Modeling Wound Chronicity In Vivo: The Translational Challenge to Capture the Complexity of Chronic Wounds.

In an aging society with common lifestyle-associated health issues such as obesity and diabetes, chronic wounds pose a frequent challenge that physicians face in everyday clinical practice. Therefore, nonhealing wounds have attracted much scientific attention. Several in vitro and in vivo models have been introduced to deepen our understanding of chronic wound pathogenesis and amplify therapeutic strategies. Understanding how wounds become chronic will provide insights to reverse or avoid chronicity. Although choosing a suitable model is of utmost importance to receive valuable outcomes, an ideal in vivo model capturing the complexity of chronic wounds is still missing and remains a translational challenge. This review discusses the most relevant mammalian models for wound healing studies and provides guidance on how to implement the hallmarks of chronic wounds. It highlights the benefits and pitfalls of established models and maps out future avenues for research.

Unlocking longevity: the role of telomeres and its targeting interventions.

Average life expectancy has been steadily increasing in developed countries worldwide. These demographic changes are associated with an ever-growing social and economic strain to healthcare systems as well as society. The aging process typically manifests as a decline in physiological and cognitive functions, accompanied by a rise in chronic diseases. Consequently, strategies that both mitigate age-related diseases and promote healthy aging are urgently needed. Telomere attrition, characterized by the shortening of telomeres with each cell division, paradoxically serves as both a protective mechanism and a contributor to tissue degeneration and age-related ailments. Based on the essential role of telomere biology in aging, research efforts aim to develop approaches designed to counteract telomere attrition, aiming to delay or reduce age-related diseases. In this review, telomere biology and its role in aging and age-related diseases is summarized along with recent approaches to interfere with telomere shortening aiming at well- and healthy-aging as well as longevity. As aging research enters a new era, this review emphasizes telomere-targeting therapeutics, including telomerase activators and tankyrase inhibitors, while also exploring the effects of antioxidative and anti-inflammatory agents, along with indirectly related approaches like statins.

Pedicled Rectus Femoris Flap for Restoration of Suprapatellar Quadriceps Tendon and Defect Coverage after Multiple Reconstruction Attempts-A Case Report and Literature Review.

There is no unified approach for restoring the suprapatellar quadriceps tendon and covering tissue defects simultaneously. In this case report, we present the pedicled myocutaneous rectus femoris flap as one effective approach in two cases with extensive loss or impairment of the suprapatellar muscle-tendon structures after trauma-related suprapatellar quadriceps tendon rupture and multiple reconstruction attempts. Additionally, we provide a literature review of the reconstructive use of the functional pedicled myocutaneous rectus femoris flap. METHODS: Two male patients, 48 and 74 years old, with extensive loss or impairment of the suprapatellar muscle-tendon structures due to multiple reconstruction attempts, underwent restoration of the knee extension with a pedicled myocutaneous rectus femoris flap. RESULTS: Three months after reconstruction, both patients were able to walk freely, unaided. After a six-month follow-up, the free passive mobility of the knee joint was restored, and the active extension of the knee joint was possible in both patients. CONCLUSION: The authors conclude that the pedicled rectus femoris flap is a reliable method for the restoration of knee extension, with excellent functional results in cases of suprapatellar tendon lesions. Further to the functional restoration, this technique has the additional advantage of simultaneously achieving coverage of soft-tissue defects, while a direct closure of the donor site is possible. Elderly patients and patients with relevant comorbidities or multiple revisions may especially benefit from this technique.

Textured vs. Smooth Breast Implants Using the Jones Criteria-What Is the Currently Available Evidence for BIA-ALCL?: A Systematic Review.

Breast-Implant-Associated Anaplastic Large-Cell Lymphoma (BIA-ALCL) is a rare low-incidence type of T-cell non-Hodgkin lymphoma, arising in the capsule around breast implants, and predominantly associated with the use of macro-textured breast implants. The purpose of this study was to use an evidence-based approach to systematically identify clinical studies comparing smooth and textured breast implants in women with regard to the risk of developing BIA-ALCL. METHODS: A literature search in PubMed in April 2023 and the article reference list of the French National Agency of Medicine and Health Products decision from 2019 were screened for applicable studies. Only clinical studies where the Jones surface classification could be applied (required information: breast implant manufacturer) for comparison of smooth and textured breast implants were considered. RESULTS: From a total of 224 studies, no articles were included due to the lack of fit to the strict inclusion criteria. CONCLUSIONS: Based on the scanned and included literature, implant surface types in relation to the incidence of BIA-ALCL were not evaluated in clinical studies and data from evidence-based clinical sources plays a minor to no role in this context. An international database that combines breast implant-related data from (national, opt-out) medical device registries is, therefore, the best available option to obtain relevant long-term breast implant surveillance data on BIA-ALCL.

Human In Vitro Skin Models for Wound Healing and Wound Healing Disorders.

Skin wound healing is essential to health and survival. Consequently, high amounts of research effort have been put into investigating the cellular and molecular components involved in the wound healing process. The use of animal experiments has contributed greatly to the knowledge of wound healing, skin diseases, and the exploration of treatment options. However, in addition to ethical concerns, anatomical and physiological inter-species differences often influence the translatability of animal-based studies. Human in vitro skin models, which include essential cellular and structural components for wound healing analyses, would improve the translatability of results and reduce animal experiments during the preclinical evaluation of novel therapy approaches. In this review, we summarize in vitro approaches, which are used to study wound healing as well as wound healing-pathologies such as chronic wounds, keloids, and hypertrophic scars in a human setting.

Clinical Applications of Three-Dimensional Printing in Upper Extremity Surgery: A Systematic Review.

Three-dimensional printing for medical applications in surgery of the upper extremity has gained in popularity as reflected by the increasing number of publications. This systematic review aims to provide an overview of the clinical use of 3D printing in upper extremity surgery. METHODS: We searched the databases PubMed and Web of Science for clinical studies that described clinical application of 3D printing for upper extremity surgery including trauma and malformations. We evaluated study characteristics, clinical entity, type of clinical application, concerned anatomical structures, reported outcomes, and evidence level. RESULTS: We finally included 51 publications with a total of 355 patients, of which 12 were clinical studies (evidence level II/III) and 39 case series (evidence level IV/V). The types of clinical applications were for intraoperative templates (33% of a total of 51 studies), body implants (29%), preoperative planning (27%), prostheses (15%), and orthoses (1%). Over two third of studies were linked to trauma-related injuries (67%). CONCLUSION: The clinical application of 3D printing in upper extremity surgery offers great potential for personalized approaches to aid in individualized perioperative management, improvement of function, and ultimately help to benefit certain aspects in the quality of life.

The Impact of Thermal Stress on Cognition and the Use of Cooling Wear for Alleviation-An Explorative Study.

Increased ambient temperatures during the care of severely burned patients are essential for mitigating hypothermia and minimizing the impact of consecutive hypermetabolism. For involved medical staff, those conditions may lead to impaired concentration, possibly negatively affecting optimal patient care. Yet, alleviation strategies are lacking. As a novel coping strategy, cooling wear may be an effective means. This explorative study aimed to investigate the effect of high ambient temperatures on the concentration capacity and cooling wear to alleviate thermal stress. The effects of high ambient temperatures and the additional use of cooling wear on the concentration capacity of medical staff were investigated in six subjects during two simulated burn surgeries. Each individual served as his/her own control undergoing one simulation with and one without cooling wear. Concentration capacity was measured before and after each simulation with a standardized test. The results suggested that high ambient temperatures, as used in burn medicine, negatively affect human concentration capacity. The initial assessment of concentration capacity yielded homogenous values. After heat exposure, subjects wearing cooling wear showed a higher concentration capacity and a lower error rate compared to subjects without cooling wear. Summing up, temperature-related decrements in vigilance and performance among medical personnel may impair the patients' outcome. As an opportunity to withstand thermal stress and improve medical care and safety, cooling wear showed promising results and may be used as a heat alleviator. Burn medicine may particularly benefit from further development and rigorous investigation of cooling strategies.

Physical Activity on Telomere Length as a Biomarker for Aging: A Systematic Review.

BACKGROUND: Overall life expectancy continues to rise, approaching 80 years of age in several developed countries. However, healthy life expectancy lags far behind, which has, in turn, contributed to increasing costs in healthcare. One way to improve health and attenuate the socio-economic impact of an aging population is to increase overall fitness through physical activity. Telomere attrition or shortening is a well-known molecular marker in aging. As such, several studies have focused on whether exercise influences health and aging through telomere biology. This systematic review examines the recent literature on the effect of physical activity on telomere length (TL) and/or telomerase activity as molecular markers of aging. METHODS: A focused search was performed in the databases PubMed and Web of Science for retrieving relevant articles over the past ten years. The search contained the following keywords: exercise, sport, physical activity, fitness, sedentary, physical inactivity, telomere, telomere length, t/s ratio, and telomerase. PRISMA guidelines for systematic reviews were observed. RESULTS: A total of 43 articles were identified and categorized into randomized controlled trials (RCT), observational or interventional studies. RCTs (n = 8) showed inconsistent findings of increased TL length with physical activity in, e.g. obese, post-menopausal women. In comparison with a predominantly sedentary lifestyle, observational studies (n = 27) showed significantly longer TL with exercise of moderate to vigorous intensity; however, there was no consensus on the duration and type of physical activity and training modality. Interventional studies (n = 8) also showed similar findings of significantly longer TL prior to exercise intervention; however, these studies had smaller numbers of enrolled participants (mostly of high-performance athletes), and the physical activities covered a range of exercise intensities and duration. Amongst the selected studies, aerobic training of moderate to vigorous intensity is most prevalent. For telomere biology analysis, TL was determined mainly from leukocytes using qPCR. In some cases, especially in RCT and interventional studies, different sample types such as saliva, sperm, and muscle biopsies were analyzed; different leukocyte cell types and potential genetic markers in regulating telomere biology were also investigated. CONCLUSIONS: Taken together, physical activity with regular aerobic training of moderate to vigorous intensity appears to help preserve TL. However, the optimal intensity, duration of physical activity, as well as type of exercise still need to be further elucidated. Along with TL or telomerase activity, participants' fitness level, the type of physical activity, and training modality should be assessed at different time points in future studies, with the plan for long-term follow-up. Reducing the amount of sedentary behavior may have a positive effect of preserving and increasing TL. Further molecular characterization of telomere biology in different cell types and tissues is required in order to draw definitive causal conclusions on how physical activity affects TL and aging.

Non-invasive cooling wear as an effective means of reducing subcutaneous adipose tissue mass: an in-vivo study.

OBJECTIVE: The increasing prevalence of obesity is a major health problem worldwide. Several non-surgical treatments are now available that reduce body and subcutaneous fat mass. We aimed to determine the efficacy of mild cold for body mass reduction. METHODS: Novel cooling wear, which induces mild cooling via evaporation, was worn by 29 women with overweight for 4 weeks. Specifically, the participants wore a cooling waist belt and chaps for 1 hour per day. Non-invasive lipometry was used to determine their subcutaneous adipose tissue thicknesses, and the total weight loss, abdominal circumference, and body mass index (BMI) of the participants were measured. RESULTS: The participants achieved a significant total weight loss of 0.7 kg (0.9%), and significant reductions in BMI (0.2 kg/m2) and abdominal circumference (1.9 cm, 1.7%). Furthermore, there was a trend towards a reduction in abdominal subcutaneous fat thickness and a significant reduction in thickness of the anterior thigh was noted. A questionnaire-based evaluation indicated high usability and comfort of the cooling wear. CONCLUSION: There is a high and growing demand for non-invasive treatment strategies for obesity. Cooling wear represents a novel and promising approach that may be of particular use for individuals who do not require bariatric surgery.

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 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.

Resveratrol-Induced Signal Transduction in Wound Healing.

Resveratrol is a well-known polyphenol that harbors various health benefits. Besides its well-known anti-oxidative potential, resveratrol exerts anti-inflammatory, pro-angiogenic, and cell-protective effects. It seems to be a promising adjuvant for various medical indications, such as cancer, vascular, and neurodegenerative diseases. Additionally, resveratrol was shown to display beneficial effects on the human skin. The polyphenol is discussed to be a feasible treatment approach to accelerate wound healing and prevent the development of chronic wounds without the drawback of systemic side effects. Despite resveratrol's increasing popularity, its molecular mechanisms of action are still poorly understood. To take full advantage of resveratrol's therapeutic potential, a profound knowledge of its interactions with its targets is needed. Therefore, this review highlights the resveratrol-induced molecular pathways with particular focus on the most relevant variables in wound healing, namely inflammation, oxidative stress, autophagy, collagen proliferation and angiogenesis.

Thermal, Hyperspectral, and Laser Doppler Imaging: Non-Invasive Tools for Detection of The Deep Inferior Epigastric Artery Perforators-A Prospective Comparison Study.

Perforator flaps have become one of the leading procedures in microsurgical tissue transfer. Individual defects require a tailored approach to guarantee the most effective treatment. A thorough understanding of the individual vascular anatomy and the location of prominent perforators is of utmost importance and usually requires invasive angiography or at least acoustic Doppler exploration. In this study, we aimed at evaluating different non-invasive imaging modalities as possible alternatives for perforator location detection. After a cooling phase, we performed thermal, hyperspectral and Laser Doppler imaging and visually evaluated a possible detection of the perforator for a period of five minutes with an image taken every minute. We identified the most prominent perforator of the deep inferior epigastric artery by handheld acoustic Doppler in 18 patients. The detected perforator locations were then correlated. Eighteen participants were assessed with six images each per imaging method. We could show a positive match for 94.44%, 38.89%, and 0% of patients and 92.59%, 25.93%, and 0% of images for the methods respectively compared to the handheld acoustic Doppler. Sex, age, abdominal girth, and BMI showed no correlation with a possible visual detection of the perforator in the images. Therefore, thermal imaging can yield valuable supporting data in the individualized procedure planning. Future larger cohort studies are required to better assess the full potential of modern handheld thermal imaging devices.

Global burn care and the ideal burn dressing reloaded - A survey of global experts.

PURPOSE: Burn care is a highly relevant medical specialty in every part of the world. Different infrastructure, healthcare systems and access to medical supplies lead to different needs, treatment strategies and outcomes. A fundamental tool in a burn care provider's armamentarium is the use of different dressings. Several studies have investigated the question of the ideal burn dressing, but none could achieve a proper global perspective. With advanced dressings being on the rise, we conducted this study to get a global understanding of the actual use and idea of the ideal burn dressing. OBJECTIVE: The objective of this study was to investigate the understanding of an 'ideal burn dressing' on a global scale. MATERIALS AND METHODS: A questionnaire about burn care and the ideal burn dressing has been created and translated to five of the most spoken languages world-wide (English, Spanish, French, Chinese, Indonesian). It has been uploaded to an online survey platform and sent out to burn experts worldwide. The voluntary participation was possible for a period of four weeks. RESULTS: In total, 196 respondents from 49 countries participated in the study, yielding a response rate of 24.5%. The most important burn dressing characteristics in a cumulative ranking were (1) lack of adhesion (80.54%), (2) pain-free dressing change (79.87%), (3) requirement of fewer dressing changes, while in a linear ranking they were (1) anti-infective (35.14% 1st), pain-reduction (24.14% 2nd), and high absorbency (23.49% 3rd). Silver-based dressings are the most used dressings for superficial (45.21%) and deep (52.78%). 94.81% believe that the choice of burn dressing affects the outcome. CONCLUSION: This investigation has delivered valuable insights into the global perspective of the ideal burn dressing. Yet, the question of the ideal burn dressing is still inconclusive. Wound dressing research is of fundamental interest for patients, healthcare providers and healthcare systems.