritant dermatitis, psoriasis). ...
BACKGROUND:
The frequency of dermatological procedures is steadily increasing, accompanying a growing demand from patients. Chemical peels are a method of resurfacing in the treatment of various skin conditions. However, during the early healing process, patients may impose downtime on themselves. The erythema, pain and poor aesthetic appearance of the skin can lead to unwillingness to participate in social or professional activities.
OBJECTIVES:
The objective of this study was to evaluate the tolerance and efficacy of a repair cream based on Rhealba Oat plantlets extract and active healing compounds after a peeling procedure.
METHODS:
Men and women, aged 18-65 years, with Fitzpatrick phototype I-IV, who had previously received a medium-depth chemical peel on the face (TCA 30%) entered with their consent a clinical study evaluating the new test product based on Rhealba Oat and active healing compounds. At the beginning of the study, the selected patients received a TCA 30% medium-depth peel. Afterwards, they were treated during 29 days with the repair cream and evaluated for the benefits to downtime and pain.
RESULTS:
Significant reductions of pain (P < 0.0114) and erythema (P < 0.0001) were observed in the study. The downtime reduction with the tested cream was 92% - from 9 days after the previous peeling procedure to 0.74 days with application of the tested cream - a difference of 8.39 days.
CONCLUSION:
In consequence, the tested repair cream based on Rhealba Oat plantlets extract and active healing compounds brings clinical benefit to patients who undergo peeling procedures. By reducing pain and downtime, it allows patients to get back to their daily life activities a week earlier than with previous peels.
... It is a glycoaminoglycan component of the extracellular matrix naturally occurring within the skin, cartilage and connective tissues. A recent clinical study has demonstrated that HA-based dressings are effective for managing acute wounds particularly in terms of its safety and efficacy [39]. Additionally, we have recently demonstrated that the commercially available HyStem HA hydrogel, modified to have nearly instantaneous in situ photocross-linking through thiol-ene chemistry, provides an ideal carrier for the delivery of stem cells or cellderived paracrine factors directly into full thickness excisional wounds [32]. ...
The early and effective treatment of wounds is vital to ensure proper wound closure and healing with appropriate functional and cosmetic outcomes. The use of human amnion membranes for wound care has been shown to be safe and effective. However, the difficulty in handling and placing thin sheets of membrane, and the high costs associated with the use of living cellularized tissue has limited the clinical application of amniotic membrane wound healing products. Here, we describe a novel amnion membrane-derived product, processed to result in a cell-free solution, while maintaining high concentrations of cell-derived cytokines and growth factors. The solubilized amnion membrane (SAM) combined with the carrier hyaluronic acid (HA) hydrogel (HA-SAM) is easy to produce, store, and apply to wounds. We demonstrated the efficacy of HA-SAM as a wound treatment using a full-thickness murine wound model. HA-SAM significantly accelerated wound closure through re-epithelialization and prevented wound contraction. HA-SAM-treated wounds had thicker regenerated skin, increased total number of blood vessels, and greater numbers of proliferating keratinocytes within the epidermis. Overall, this study confirms the efficacy of the amnion membrane as a wound treatment/dressing, and overcomes many of the limitations associated with using fresh, cryopreserved, or dehydrated tissue by providing a hydrogel delivery system for SAM. Stem Cells Translational Medicine 2017.
... The modality of the gel is based on human saliva, which relies on a similar mechanism to stimulate oral and skin primary wound closure, modulating the inflammatory response, especially in the early inflammation phase, which is involved in whole-wound healing. In addition, the properties of this gel, based on acid hyaluronic acid, also moderate the inflammatory response, which can contribute to the stabilization of the connective tissue matrix [24]. ...
Background:
Hyaluronic acid and amino acids play an important role in the wound healing process, stimulating the development of the connective tissue and the activity and proliferation of fibroblasts. The aim of the present controlled clinical study was to evaluate the clinical efficacy of a topical gel formula containing hyaluronic acid and amino acids in terms of wound closure rate, painkiller intake, and patients' reported pain and edema.
Methods:
This study included patients in need of a single tooth extraction. Patients were randomized into two groups with differing post-operative care regimens. Patients in the test group used the amino acid and hyaluronic acid-based gel, while the control group did not use any product. Each parameter was measured in both groups at different time points: immediately after surgery, and after 7, 14, 30, and 60 days.
Results:
A total of 40 patients (46.52 ± 9.84 years old) completed the observational period, and 40 extraction sockets were examined. After 7 days, the edema was significantly lower in the test group. The reported pain was lower in the test group without a significant difference, except for the first time point at 7 days. With the follow-up questionnaire, patients declared to have taken painkillers mainly during the first 7 days after surgery; however, the test group showed a lower need for painkillers than the control group.
Conclusion:
The post-operative and domiciliary use of an amino acid and hyaluronic acid-based gel for the management of soft tissue closure after tooth extraction is a valid coadjutant to reduce swelling, pain, and the need for painkillers. Additional studies are required to support the results of the present study.
... Hyaluronan has recently gained more attention for wound dressing formation due to its natural presence in the extracellular matrix (ECM) and involvement in the inflammation and proliferation stages of wound healing. HA is currently clinically used in wound dressings [2], skin substitutes [3], and joint lubricants [4]. Hyaluronan-based biomaterial (HYAFF-11), a commercialized biocompatible HA-matrix, has improved mechanical integrity upon swelling by implementing an esterification crosslinking process [2]. ...
Nano- and microfibers based on biopolymers are some of the most attractive issues of biotechnology due to their unique properties and effectiveness. Hyaluronan is well-known as a biodegradable, naturally-occurring polymer, which has great potential for being utilized in a fibrous form. The obtaining of fibers from hyaluronan presents a major challenge because of the hydrophilic character of the polymer and the high viscosity level of its solutions. Electrospinning, as the advanced and effective method of the fiber generation, is difficult. The nano- and microfibers from hyaluronan may be obtained by utilizing special techniques, including binary/ternary solvent systems and several polymers described as modifying (or carrying), such as polyethylene oxide (PEO) and polyvinyl alcohol (PVA). This paper reviews various methods for the synthesis of hyaluronan-based fibers, and also collects brief information on the properties and biological activity of hyaluronan and fibrous materials based on it.
... It plays an important role in wound healing through accumulation on the wound area, reinforcing angiogenesis and suppressing the growth of fibroblasts by absorbing free radicals, thereby reducing scar formation [4]. HA also contributes to maintaining the constancy of the epidermis by maintaining osmotic pressure; in addition, its many charged branches can reduce pain by retaining a large amount of moisture [5]. Previous studies of patients with recurrent apnea stomatitis found that the pain in the group with hyaluronic acid was significantly reduced [6,7]. ...
Background
Hyaluronic acid (HA) is well known to exert an anti-inflammatory effect during oral wound healing and is commonly applied after tooth extraction. However, no double-blind randomized controlled study comparing two hyaluronate mouthwash products has been conducted so far. The aim of this study was to comparatively analyze the efficacy of Mucobarrier® and Aloclair® in terms of clinical symptoms.
Results
A total of 112 patients were randomly assigned to assess the degree of discomfort, pain reduction, redness, burning sensation, and swelling between two groups on the day of surgery and 7 days later in a double blind test, with a total 56 Aloclair patients and 56 Mucobarrier patients. There was no statistically significant difference in the overall discomfort, degree of pain reduction, redness, burning sensation, and swelling between the Mucobarrier and Aloclair groups.
Conclusion
The local application of hyaluronic acid mouth wash after wisdom tooth extraction is beneficial in reducing overall discomfort and pain reduction, and the clinical utility of Mucobarrier® is no different from Aloclair®.
Trial registration
Institutional Review Board of Yonsei University College of Dentistry, 2-2018-0036. Registered 10 September 2018—prospectively registered, https://eirb.yuhs.ac/
... Hyaluronic acid (HA) is a natural polysaccharide constructed from two alternating units of N-acetyl-D-glucosamine and D-glucuronic acid [1,2]. It is an important component of the extracellular matrix and plays a role in wound healing and in controlling the release of growth factors [3][4][5]. Previous research has further shown that HA is very versatile in its use in medical treatment and tissue engineering because of its high biocompatibility, biodegradability, viscoelasticity, and non-toxic characteristics [5,6]. These properties make HA an ideal biomaterial for injectable hydrogels, wound patches, 3D bioprinting, tissue scaffolds, and drug delivery [7][8][9][10][11]. ...
Hyaluronic acid (HA) is a natural polysaccharide with great biocompatibility for a variety of biomedical applications, such as tissue scaffolds, dermal fillers, and drug-delivery carriers. Despite the medical impact of HA, its poor adhesiveness and short-term in vivo stability limit its therapeutic efficacy. To overcome these shortcomings, a versatile modification strategy for the HA backbone has been developed. This strategy involves tethering phenol moieties on HA to provide both robust adhesiveness and intermolecular cohesion and can be used for oxidative crosslinking of the polymeric chain. However, a lack of knowledge still exists regarding the interchangeable phenolic adhesion and cohesion depending on the type of oxidizing agent used. Here, we reveal the correlation between phenolic adhesion and cohesion upon gelation of two different HA–phenol conjugates, HA–tyramine and HA–catechol, depending on the oxidant. For covalent/non-covalent crosslinking of HA, oxidizing agents, horseradish peroxidase/hydrogen peroxide, chemical oxidants (e.g., base, sodium periodate), and metal ions, were utilized. As a result, HA–catechol showed stronger adhesion properties, whereas HA–tyramine showed higher cohesion properties. In addition, covalent bonds allowed better adhesion compared to that of non-covalent bonds. Our findings are promising for designing adhesive and mechanically robust biomaterials based on phenol chemistry.
... In fact, although it is well documented that during the wound healing process, the hyaluronic acid promotes cell proliferation, differentiation and motility, and moreover that a large availability of aminoacids is necessary because of increased metabolic activity [13,14], at present, few medical devices exists which contain all of them [11]. ...
Reduction of the wound healing time after surgical procedures along with good hemostasis, and the reduction of post-surgical edema, pain and infective complications are generally desirable to both clinicians and patients. Recently, a gel compound containing sodium hyaluronate and four synthetic aminoacids (glycine, leucine, proline, lysine) and marketed as Aminogam® (Errekappa Euroterapici, Italy), has been proposed as a medical device promoting faster wound healing after oral surgery procedures. To assess its achievable clinical benefits, we studied retrospectively 580 cases (290 study cases and 290 control cases) undergoing oral surgery and receiving Aminogam ® gel application. More precisely, cases were divided into 7 groups on the bases of the kind of surgery (teeth extraction, oral surgery in patients taking bisphosphonates, surgical treatment of jaw osteonecrosis related to bisphosphonates therapy, placement of endosseous implants, diode laser surgery of oral mucosa lesions with second intention healing without stitches, diode laser photocoagulation of slow flow vascular malformations and bone surgery). In all instances, Aminogam® gel was applied at least five times a day until the wound healed completely. We compared the elapsed time between surgery and complete healing with Aminogam® application compared to control cases receiving no other drug treatment. Our results confirmed that the overall time of healing is certainly reduced in cases receiving Aminogam® gel regardless of the kind of oral surgery.
... These dressings can be modulated into several different compositions and forms and they are capable of absorbing up to 20y times their weight [86]. Amid the several HA clinical uses, it is possible to observe wound dressings [87], joint lubricants [88], and skin substitutes [89]. One HA-based material, HYAFF-11, is a commercialized biocompatible HA matrix that has enhanced mechanical properties after an esterification cross-linking step [87], enabling a swelling up to 1000 times its weight for extremely exudative wounds while preserving mechanical integrity. ...
The wound healing process involves a basic feature of the human body for repairing damaged skin. Dressings have a significant role in the management of healing. Hence, it is known that natural polysaccharides have been demonstrated as promising candidates to promote wound healing owing to their impressive biological and mechanical properties. Polysaccharides dressing strategies based on nanotechnological approaches have enabled the improvement of wound care products given that biopolymers-based materials present suitable mechanical features that allow them to be straightforwardly shaped into membranes, hydrogels, and scaffolds. Moreover, blends of polysaccharides with other polymers offer numerous benefits for the design of skin-like materials including biomimetic characteristics and increased mechanical strength. Nevertheless, it is crucial to perform biocompatibility assays to achieve a safe and efficient new product that is in accordance with regulatory agencies. Finally, nanotechnology together with polysaccharides seems to be an outstanding approach for personalized regenerative medicine.
... Hyaluronic acid (HA) is a non-sulfated glycosaminoglycan and extracellular matrix component that acts as an immune regulator in physiological and pathological conditions (Noble et al., 2011). HA accumulates at sites of injury and inflammation where it is degraded by reactive oxygen species and hylauronidases, engaging in complex interactions with the wound environment to regulate cytokine secretion and influence immune cell migration (Voinchet et al., 2006). Methacrylation of HA enables light-activated crosslinking for easy formation of HA-based hydrogels (Ondeck and Engler, Chen et al. (2020) used methacrylated hyaluronic acid (Me-HA) hydrogels loaded with basic fibroblast growth factor (bFGF) as an injectable bioactive wound dressing (bFGF@Me-HA). ...
With few exceptions, humans are incapable of fully recovering from severe physical trauma. Due to these limitations, the field of regenerative medicine seeks to find clinically viable ways to repair permanently damaged tissue. There are two main approaches to regenerative medicine: promoting endogenous repair of the wound, or transplanting a material to replace the injured tissue. In recent years, these two methods have fused with the development of biomaterials that act as a scaffold and mobilize the body’s natural healing capabilities. This process involves not only promoting stem cell behavior, but by also inducing activity of the immune system. Through understanding the immune interactions with biomaterials, we can understand how the immune system participates in regeneration and wound healing. In this review, we will focus on biomaterials that promote endogenous tissue repair, with discussion on their interactions with the immune system.
... RECEBIDO Introdução O ácido hialurônico de baixo peso molecular (AH) é proposto como agente que atua nas três fases da reparação teciduall. A substância tem demonstrado eficácia na cicatrização de feridas por meio de estudos envolvendo animais 1 e seres humanos [2][3][4][5] . No mesmo sentido, tem sido empregada com base em seu efeito sobre fatores presentes nas três fases da cicatrização (inflamatória, proliferativa e remodeladora) 6 . ...
O ácido hialurônico (AH) atua nas fases inflamatória, proliferativa e remodeladora da cicatrização, enquanto fatores de crescimento de fibroblasto (FGF) agem na regeneração cutânea. Receptores ativados de FGF fosforilam resíduos de tirosina que mediam vias de sinalização intracelular, tais como PI3K-AKT, e resultados ex vivo sugerem sua relevância sobre a cicatrização, assim como das vias de sinalização ERK e PI3K. O objetivo deste trabalho foi avaliar mecanismos de ação do AH sobre a fase proliferativa da cicatrização, investigando sua capacidade de induzir a proliferação celular, de modular a expressão gênica dos FGF-7 e FGF-10 e atuar na sinalização das vias MEK/ERK e PI3K/AKT. Foram empregadas as técnicas de cultura celular, de azul de tripano, de brometo de [3-(4,5-dimetiltiazol-2yl)-2,5-difenil tetrazolium] (MTT) e de wound healing (WH). A expressão relativa dos genes FGF-7 e FGF-10 foi determinada pela reação em cadeia da polimerase quantitativa (qPCR) e a sinalização de MEK/ERK e PI3K/AKT ocorreu pela incorporação de seus anticorpos primários e secundários. Foram realizadas análises de 100.000 eventos em citômetro de fluxo. Após tratamento com AH, foi verificado aumento significativo na proliferação das células e nas fases S-G2-M do ciclo celular. O AH 0,2% promoveu redução significativa da área da lesão, com taxas de migração celular de 74% no modelo de WH. Houve aumento significativo na expressão de mRNA dos genes FGF-7 e FGF-10 (P<0.05). Foi observada a fosforilação de ERK1/2 e de MEK em comparação ao controle em ambas concentrações (0,1% e 0,2%). PI3K e AKT não mostraram fosforilação significativa após exposição ao AH. O AH induziu a proliferação e migração de fibroblastos através da ativação da via de sinalização ERK e demonstrou capacidade de aumentar a expressão relativa de mRNA dos genes FGF-7 e FGF-10. Tais achados são compatíveis com a aceleração do processo cicatricial por meio de interferências positivas em suas fases proliferativa e remodeladora. Técnicas de biologia celular e molecular foram de grande valia para o esclarecimento dos mecanismos de ação do AH, tornando possíveis a melhor compreensão de seus efeitos terapêuticos e a identificação de novas perspectivas de uso. (Revista Feridas • 2018; 06 (32) 1096-1102)
... O AH atua nas três fases da cicatrização (in amação, proliferação, remodelação) 7 e tem sido indicado no tratamento de lesões de difícil resolução, tais como úlceras diabéticas, queimaduras, úlceras pós-traumática, úlceras por pressão, úlceras de estase, úlceras venosas e úlceras pós-ebíticas [8][9][10][11] . Relatos também apontam para sua utilidade no tratamento de lesões decorrentes de erisipela bolhosa 12 . ...
A erisipela bolhosa é caracterizada por infecção bacteriana na camada superficial da pele e aparecimento de lesões cutâneas. Apesar do uso de antibióticos ser essencial nessa terapia, lesões decorrentes desta patologia são de difícil resolução, sendo necessário o correto manejo por parte da equipe de enfermagem. Nesse sentido, torna-se interessante o uso de adjuvantes capazes de acelerar o processo de reparação cutânea, como o creme à base de ácido hialurônico (AH). O objetivo deste trabalho foi relatar a experiência no tratamento de paciente portador de úlcera decorrente de erisipela bolhosa com o uso de creme de AH 0,2% e hidrogel. Trata-se de um relato de caso de paciente atendido pela equipe de enfermagem, em uma clínica de curativos de Aparecida de Goiânia-GO. Homem, 66 anos, portador de cardiopatia e erisipela bolhosa em membro inferior direito (MID), com ulceração na região da panturrilha. Em 05/01/16, deu entrada na clínica para tratamento desta lesão. Durante 8 meses, recebeu tratamento diário com limpeza com soro fisiológico 0,9% (SF 0,9%), desbridamento mecânico e aplicação tópica de produto com ação desbridante enzimática (colagenase) e, quando necessário, desbridamento instrumental. Em 29/08/16, optou-se por iniciar curativos com limpeza diária com SF 0,9% e aplicação de fina camada de creme à base de AH 0,2% (1x/dia), de segunda à quinta-feira. Nas sextas-feiras, era usado protocolo com limpeza com SF 0,9% e aplicação de hidrogel (1x/semana). A partir de 04/01/17, manteve-se curativo com SF 0,9%, desbridamento mecânico e hidrogel (1x/dia) de segunda à sexta-feira. Após a introdução do protocolo com AH e hidrogel no tratamento das lesões, foi possível observar evolução mais rápida e positiva no processo cicatricial, com aumento das aproximações das bordas e melhor alinhamento das mesmas. Paciente recebeu alta no dia 13/02/17, com a lesão totalmente cicatrizada. Verificou-se que a implementação de curativos envolvendo o uso de AH 0,2% associado ao hidrogel demonstrou ser uma opção terapêutica tópica eficaz na cicatrização deste tipo de ferida. Descritores: úlcera cutânea, ácido hialurônico, hidrogel, erisipela.(Revista Feridas 2018; 06 (28) 940-945)
[Bullous erysipelas is a bacterial skin infection involving the upper dermis and presents cutaneous wounds. Although the use of antibiotics is essential in this kind of therapy, lesions resulting from the pathology are difficult to solve, being necessary theirs correct management by the nursing team. In this case, it is interesting to use adjuvants able to accelerate the process of cutaneous repair, such as hyaluronic acid (HA) cream. The objective of this work was to report the experience in the treatment of a patient with ulcer due to bullous erysipelas with the use of 0.2% HA cream and hydrogel. This is a case report of a patient attended by nursing team, in a dressing clinic from Aparecida de Goiânia-GO. Male, 66 years old, with cardiopathy and bullous erysipelas in lower right limb (LRL), with ulceration in the calf region. On 05/01/16, he was admitted to the clinic for treatment of this lesion. During 8 months, the patient received daily treatment with normal saline solution (0.9% NaCl), mechanical debridement and topical application of enzymatic debriding agent (collagenase) and, as necessary, instrumental debridement. On 29/08/16, it was decided to start dressings with daily cleaning with 0.9% NaCl and application of thin layer of cream based on 0.2% HA (1x / day), from Monday to Thursday. On Fridays, the protocol used cleaning with 0.9% NaCl and application of hydrogel (1x / week). From 04/01/17, dressing was maintained with 0.9% NaCl, mechanical debridement and hydrogel (1x / day) from Monday to Friday. After the introduction of the protocol with AH and hydrogel in the treatment of the lesions, it was possible to observe a faster and more positive evolution in the healing process, with increased edge approximations and better alignment of them. Patient discharge occurred on 13/02/17, with a fully healed wound. The implementation of dressings involving the use of 0.2% HA associated with the hydrogel has been shown to be an effective topical therapy on the healing of this type of wound. Descriptors: skin ulcer, hyaluronic acid, hydrogel, erysipelas. (Revista Feridas 2018; 06 (28) 940-945) (Full paper in Portuguese)]
... Modern regenerative medicine, combustiology, and pharmacology require the design of effi cient materials that simultaneously exhibit wound-healing, anti-infl ammatory, and antibacterial activity, as well as the ability to release drugs in targeted and controlled fashion. These requirements are met by fi brous biopolymer composites 1-4 based on proteins, polysaccharides and their derivatives, such as collagen, 5 silk fibroin, 6 starch, 7 hyaluronic acid (HA), 8 chitin and chitosan, 9,10 alginic acid, 11 etc. Fibrous materials based on them can be used as wound dressing. ...
Hyaluronic acid (HA)-curcumin electrospun fibers exhibiting antimicrobial, anti-inflammatory, and anti-tumorigenic activity were fabricated. It is shown that a metachromatic complex between HA and curcumin is formed in a water-organic medium, thus stabilizing the electro-spinning process and improving the fiber characteristics. The polymer fibers prepared at a voltage of 26 kV have an average diameter of 0.296 μm (at a fiber diameter distribution from 0.146 to 0.630 μm). These HA-curcumin fibers can be widely used both in regenerative medicine and in the development of drug delivery systems.
... Research shows that natural hyaluronic acid does promote better scar formation 24,25 and has been implicated in assisting scarless healing. 26 I researched the value of hyaluronic acid immediately after needling starting 2007 and while I could not distinguish any special advantages in long-term results, the patients were much more comfortable in the immediate postneedling phase. ...
This is a brief history of the beginnings of skin needling (collagen induction therapy) and Part 1 covers the original clinical work which was then validated by research primarily by Matthias Aust and team at Hanover Medical School, Germany. Skin needling became the very first medical procedure that induces regeneration instead of scar formation because it employs transforming growth factor‐β3 (TGF‐β3) and interleukin‐10 (IL‐10). We essay into methods to optimise the effects of skin needling. First by the depth of penetration into the skin which will depend on the condition treated. Wrinkles stretch marks, and so on only require 1.0 mm whereas burns scars acne scars, and so on require deeper penetration, that is, approximately 3.0 mm. In Part 2, we need to consider the use of topicals both before and after skin needling. Vitamins A and C are scientifically proven to almost quadruple the effects of needling. Selected peptides seem to further enhance results. Hyaluronic acid is best induced naturally but may be used topically for comfort. Finally, we examine the rationale of the intervals between needling. The best clinical results seem to come from treatments at 4 to 10 days intervals to take advantage of raised titres of TGF‐β3 and IL‐10. Other modalities such as red and infrared LED, platelet‐rich plasma and mild peeling are gaining appeal to give better results. Skin needling is the safest and most effective method to treat photoaging, lax skin, stretch marks, acne scars, and burn scars.
To explore the efficiency and safety of hyaluronic acid for burn victims, we searched for all the relative references, selected the references according to the inclusion criterion, assessed them critically and conducted Metaanalysis. The experimental group and the control groups have statistically significant difference in the average time for wound healing. If we make subgroup analysis according to the origin, the outcomes of both foreign study and Chinese study have statistical significance. No statistically significant difference is revealed in the incidence of adverse reaction. In terms of the healing time for diverse burn wounds, statistically significant difference exists in the superficial seconddegree burn. There is no statistically significant difference in deep seconddegree burn, skingrafting sites and donor sites. It revealed that hyaluronic acid can accelerate the healing of burn on skin, especially for superficial seconddegree burn. And its adverse reaction by external use is negligible. © 2013 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University.
Skin is the largest organ of the human body. It is highly susceptible to injury. Typically, adult skin wounds heal via scar formation rather than regeneration. Thus, skin presents an excellent model to investigate mechanisms of scar formation to gain insight on regeneration. To date, there has been limited success in the development of therapeutics for scar-free regeneration through traditional approaches. Therefore, the development of a transdisciplinary approach to the investigation and development of therapeutics for scar-free regeneration is needed. The regenerative engineering approach involves the convergence of advanced materials science, stem cell science, physics, insights from developmental biology, and clinical translation. In this review, we describe some key aspects of scar-free skin regeneration from the perspectives of developmental biology. Then, we discuss multifaceted approaches such as the use of organism-derived tissues, cell-based strategies, and material-based strategies, towards scar-free skin regeneration. Regenerative engineering approaches using biomaterials combined with biological cues from physics and developmental biology hold significant potential for bringing new promising strategies to support scar-free skin regeneration. Lay Summary: Skin is one of the largest and most vital organs. Severe damage to mammalian skin leads to failed healing and scar formation. There has been limited therapeutic success in creating scar-free skin regeneration. We believe the solution to scar-free skin regeneration in humans may lie in adopting a transdisciplinary approach to solve the problem. In this review, we first discuss the influence of biological cues on regeneration from studies using regeneration competent animals and fetus mammals. Next, current regenerative engineering approaches such as the use of organism-derived tissues, cell-based strategies, and material-based strategies are discussed. Finally, we provide future perspectives on achieving scar-free skin regeneration.
Since decades, the field of wound healing has gained immense attention from the researchers worldwide. The ultimate goal is to develop effective techniques that can speed up the healing process and avoid scar formation to facilitate proper wound management. This has resulted in advances and discoveries in different biopolymeric nanosystems and their combinations as wound healing agents as alternatives for conventional wound dressings. This review primarily outlines wound healing cascade by human body’s natural defence mechanism and highlights the recent developments in wound healing agents. The aim of the review is to discuss the suitability of biopolymeric nanosystems based on chitin, chitosan, collagen, alginate, fucoidan, gelatin, silk fibroin and hyaluronic acid as potential wound healing agents to provide wound healing environment for enhanced healing rate.
Hyaluronic acid, a high-molecular-weight biopolymer, is of special interest as carrier material in drug delivery due to its biocompatibility, biodegradability, special viscoelastic properties, as well as its ability to create a dense network in which drugs might be incorporated. Hyaluronic acid has a broad applicability in various conditions such as in cosmetic products in terms of anti-wrinkle treatment and skin hydration, local drug delivery, intra-articular injection into arthritic joints and visco-supplementation in ophthalmology.
This chapter focuses on the use of hyaluronic acid-based formulations in cosmetics as well as for intra-/transdermal delivery of drugs. We elucidate the role of hyaluronic acid/fragments as a skin penetration enhancer and tried to highlight the properties of hyaluronic acid which make them unique in the field of drug delivery.
The integration of healing, cell biology, and skin tissue engineering research has been ongoing for almost 60 years. In this chapter, we provide an eagle's eye view of skin anatomy and functions, wound healing processes, and the challenges related to wound healing that tissue engineers face. Several biomaterials have been examined for their potential use in skin substitutes to replace/regenerate skin with normal structure and function. However, it is obvious that the ideal skin substitute does not exist. The problems and challenges in the skin substitutes currently available include low mechanical properties, lack of biocompatibility, minimal structural differentiation, limited vascularization (low take rate), and scar development. However, an articulation between skin tissue engineering and regenerative medicine may bring transforming advances in this field that may lead to the ability to restore skin structure and function. Through the combination of stem cell manipulation, angiogenesis control, advanced bioactive molecules, and smart biomaterials development, it may be possible to design an authentic skin substitute or an engineered composite that induces skin regeneration.
OBJECTIVE: To explore the effectiveness and safety of hyaluronic acid in preventing postoperative abdominopelvic adhesions. METHODS: Appropriate search strategy and inclusion and exclusion criteria were made. The Cochrane Library, EM-BASE, PubMed, ISI database, CBM, CNKI, VIP, and Wanfang database were searched for randomized controlled trials (RCTs) a-bout hyaluronic acid in preventing postoperative abdominopelvic adhesions. RCTs were selected and included according to the inclusion and exclusion criteria. Then quality assessment and meta-analysis were conducted on the included RCTs. RESULTS: Five high quality RCTs were included. Statistical difference was detected in the rate of postoperative abdominopelvic adhesions (P<0.00001). Both hyaluronic acid membrane (P<0.00001) and hyaluronic acid gel (P<0.00001) could reduce the extent of postoperative adhesions. Meanwhile, both hyaluronic acid membrane (P<0.00001) and hyaluronic acid gel(P<0.00001) could alleviate the severity of postoperative adhesions. The two groups had no statistical difference in total incidence of adverse reactions (P = 0.07). CONCLUSION: Hyaluronic acid can reduce the incidence of postoperative abdominopelvic adhesions and decrease the extent and severity of postoperative adhesions, with low incidence of adverse reactions. Patients can benefit form hyaluronic acid if it is applied to proper indications under standard operation.
Background: Endonasal endoscopic dacryocystorhinostomy (EES-DCR) has been evidenced with a quite satisfying outcome for chronic dacryocystitis. But whether the artificial lacrimal silicone intubation in this procedure can improve the operative effectiveness was still in controversy. Objective: The aim of this trial was to investigate the influence of artificial lacrimal silicone intubation in EES-DCR on the outcome of the treatment of chronic dacryocystitis. Methods: This is a prospective clinically randomized controlled trial. One hundred eighty patients with chronic dacryocystitis were randomly assigned to bicanalicular silicone intubation + EES-DCR group and only EES-DCR group. Conventional EES-DCR was performed for the patients in only EES-DCR group, and artificial lacrimal silicone tube was intubated after EES-DCR in bicanalicular silicone intubation group. The regular follow-up was curried out after surgery. The status of wound was examined under the nasal endoscope. The patency rate of ostium was recorded and compared between two groups. Written informed consent was obtained from each patient prior to surgery. Results: 23 cases (23 eyes) was excluded in this study because of the accordance of operation, and 157 cases finished this trial with 73 cases in bicanalicular silicone intubation group and 84 cases in conventional EES-DCR group. No evident differences were found in demography between two groups (P > 0. 05). The post-operation follow-up duration was from 12 to 18 months (mean 14.1 ± 1.1 months). The successful rate of lacrimal system reconstruction was 89.0% (65/73) in bicanalicular silicone intubation group and 92.9% (78/84) in conventional EES-DCR group. No significant statistical difference was found between two groups (χ 2 = 0.700, P = 0.403). From 7 to 14 days (mean 9.3 ± 1.7 d) after operation, the wound surface around the lacrimal ostia was covered by a perfectly epithelized mucosa in 62 cases of bicanalicular silicone intubation group and 70 cases of conventional EES-DCR group. Scar and/or granulation around the lacrimal ostia was found in 15.1% (11/73) patients in bicanalicular silicone intubation group and 9.5% (8/84) patients in conventional EES-DCR group, showing a statistical difference between two groups (χ 2 = 157.000, P = 0.000). Conclusion: Bicanalicular silicone intubation + EES-DCR could not improve the therapeutic outcome of EES-DCR. Moreover, bicanalicular silicone intubation, to some extent, stimulates scar formation and/or granulation around the lacrimal ostia after operation.
Background
In France, almost 40% of burn hospitalizations involve children between 0 and 15 years old. A care protocol with a dressing using hyaluronic acid (ialuset®, Laboratoires Genevrier, Antibes, France) was implemented by the Department of Pediatric Surgery of Besançon University Hospital for such burns in children.
Methods
The study was a retrospective observational study including children with second-degree burns covering less than 20% of the body surface, who, being less than 15 years old, were treated within 24 hours of the burning incident by Besançon University Hospital and received first-line treatment protocol using hyaluronic acid (HA) cream or gauze, between January 2016 and January 2019. The study endpoints were the proportion of epidermized burns after 3 weeks of treatment, time to healing, and tolerance to the tested product used.
Results
In total, 92 patients were screened at Besançon University Hospital and 74 were eligible, 135 burns were analyzed, and 792 dressings were applied. The average age of patients was 3.8 years old. Overall, 130 burns (96.3%) epidermized within a median time of 14 days [2; 45]. Among patients whose treatment failed, two were grafted. No adverse effects due to the application of hyaluronic acid-based gauze or cream were reported.
Conclusion
A care protocol using HA-based dressing is an effective and safe alternative in the treatment of second-degree burns of children.
3D-scaffolds composed of polyvinyl alcohol-hyaluronan (PVA/HA) nanofiber mats were fabricated by electrospinner. Spinning conditions of PVA/HA were optimized for obtaining uniform and smooth nanofibers (NFs). Resultant NFs were investigated by SEM, FT-IR and mechanical tensile. Chitosan was incorporated into NFs mats during spinning for reducing bleeding, microbial growth of wound bed, and enhancing viability/proliferation of cells in damaged tissues. Hydroxyapatite (HAP) after silanization using (3-aminopropyl)triethoxysilane (APTES) was also incorporated into scaffolds due to its similar chemical composition with mineral composition of bone, which stimulates interactions between bone tissue and biomaterial resulting in a prominent interface after implantation. NFs with different compositions were bio-evaluated in vitro using antimicrobial activity, hemolysis(%), cytotoxicity, and cell adhesion tests. Results revealed that, addition of HAP into PVA/HA mats improved significantly their mechanical/thermal stability and relatively hindered swelling index, compared to mats without HAP. However, addition of chitosan enhanced swelling index and antimicrobial activity of mats. All tested mats with different compositions showed high cell-viability, regardless incubation time or concentration of tested nanofibers. In-vitro cell adhesion results indicated that, WI38 cells adhered and proliferated adequately with nanofibers containing HAP. Such findings support the ability for using PVA/HA/CH/HAP NFs as biomaterials for bone tissue regeneration soon.
Since hyaluronate (HA) was firstly isolated from the vitreous of bovine eyes in 1934, HA has been widely investigated for various biomedical applications. As a naturally-occurring polysaccharide, HA has been used for joint lubrication and ocular treatment in its intact form due to the excellent biocompatibility, viscoelasticity, biodegradability, and hygroscopic properties. HA can be easily functionalized via the chemical modification of its carboxyl and hydroxyl groups. Recently, a variety of biological functions of HA have been explored and a number of customized applications have been investigated taking advantages of the interaction between HA and biological tissues. HA has been used for drug delivery to enhance the blood circulation time of drugs with target-specificity to HA receptors in the body. HA has been also used to prepare tissue engineering hydrogel scaffolds for the spatiotemporal control of encapsulated cells. In this review, we describe the key biological functions of HA in the body in terms of its structure, physical properties, biodistribution and interaction with HA receptors. After that, we describe unique advantages that allow HA to be applied in various biomedical fields. Finally, we report the conventional and newly emerging applications of HA and its derivatives under commercial development stages.
Utilization of underlying mechanisms of biological system is a primary pursue of biomimetics for a primary goal to treat on-going biological process. From tissue engineering perspective, one purpose of biomimetics is to create highly cellular or tissue-favored-environments for bio-defect repair. Marine creatures, such as mussel, have inspired bioengineer to design ideal cellular substrate, strong adhesives, and other bioengineering materials. Here we report a novel mussel shell-derived membrane for wound dressing. Mussel-shell were manufactured in-situ a highly flexible membrane with regularly porous pattern after the direct action of acid (A-shell) followed by base treatment (B-shell). From SEM elegantly patterned polygons with nano-wall (about 710 nm) were presented. Compared with A-shell, the B-shell has more clear and flexible structure. FTIR characterization of structure showed the deacetylation on B-shell. Cellular toxic study was conducted for an optimized processing parameters before in a wound healing model. B-shell significantly closed the wound at an early stage (day 10) followed by complete contraction at later stage (day 21). It was completely consistent with the higher level of α-SMA protein, which accelerates wound contraction in the wound sites. As key index of the integration between host and guest, higher blood vessel density was detected in both A-shell and B-shell groups. The treated shells can improve epidermal migration, the formation of granulation tissue, neovascular and hair follicles, and reducing scar tissue. Our mussel shell-derived membrane could have potential as a wound dressing and other biomedical uses.
Although the word wound sounds like a simple injury to tissue, individual's health status and other inherent factors may make it very complicated. Hence, wound healing has gained major attention in the healthcare. The biology wound healing is precise and highly programmed, through phases of hemostasis, inflammation, proliferation and remodeling. Current options for wound healing which includes, use of anti-microbial agents, healing promoters along with application of herbal and natural products. However, there is no efficient evidence-based therapy available for specific chronic wounds that can result in definitive clinical outcomes. Under co-morbid conditions, chronic would poses numerous challenges. Use of Complementary and Alternative Medicines (CAMs) in health care sector is increasing and its applications in wound management remains like to "separate the diamonds from ore." Attempts have been made to understand the wound at the molecular level, mainly through the analysis of signature genes and the influence of several synthetic and natural molecules on these. We have outlined a review of challenges in chronic wound healing and the role of CAMs in chronic wound management. The main focus is on the applications and limitations of currently available treatment options for a non-healing wound and the best possible alternates to consider. This information generates broader knowledge on challenges in chronic wound healing, which can be further addressed using multidisciplinary approach and combination therapies.
The purpose of this study was not only to evaluate the relative mRNA expression of interleukin-1β(IL-1β), cyclooxygenase2 (COX-2) and prostaglandin E2 (PGE2) by RT-PCR analysis but to observe pattern of edema by light microscopic and electron microscope after topical apply of hyaluronic acid in inflammation-guided mouse.
In man and domestic animals, scarring in the skin after trauma, surgery, burn or sports injury is a major medical problem, often resulting in adverse aesthetics, loss of function, restriction of tissue movement and/or growth and adverse psychological effects. Current treatments are empirical, unreliable and unpredictable: there are no prescription drugs for the prevention or treatment of dermal scarring. Skin wounds on early mammalian embryos heal perfectly with no scars whereas wounds to adult mammals scar. We investigated the cellular and molecular differences between scar-free healing in embryonic wounds and scar-forming healing in adult wounds. Important differences include the inflammatory response, which in embryonic wounds consists of lower numbers of less differentiated inflammatory cells. This, together with high levels of morphogenetic molecules involved in skin growth and morphogenesis, means that the growth factor profile in a healing embryonic wound is very different from that in an adult wound. Thus, embryonic wounds that heal without a scar have low levels of TGFbeta1 and TGFbeta2, low levels of platelet-derived growth factor and high levels of TGFbeta3. We have experimentally manipulated healing adult wounds in mice, rats and pigs to mimic the scar-free embryonic profile, e.g. neutralizing PDGF, neutralizing TGFbeta1 and TGFbeta2 or adding exogenous TGFbeta3. These experiments result in scar-free wound healing in the adult. Such experiments have allowed the identification of therapeutic targets to which we have developed novel pharmaceutical molecules, which markedly improve or completely prevent scarring during adult wound healing in experimental animals. Some of these new drugs have successfully completed safety and other studies, such that they have entered human clinical trials with approval from the appropriate regulatory authorities. Initial trials involve application of the drug or placebo in a double-blind randomized design, to experimental incision or punch biopsy wounds under the arms of human volunteers. Based on encouraging results from such human volunteer studies, the lead drugs have now entered human patient-based trials e.g. in skin graft donor sites. We consider the evolutionary context of wound healing, scarring and regeneration. We hypothesize that evolutionary pressures have been exerted on intermediate sized, widespread, dirty wounds with considerable tissue damage e.g. bites, bruises and contusions. Modem wounds (e.g. resulting from trauma or surgery) caused by sharp objects and healing in a clean or sterile environment with close tissue apposition are new occurrences, not previously encountered in nature and to which the evolutionary selected wound healing responses are somewhat inappropriate. We also demonstrate that both repair with scarring and regeneration can occur within the same animal, including man, and indeed within the same tissue, thereby suggesting that they share similar mechanisms and regulators. Consequently, by subtly altering the ratio of growth factors present during adult wound healing, we can induce adult wounds to heal perfectly with no scars, with accelerated healing and with no adverse effects, e.g. on wound strength or wound infection rates. This means that scarring may no longer be an inevitable consequence of modem injury or surgery and that a completely new pharmaceutical approach to the prevention of human scarring is now possible. Scarring after injury occurs in many tissues in addition to the skin. Thus scar-improving drugs could have widespread benefits and prevent complications in several tissues, e.g. prevention of blindness after scarring due to eye injury, facilitation of neuronal reconnections in the central and peripheral nervous system by the elimination of glial scarring, restitution of normal gut and reproductive function by preventing strictures and adhesions after injury to the gastrointestinal or reproductive systems, and restoration of locomotor function by preventing scarring in tendons and ligaments.
Since its introduction into clinical practice in 1967 by Charles Fox Jr., silver sulfadiazine has been the gold standard for topical burn therapy. The addition to it of hyaluronic acid, which forms a substantial part of the human tissue intercellular matrix, is aimed at overcoming one of its very few disadvantages, i.e. prolongation of the wound re-epithelialization process. Since both hyaluronic acid and silver sulfadiazine have been used in therapy for decades and their efficacy is well documented, a topical treatment combining these two agents was formulated. The aim of the study was to investigate the efficacy and tolerability of a cream containing a hyaluronic acid/silver sulfadiazine fixed combination, compared with silver sulfadiazine cream alone, for the treatment of superficial and deep second-degree burns in a prospective, double-blind, controlled clinical study. The findings of the study confirmed that the association of the two compounds in a new topical treatment significantly reduced the healing time and significantly accelerated the reduction of local edema occurring shortly after injury. Furthermore, this new hyaluronic acid and silver sulfadiazine formulation has proven to have favorable antibacterial, anti-edematous and local analgesic effects, together with a clear stimulatory activity on the re-epithelialization process. This product may, therefore, significantly enrich the assortment of topical medications available for the treatment of burns and skin defects of other origin.
In slow-healing wounds, i.e. those with little granulation tissue with deep necrotic tissue and exudation, complicated by inflammation, there is depolymerization and degradation of local mucopolysaccharides, especially hyaluronic acid. A local deficit of hyaluronic acid leads to insufficient regeneration of connective tissue, poor angiogenesis and deficient differentiation of histiocyte and fibroblast populations. Exogenous hyaluronic acid applied to a debrided wound keeps it moist and ensures a high concentration at the site of action. Hyaluronic acid stabilizes the clot matrix, attracts inflammatory, mesenchymal and epithelial cells into the wound area and enhances angiogenesis of the clot tissue. It also exerts an antiexudative, vasoprotective and fibrogenic action in inflamed tissues of slow-healing wounds. In this multicentre controlled study we evaluated the efficacy and safety of hyaluronic acid in 50 patients with venous leg ulcers in comparison with Dextranomer, the product of choice for this indication in France. Objective parameters, including the appearance and dimensions of the ulcer, improved significantly in both treatment groups. However, there was a faster and greater reduction in the ulcer dimensions following treatment with hyaluronic acid. Both treatments improved surrounding erythema, pain, oozing and necrosis but only hyaluronic acid caused a significant decrease in oedema. A greater number of positive efficacy judgements were seen in the hyaluronic acid group. The local tolerability of the two treatments was excellent. Hyaluronic acid is therefore a safe and effective treatment for patients with venous leg ulcers.
Honeybees were trained to find sugar water at a fixed location in front of a rectangular block or a gap in a row of rectangular
blocks aligned east-west. Bees learned to use both blocks and gaps to pinpoint a target place. In approach, the bees tended
to head directly towards the block but not the gap. In approaching the gap, they tended to approach the wall, and then fly
parallel to the wall until the gap was encountered. In approaching the block, they approached from varying directions. When
the width of the block or gap was doubled, bees still searched at the same perpendicular distance from the landmark. When
the height of the block was doubled, they searched farther away but not as far as double the distance on control tests, with
variations across individuals. Near the target area, the bees tended to face almost parallel to the gap or block, turned slightly
towards the landmark by 0–30°. In all setups, bees showed a tendency to search near the landmark, and to search on average
closer than the training distance. The results confirm the basic processes identified for landmark-based search in bees, but
show variations in how the steps are carried out.
Midgestation fetal wound healing is characterized by healing without fibrosis or scar formation. The mechanisms that underlie this remarkable process are mediated in part through a fetal wound extracellular matrix rich in hyaluronic acid. In this study a newly developed assay was used to determine the hyaluronic acid levels in fetal and adult wound fluid. Adult wound fluid had a rapid increase in hyaluronic acid, which peaked at 3 days and decreased to 0 by 7 days. In contrast levels of hyaluronic acid in fetal wound fluid increased rapidly and remained significantly elevated for 3 weeks. This prolonged presence of hyaluronic acid in the matrix of fetal wounds creates a 'permissive' wound environment that promotes fetal fibroblast movement and proliferation and inhibits cytodifferentiation. Such a matrix environment promotes healing by regeneration rather than by scarring. This observation has therapeutic implications. The prolonged application of hyaluronic acid or hyaluronate protein complexes to wounds in children or adults may modulate healing in a manner that makes the wounds more fetal-like.
The effect of hyaluronic acid (Ialugen cream) on acute skin reactions after radiotherapy, was assessed in a randomized, double-blind, placebo-controlled study.
Out of the 152 patients presenting with head and neck, breast or pelvic carcinomas and registered in the study, 134 cases-70 in the Ialugen group (IA) and 64 in the placebo group (PBO)-completed their IA or PBO treatment. At the time of randomisation, these two groups were balanced for sex, age, weight and height. The mean total dose of radiation given during the study was 60.6 +/- 10.9 Gy in the IA group and 64.3 +/- 10.8 Gy in the PBO group (P = 0.47).
Acute radio-epithelitis scores were significantly higher in the PBO group than in the IA group, starting from the control at week 3 and throughout the 6 weeks of treatment (P < 0.01 from week 3 to week 7; P < 0.05 at weeks 8 and 10). Likewise, the global efficacy judgement expressed, at the end of treatment, by both the physician and the patient showed a significant difference in favour of Ialugen (P < 0.01 and P < 0.05, respectively). There was no significant difference of tolerance between the IA and PBO treatments (P = 0.18 according to the physician and P = 0.42 from the patient's viewpoint).
The prophylactic use of a cream with hyaluronic acid is shown to reduce the incidence of high grade radio-epithelitis, suggesting an interesting role of the hyaluronic acid cream as supportive treatment to improve compliance and quality of life in patients undergoing radiation therapy.
Hyaluronan is a major carbohydrate component of the extracellular matrix and can be found in skin, joints, eyes and most other organs and tissues. It has a simple, repeated disaccharide linear copolymer structure that is completely conserved throughout a large span of the evolutionary tree, indicating a fundamental biological importance. Amongst extracellular matrix molecules, it has unique hygroscopic, rheological and viscoelastic properties. Hyaluronan binds to many other extracellular matrix molecules, binds specifically to cell bodies through cell surface receptors, and has a unique mode of synthesis in which the molecule is extruded immediately into the extracellular space upon formation. Through its complex interactions with matrix components and cells, hyaluronan has multifaceted roles in biology utilizing both its physicochemical and biological properties. These biological roles range from a purely structural function in the extracellular matrix to developmental regulation through effects of cellular behavior via control of the tissue macro- and microenvironments, as well as through direct receptor mediated effects on gene expression. Hyaluronan is also thought to have important biological roles in skin wound healing, by virtue of its presence in high amounts in skin. Hyaluronan content in skin is further elevated transiently in granulation tissue during the wound healing process. In this review, the general physicochemical and biological properties of hyaluronan, and how these properties may be utilized in the various processes of wound healing: inflammation, granulation and reepithelization, are presented.
Hyaluronic acid protects granulation tissue from oxygen free radical damage and stimulates wound healing, but its molecular weight prevents it from permeating the epidermal barrier A low molecular weight hyaluronic acid preparation is able to permeate the skin, but it is unknown whether or not it retains the scavenging effects of oxygen free radicals in granulation tissue. Our experiments were conducted in rats with excisional or incisional wounds. Wound contraction over 11 days and breaking strength on the fifth day were measured. Oxygen free radical production was induced by intraperitoneal administration of two different xenobiotics: phenazine methosulfate and zymosan. The wounds were treated topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In the incisional wound group, the effects of superoxide dismutase were also determined. Absolute controls received wounds and placebo but no xenobiotics. Wound healing was significantly slower in the xenobiotic group than in the control groups. These effects were strongly reduced by topical administration of low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by topically injected superoxide dismutase. Low molecular weight hyaluronic acid is effective as the native compound against oxygen free radicals. Its pharmacological effects through transdermal administration should be tested in appropriate models.
The glycosaminoglycan hyaluronic acid (HA), or hyaluronan, is a major component of the extracellular matrix of skin, joints, eye and many other tissues and organs. In spite of its simple structure, HA demonstrates remarkable rheological, viscoelastic and hygroscopic properties which are relevant for dermal tissue function. Biological activities in skin, however, are also due to its interaction with various binding proteins (hyaladherins). Due to an influence on signaling pathways, HA is involved in the wound-healing process and scarless fetal healing. Increased HA concentrations have been associated with inflammatory skin diseases. In clinical trials, topical application of HA improved wound healing; in particular, acute radioepithelitis, venous leg ulcers or diabetic foot lesions responded to HA treatment. Moreover, as a topical drug delivery system for diclofenac, an HA gel has recently been approved for the treatment of actinic keratoses. Finally, chemical modifications led to new HA derivates and biomaterials, which may be introduced into therapy in the future. Therefore, ongoing research offers new horizons for the therapeutic use of this glycosaminoglycan which has been regarded as an inert structural component until recently.
This multicenter, multinational, randomized, double-blind, controlled, parallel-group study, was designed to assess the efficacy and safety of a fixed combination topical medicinal product, containing 0.2% hyaluronic acid and 1% silver sulfadiazine (HA-SSD) (Connettivina Plus cream) versus 1% silver sulfadiazine cream alone (SSD), in the treatment of second-degree burns.
111 adult patients (age 18-75 years) of both sexes, with IIa-degree (superficial) and IIb-degree (deep dermal) burns, were randomized to receive HA-SSD or SSD. Treatments (approximately 5 g/100 cm2) were applied once a day until the wounds healed, but for no longer than 4 weeks. Burns had to have occurred within 48 hours from the start of treatment, be caused by thermal injury, and be confined to the trunk and/or upper and lower extremities.
Results showed that both the fixed combination HA-SSD, and SSD alone, were effective and well tolerated topical agents for the treatment of second-degree burns. All burns were healed except in one patient treated with SSD. It was also observed that the fixed combination HA-SSD caused a significantly more rapid re-epithelialization of burns, i.e. a shorter time to healing, than SSD alone. The difference recorded--4.5 days--was statistically significant (p = 0.0073).
The observed shorter time to healing caused by the fixed combination is clinically relevant and further demonstrates the wound healing activity of HA.
Hyaluronic acid (hyaluronan), a naturally occurring polymer within the skin, has been extensively studied since its discovery in 1934. It has been used in a wide range of medical fields as diverse as orthopedics and cosmetic surgery, but it is in tissue engineering that it has been primarily advanced for treatment. The breakdown products of this large macromolecule have a range of properties that lend it specifically to this setting and also to the field of wound healing. It is non-antigenic and may be manufactured in a number of forms, ranging from gels to sheets of solid material through to lightly woven meshes. Epidermal engraftment is superior to most of the available biotechnologies and, as such, the material shows great promise in both animal and clinical studies of tissue engineering. Ongoing work centers around the ability of the molecule to enhance angiogenesis and the conversion of chronic wounds into acute wounds.
This review discusses the multifaceted role of hyaluronic acid, focusing on the proliferative phase of wound healing. It considers the importance of achieving the right levels of this molecule, and the potential for future therapies.
Second-degree burns: a comparative, multicenter
- Costagliola M Agrosi
Costagliola M, Agrosi M. Second-degree burns: a comparative, multicenter,
Evaluation de l’activité et de la tolérance locale de Iasulet© crè;me et compresse dans le traitement des ulcè;res des membres inférieurs. Dossier d’enregistrement
- T Bruni
Propriétés pharmacologiques de l’acide hyalmonique
- Jm Bonnetblanc