Regenerative Therapies for Basal Thumb Arthritis-A Systematic Review.

Basal thumb arthritis is a painful and debilitating pathology that can severely reduce a patients' quality of life. Common therapies include oral pain control, local steroid injections and/or surgery. Yet, therapeutic data on long-term improvement and even cartilage repair are scarce. This review aims to present the currently available literature on novel therapies for basal thumb arthritis, including platelet-rich plasma (PRP), fat grafting and phototherapy, and investigate their potential efficacy. The entire OVID database and PubMed were searched for studies containing the topics PRP injection, lipofilling, laser treatment and regenerative treatment for carpometacarpal arthritis. Seven studies on the effect of fat tissue on basal thumb arthritis were found. Four authors reported on PRP injections, one RCT examined a combinational treatment of PRP and fat grafting, another phototherapy for the thumb joint and one prospective trial on chondrocyte transplantation was found. Pain improvement and decreased impairment were reported in the majority of PRP and/or fat grafting studies as well as after chondrocyte implantation. Phototherapy did not significantly improve the condition. This review revealed that only limited data on regenerative therapies for carpometacarpal arthritis are currently available, yet PRP and lipofilling show promising results and merit further investigation.

Platelet-Rich Plasma in Plastic Surgery: A Systematic Review.

Introduction: Platelet-rich plasma (PRP) is gaining popularity and is applied in a variety of clinical settings. This review aims to present and evaluate available evidence regarding the use of PRP in various applications in plastic surgery. Methods: PubMed, Web of Science, Medline, and Embase were searched using predefined MeSH terms to identify studies concerning the application of PRP alone or in combination with fat grafting for plastic surgery. The search was limited to articles in English or German. Animal studies, in vitro studies, case reports, and case series were excluded. Results: Of 50 studies included in this review, eleven studies used PRP for reconstruction or wound treatment, eleven for cosmetic procedures, four for hand surgery, two for burn injuries, five for craniofacial disorders, and 17 as an adjuvant to fat grafting. Individual study characteristics were summarized. Considerable variation in preparation protocols and treatment strategies were observed. Even though several beneficial effects of PRP therapy were described, significance was not always demonstrated, and some studies yielded conflicting results. Efficacy of PRP was not universally proven in every field of application. Conclusion: This study presents an overview of current PRP treatment options and outcomes in plastic surgery. PRP may be beneficial for some indications explored in this review; however, currently available data are insufficient and systematic evaluation is limited due to high heterogeneity in PRP preparation and treatment regimens. Further randomized controlled trials employing standardized protocols are warranted.

The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars-A New Model in the Duroc Pig.

Hypertrophic scars continue to be a major burden, especially after burns. Persistent inflammation during wound healing appears to be the precipitating aspect in pathologic scarring. The lack of a standardized model hinders research from fully elucidating pathophysiology and therapy, as most therapeutic approaches have sparse evidence. The goal of this project was to investigate the mechanisms of scar formation after prolonged wound inflammation and to introduce a method for generating standardized hypertrophic scars by inducing prolonged inflammation. Four wound types were created in Duroc pigs: full-thickness wounds, burn wounds, and both of them with induced hyperinflammation by resiquimod. Clinical assessment (Vancouver Scar Scale), tissue oxygenation by hyperspectral imaging, histologic assessment, and gene expression analysis were performed at various time points during the following five months. Native burn wounds as well as resiquimod-induced full-thickness and burn wounds resulted in more hypertrophic scars than full-thickness wounds. The scar scale showed significantly higher scores in burn- and resiquimod-induced wounds compared with full-thickness wounds as of day 77. These three wound types also showed relative hypoxia compared with uninduced full-thickness wounds in hyperspectral imaging and increased expression of HIF1a levels. The highest number of inflammatory cells was detected in resiquimod-induced full-thickness wounds with histologic features of hypertrophic scars in burn and resiquimod-induced wounds. Gene expression analysis revealed increased inflammation with only moderately altered fibrosis markers. We successfully created hypertrophic scars in the Duroc pig by using different wound etiologies. Inflammation caused by burns or resiquimod induction led to scars similar to human hypertrophic scars. This model may allow for the further investigation of the exact mechanisms of pathological scars, the role of hypoxia and inflammation, and the testing of therapeutic approaches.

Quality and Vitality of Autologous Fat Grafts Harvested by Different Techniques: A Clinical Comparison Study.

BACKGROUND: Unpredictable outcomes with autologous fat grafting due to reabsorption processes present a major challenge for healthcare providers and patients. A higher number of viable adipocytes is considered to result in a higher volume being retained. Although various adverse factors have been extensively researched, other potential parameters have been less investigated or even neglected. OBJECTIVE: The aim of this study was to investigate the harvesting process of adipose tissue as the primary cause of cell damage and to determine the risk factors associated with low cell survival. METHODS: Thirty-nine male and female subjects undergoing planned elective liposuction or abdominoplasty were enrolled. Forty-seven lipoaspirates harvested by different liposuction techniques were analyzed. RNA isolation and real-time polymerase chain reaction was performed to elucidate differences in the expression of various adipocyte markers. Furthermore, scanning electron microscopy was performed on various samples to determine the cell damage caused by the different techniques. RESULTS: A statistically significant lower expression of peroxisome proliferator-activated receptor γ was detected in subjects with a higher BMI. A trend towards a lower expression of perilipin 1 in lipoaspirates harvested by a super wet + ultrasound technique, compared with dry and super wet techniques, was shown. The lowest level of cell damage determined from scanning electron microscopy images was in lipoaspirates harvested by the super wet + ultrasound technique, and this level was statistically significantly different from those obtained by the 2 other techniques. CONCLUSIONS: Optimization of the outcome in autologous fat grafting may be feasible by targeting and optimizing the harvesting process as a main risk factor for impaired adipocyte viability. Ultrasound-assisted liposuction might be considered a suitable harvesting technique.

Autologous Fat Grafting in Reconstructive Breast Surgery: Clinically Relevant Factors Affecting the Graft Take.

BACKGROUND: Autologous fat grafting is an effective tool for soft tissue augmentation in reconstructive breast surgery. Despite the major advantages of this minimally invasive approach, the unpredictability of graft survival presents challenges. OBJECTIVES: No clear consensus on the optimal technique has yet been published and well-defined prospective studies investigating impairing factors are lacking. This aim of this study was to generate valuable fundamental data. METHODS: Ten female patients undergoing elective autologous fat grafting after nipple-sparing mastectomy were enrolled. Punch biopsies and lipoaspirates were collected from the harvest site for histologic, gene expression, and scanning electron microscopic analysis. Noninvasive Lipometer measurements determining the subcutaneous adipose tissue thickness at the graft site were used to calculate the respective take rate. Patient- and surgery-related data were acquired and correlated with the take rate. RESULTS: A statistically relevant correlation between the take rate and the existing mean subcutaneous adipose tissue thickness at the grafted breast prior to surgery was observed. An approximate correlation was identified regarding the number of previous grafting sessions, body weight, and BMI. No statistically significant correlation was demonstrated for age, harvest site, or the mean adipocyte size. A lower level of cell damage was observed in scanning electron microscopic samples of washed lipoaspirates; and a strong indirect correlation with the expression of the adipocyte markers FABP4 and PLIN1 was apparent. CONCLUSIONS: Factors correlating to the take rate were identified. Future studies investigating the clinical relevance of each impairing factor are essential to contribute to the optimization of this valuable method.

The impact of resveratrol on skin wound healing, scarring, and aging.

Resveratrol is a well-known antioxidant that harbours many health beneficial properties. Multiple studies associated the antioxidant, anti-inflammatory, and cell protective effects of resveratrol. These diverse effects of resveratrol are also potentially involved in cutaneous wound healing, scarring, and (photo-)aging of the skin. Hence, this review highlighted the most relevant studies involving resveratrol in wound healing, scarring, and photo-aging of the skin. A systematic review was performed and the database PubMed was searched for suitable publications. Only original articles in English that investigated the effects of resveratrol in wound healing, scarring, and (photo-)aging of the skin were analysed. The literature search yielded a total of 826 studies, but only 41 studies met the inclusion criteria. The included studies showed promising results that resveratrol might be a feasible treatment approach to support wound healing, counteract excessive scarring, and even prevent photo-aging of the skin. Resveratrol represents an interesting and promising novel therapy regime but to confirm resveratrol-associated effects, more evidence based in vitro and in vivo studies are needed.

The successful use of polylactide wound dressings for chronic lower leg wounds: A retrospective analysis.

Chronic wounds are a challenging medical entity for patients, medical professionals and healthcare systems. Frequently, patients present themselves to wound specialists after months or even years of unsuccessful treatment. Recent developments have resulted in a multitude of different advanced wound dressings created to treat complex, chronic wounds, one of which is the polylactide dressing Suprathel. This study aimed at investigating the healing potential of Suprathel in chronic wounds and differentiating between old and "young", diabetic and non-diabetic chronic wounds. A prospective, multicentric, non-controlled intervention study was conducted, treating patients with chronic lower leg ulcers (>3 months) with Suprathel and assessing them weekly. Afterwards, a retrospective analysis was performed analysing the wound size initially, after 4 and after 8 weeks of treatment. Furthermore, a differentiation between diabetic and non-diabetic, and chronic wounds older and younger than 12 months, was assessed. A significant reduction in wound size was observed in the study population after 8 weeks of treatment. The effect size in the diabetic wound and the old chronic wound group even reached more than one, with the other groups still showing a large effect of the intervention. This study shows that Suprathel is a valuable tool in the armamentarium of a wound specialist. Not only could we show a positive effect on chronic wounds, we could even demonstrate a significant wound size reduction in chronic wounds of old and young, as well as diabetic wounds, with the treatment of older chronic and diabetic wounds yielding an even larger effect size. Further randomised, controlled studies are necessary to show the full potential of advanced wound dressing materials in large patient cohorts.

The Use of Acellular Fish Skin Grafts in Burn Wound Management-A Systematic Review.

Background and Objectives: Burn wound healing and management continues to be a major challenge for patients and health care providers resulting in a considerable socio-economic burden. Recent advances in the development of applicable xenografts as an alternative to split-thickness skin grafts have allowed for the development of acellular fish skin. Acellular fish skin acts as a skin substitute, reducing inflammatory responses and advancing proinflammatory cytokines that promote wound healing. Due to these beneficial wound healing properties, acellular fish skin might represent an effective treatment approach in burn wound management. Materials and Methods: A systematic review of the literature, up to March 2022, was conducted using the electronic databases PubMed and Web of Science. Titles and abstracts were screened for the following key terms (variably combined): "fish skin", "fish skin grafts", "acellular fish skin", "Omega3 Wound matrix", "xenograft", "burn injury", "burns". Results: In total, 14 trials investigating the effects of acellular fish skin in burn wounds or split-thickness donor sites were determined eligible and included in the present review. Existing evidence on the use of acellular fish skin indicates an acceleration of wound healing, reduction in pain and necessary dressing changes as well as treatment-related costs and improved aesthetic and functional outcomes compared to conventional treatment options. Conclusions: Acellular fish skin xenografts may represent an effective, low-cost alternative in treatment of superficial- and partial-thickness burns. However, results mainly originate from preclinical and small cohort studies. Future larger cohort studies are warranted to elucidate the full potential of this promising approach.

In Vivo Models for Hypertrophic Scars-A Systematic Review.

Backgroundand Objectives: Hypertrophic scars following surgeries or burns present a serious concern for many patients because these scars not only lead to an aesthetical but also to a functional and psychological burden. Treatment of hypertrophic scars is challenging because despite various treatment options, a low level of evidence hinders preference of any specific treatment plan. To properly identify new therapeutic approaches, the use of in vivo models remains indispensable. A gold standard for hypertrophic scars has not been established to date. This review aims at giving a comprehensive overview of the available in vivo models. Materials and Methods: PubMed and CINAHL were queried for currently existing models. Results: Models with mice, rats, rabbits, pigs, guinea pigs and dogs are used in hypertrophic scar research. Rodent models provide the advantage of ready availability and low costs, but the number of scars per animal is limited due to their relatively small body surface, leading to a high number of test animals which should be avoided according to the 3Rs. Multiple scars per animal can be created in the guinea pig and rabbit ear model; but like other rodent models, these models exhibit low transferability to human conditions. Pig models show a good transferability, but are cost-intensive and require adequate housing facilities. Further, it is not clear if a currently available pig model can deliver clinical and histological features of human hypertrophic scars concurrently. Conclusions: None of the analyzed animal models can be clearly recommended as a standard model in hypertrophic scar research because the particular research question must be considered to elect a suitable model.

Platelet-rich plasma for striae distensae: What do we know about processed autologous blood contents for treating skin stretchmarks?-A systematic review.

Striae distensae, also known as stretch marks, particularly associated with female sex, pregnancy, obesity, and/or hormonal change, are linear bands of benign dermal lesions. Although not posing any health risk, aesthetically unpleasing stretch marks can cause significant psychological distress among those affected. In abundance of therapeutic approaches, some literature sources proclaim platelet-rich plasma to be a promising treatment modality for striae distensae. We aimed to shed some light on the current literature evidence of platelet-rich plasma for treating stretch marks and performed an English literature analysis with two independent reviewers in accordance with PRISMA guidelines searching the PubMed and Web of Science databases in June 2019. Of the 12 found studies, 6 matched inclusion criteria. With no control groups in two, just two other reports used intraindividual comparisons, and all but one publication performed histopathological assessments. All studies observed clinical and subjective improvements without using validated scores or patient-reported outcome measures (PROMs). The main findings were that multiple treatments with platelet-rich plasma demonstrated increased epidermal thickness, rete ridges formation, and collagen/elastin formation, while decreasing the inflammatory cell infiltrate. The current literature evidence supporting the use of platelet-rich plasma for striae distensae is poor. We propose in this review an outline for a study protocol with intraindividual control groups, standardised scores, validated PROMs, and participant incentives to enhance the scientific power in future clinical trials.

Historical Evolution of Skin Grafting-A Journey through Time.

Autologous skin grafting was developed more than 3500 years ago. Several approaches and techniques have been discovered and established in burn care since then. Great achievements were made during the 19th and 20th century. Many of these techniques are still part of the surgical burn care. Today, autologous skin grafting is still considered to be the gold standard for burn wound coverage. The present paper gives an overview about the evolution of skin grafting and its usage in burn care nowadays.

Made in Germany: A Quality Indicator Not Only in the Automobile Industry But Also When It Comes to Skin Replacement: How an Automobile Textile Research Institute Developed a New Skin Substitute.

Successful research and development cooperation between a textile research institute, the German Federal Ministry of Education and Research via the Center for Biomaterials and Organ Substitutes, the University of Tübingen, and the Burn Center of Marienhospital, Stuttgart, Germany, led to the development of a fully synthetic resorbable temporary epidermal skin substitute for the treatment of burns, burn-like syndromes, donor areas, and chronic wounds. This article describes the demands of the product and the steps that were taken to meet these requirements. The material choice was based on the degradation and full resorption of polylactides to lactic acid and its salts. The structure and morphology of the physical, biological, and degradation properties were selected to increase the angiogenetic abilities, fibroblasts, and extracellular matrix generation. Water vapor permeability and plasticity were adapted for clinical use. The available scientific literature was screened for the use of this product. A clinical application demonstrated pain relief paired with a reduced workload, fast wound healing with a low infection rate, and good cosmetic results. A better understanding of the product's degradation process explained the reduction in systemic oxidative stress shown in clinical investigations compared to other dressings, positively affecting wound healing time and reducing the total area requiring skin grafts. Today, the product is in clinical use in 37 countries. This article describes its development, the indications for product growth over time, and the scientific foundation of treatments.

Oxygen, pH, Lactate, and Metabolism-How Old Knowledge and New Insights Might Be Combined for New Wound Treatment.

Over time, we have come to recognize a very complex network of physiological changes enabling wound healing. An immunological process enables the body to distinguish damaged cells and begin a cleaning mechanism by separating damaged proteins and cells with matrix metalloproteinases, a complement reaction, and free radicals. A wide variety of cell functions help to rebuild new tissue, dependent on energy provision and oxygen supply. Like in an optimized "bio-reactor," disturbance can lead to prolonged healing. One of the earliest investigated local factors is the pH of wounds, studied in close relation to the local perfusion, oxygen tension, and lactate concentration. Granulation tissue with the wrong pH can hinder fibroblast and keratinocyte division and proliferation, as well as skin graft takes. Methods for influencing the pH have been tested, such as occlusion and acidification by the topical application of acidic media. In most trials, this has not changed the wound's pH to an acidic one, but it has reduced the strong alkalinity of deeper or chronic wounds. Energy provision is essential for all repair processes. New insights into the metabolism of cells have changed the definition of lactate from a waste product to an indispensable energy provider in normoxic and hypoxic conditions. Neovascularization depends on oxygen provision and lactate, signaling hypoxic conditions even under normoxic conditions. An appropriate pH is necessary for successful skin grafting; hypoxia can change the pH of wounds. This review describes the close interconnections between the local lactate levels, metabolism, healing mechanisms, and pH. Furthermore, it analyzes and evaluates the different possible ways to support metabolism, such as lactate enhancement and pH adjustment. The aim of wound treatment must be the optimization of all these components. Therefore, the role of lactate and its influence on wound healing in acute and chronic wounds will be assessed.

Porcine Xenograft and Epidermal Fully Synthetic Skin Substitutes in the Treatment of Partial-Thickness Burns: A Literature Review.

Background and Objectives: Porcine xenografts have been used successfully in partial thickness burn treatment for many years. Their disappearance from the market led to the search for effective and efficient alternatives. In this article, we examine the synthetic epidermal skin substitute Suprathel® as a substitute in the treatment of partial thickness burns. Materials and Methods: A systematic review following the PRISMA guidelines has been performed. Sixteen Suprathel® and 12 porcine xenograft studies could be included. Advantages and disadvantages between the treatments and the studies' primary endpoints have been investigated qualitatively and quantitatively. Results: Although Suprathel had a nearly six times larger TBSA in their studies (p < 0.001), it showed a significantly lower necessity for skin grafts (p < 0.001), and we found a significantly lower infection rate (p < 0.001) than in Porcine Xenografts. Nonetheless, no significant differences in the healing time (p = 0.67) and the number of dressing changes until complete wound healing (p = 0.139) could be found. Both products reduced pain to various degrees with the impression of a better performance of Suprathel® on a qualitative level. Porcine xenograft was not recommended for donor sites or coverage of sheet-transplanted keratinocytes, while Suprathel® was used successfully in both indications. Conclusion: The investigated parameters indicate that Suprathel® to be an effective replacement for porcine xenografts with even lower subsequent treatment rates. Suprathel® appears to be usable in an extended range of indications compared to porcine xenograft. Data heterogeneity limited conclusions from the results.

Evidence-based therapy in hypertrophic scars: An update of a systematic review.

Hypertrophic scars are still a major burden for numerous patients, especially after burns. Many treatment options are available; however, no evidence-based treatment protocol is available with recommendations mostly emerging from experience or lower quality studies. This review serves to discuss the currently available literature. A systematic review was performed and the databases PubMed and Web of Science were searched for suitable publications. Only original articles in English that dealt with the treatment of hypertrophic scars in living humans were analyzed. Further, studies with a level of evidence lower than 1 as defined by the American Society of Plastic Surgeons were excluded. After duplicate exclusion, 1638 studies were screened. A qualitative assessment yielded 163 articles eligible for evidence grading. Finally nine studies were included. Four of them used intralesional injections, four topical therapeutics and one assessed the efficacy of CO2 -laser. Intralesional triamcinolone + fluorouracil injections, and topical pressure and/or silicone therapy revealed significant improvements in terms of scar height, pliability, and pigmentation. This systematic review showed that still few high-quality studies exist to evaluate therapeutic means and their mechanisms for hypertrophic scars. Among these, most of them assessed the efficacy of intralesional triamcinolone injections with the same treatment protocol. Intralesional injection appears to be the best option for hypertrophic scar treatment. Future studies should focus on a possible optimization of infiltrative therapies, consistent end-point evaluations, adequate follow-up periods, and possibly intraindividual treatments.

DNA repair enzymes in sunscreens and their impact on photoageing-A systematic review.

BACKGROUND: DNA damage is one of the main factors responsible for photoageing and is predominantly attributed to ultraviolet irradiation (UV-R). Photoprotection by conventional sunscreens is exclusively prophylactic, and of no value, once DNA damage has occurred. As a result, the demand for DNA repair mechanisms inhibiting, reversing or delaying the pathologic events in UV-exposed skin has sparked research on anti-photoageing and strategies to improve the effect of conventional sunscreens. This review provides an overview of recent developments in DNA repair enzymes used in sunscreens and their impact on photoageing. METHODS: A systematic review of the literature, up to March 2019, was conducted using the electronic databases, PubMed and Web of Science. Quality assessment was carried out using the Newcastle-Ottawa scale (NOS) to ensure inclusion of adequate quality studies only (NOS > 5). RESULTS: Out of the 352 publications, 52 were considered relevant to the key question and included in the present review. Two major enzymes were found to play a major role in DNA damage repair in sunscreens: photolyase and T4 endonuclease V. These enzymes are capable of identifying and removing UV-R-induced dimeric photoproducts. Clinical studies revealed that sunscreens with liposome-encapsulated types of photolyase and/or T4 endonuclease V can enhance these repair mechanisms. CONCLUSION: There is a lack of randomized controlled trials demonstrating the efficacy of DNA repair enzymes on photoageing, or a superiority of sunscreens with DNA repair enzymes compared to conventional sunscreens. Further studies are mandatory to further reveal pathogenic factors of photoageing and possible therapeutic strategies against it.

Management of Severe Burn Wounds Colonized With Multi-resistant Pseudomonas aeruginosa and Fusarium Using Marine Omega3 Wound Matrix in a Female Victim of War.

War-related burns are common injuries, also among the civilian population. Additional trauma such as fractures or shrapnel wounds may add significant morbidity. Burn injuries in war zones are furthermore frequently undertreated and hence prone to complications. We report a case of a young female victim of war, whose severely infected burn wounds could be successfully healed using a combination of targeted antimicrobial therapy, wound conditioning using decellularized fish skin, and subsequent skin grafting.

Development of a Cellular Assay as a Personalized Model for Testing Chronic Wound Therapeutics.

Exudates of nonhealing wounds contain drivers of pathogenicity. We utilized >800 exudates from nonhealing and healing wounds of diverse etiologies, collected by 3 different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to (i) differentiate between healing and nonhealing wounds, (ii) follow the healing process of individual patients, and (iii) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically nonhealing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo nonhealing wound exudates revealed an induction of inflammatory cytokine and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of nonhealing wounds. Testing the wound therapeutics, PDGF and silver sulfadiazine, yielded responses in line with clinical experience and indicates the usefulness of the assay to search for and profile new therapeutics.

Undergraduate Skills Training in Pandemic Times: Where Is the Future of Medical Education?

BACKGROUND: The COVID-19 pandemic forced medical programs to rapidly switch to remote teaching from scratch, impacting hands-on skills training. This study compared the efficacy of a hybrid online format to a regular in-person session for a mandatory surgical skills class. METHODS: Third-year undergraduate medical students attending the surgical skills class in the winter semester of 2020/21 at the Medical University of Graz were randomly assigned to either the hybrid or in-person class, depending on their course schedule and government regulations. The hybrid class involved online videos, one-on-one peer tutoring, and an Objective Structured Clinical Examination (OSCE). Pre- and post-class self-assessments were conducted to evaluate their theoretical and practical knowledge of a single interrupted suture. RESULTS: The study included 85 students in the regular in-person class and 50 in the hybrid class. A pre-class assessment revealed higher self-assessments in the hybrid class for theoretical and practical knowledge, but a post-class assessment showed no significant difference. The advantages and disadvantages of both modalities were identified, providing valuable insights for future curriculum development. CONCLUSIONS: Both teaching modes were effective for undergraduate surgical skills training. This study recommends implementing positive aspects of both the hybrid and in-person formats while recognizing their respective limitations.