Martin Funk

The wound-healing process is a physiological response that begins after a disruption to the integrity of tissues present in the skin. To understand the intricacies involved in this process, many groups have tried to develop different in vitro models; however, the lack of a systemic response has, until this day, been the major barrier to the establishment of these models as the main study platform. Therefore, in vivo models are still the most common system for studying healing responses following different treatments, especially porcine models, which share several morphological similarities to the human skin. In this work, we developed a porcine excisional wound model and used semi-automated software as a strategy to generate quantitative morphometric results of healing responses by specific tissues and compartments. Our aim was to extract the most information from the model while producing reliable, reproducible, and standardized results. In order to achieve this, we established a 7-day treatment using a bacterial cellulose dressing as our standard for all the analyzed wounds. The thickness of the residual dermis under the wound (DUtW) bed was shown to influence the healing outcome, especially for the regeneration of epidermal tissue, including the wound closure rate. The analysis of the DUtW throughout the entire dorsal region of the animals opened up the possibility of establishing a map that will facilitate the experimental design of future works, increasing their standardization and reproducibility and ultimately reducing the number of animals needed. Thus, the developed model, together with the automated morphometric analysis approach used, offers the possibility to generate robust quantitative results with a rapid turnaround time while allowing the study of multiple extra morphometric parameters, creating a more holistic analysis.

Wound healing is a complex process that is still not fully understood despite extensive research. To address this, we aimed to design and characterize a standardized porcine model for the evaluation of wound healing, dressings, cell therapies, and pharmaceutical agents. Using a standardized approach, we examined the wound healing process in 1.2 mm-deep dermatome wounds at defined positions in 11 female pigs. Unlike previous studies that have only described/analyzed selected punch biopsies, we performed and described histological analyses along the complete wound length using quantitative morphometric methods. All animals remained fully healthy following surgery and showed no signs of infection. Our histopathological evaluation using a predetermined grading score and quantitative manual morphometry demonstrated the impact of different tissue sampling methods, sampling sites, and residual dermis thickness on wound healing. Our study presents a reproducible model for wound healing evaluation and demonstrates the usefulness of porcine models for assessing dermal and epidermal wound healing. The use of histological analyses over the complete wound length provides advantages over previous studies, leading to the possibility of a deeper understanding of the wound healing process. This model could potentially facilitate future research on novel wound dressings and local wound healing therapies.

Introduction: Pathogenic biofilms are an important factor for impaired wound healing, subsequently leading to chronic wounds. Nonsurgical treatment of chronic wound infections is limited to the use of conventional systemic antibiotics and antiseptics. Wound dressings based on bacterial nanocellulose (BNC) are considered a promising approach as an effective carrier for antiseptics. The aim of the present study was to investigate the antimicrobial activity of antiseptic-loaded BNC against in vitro biofilms. Materials and Methods: BNC was loaded with the commercially available antiseptics Prontosan^® and Octenisept^®. The silver-based dressing Aquacel^®Ag Extra was used as a positive control. The biofilm efficacy of the loaded BNC sheets was tested against an in vitro 24-hour biofilm of Staphylococcus aureus and Candida albicans and a 48-hour biofilm of Pseudomonas aeruginosa. In vivo tests using a porcine excisional wound model was used to analyze the effect of a prolonged treatment with the antiseptics on the healing process. Results: We observed complete eradication of S. aureus biofilm in BNC loaded with Octenisept^® and C. albicans biofilm for BNC loaded with Octenisept^® or Prontosan^®. Treatment with unloaded BNC also resulted in a statistically significant reduction in bacterial cell density of S. aureus compared to untreated biofilm. No difference on the wound healing outcome was observed for the wounds treated for seven days using BNC alone in comparison to BNC combined with Prontosan^® or with Octenisept^®. Conclusions: Based on these results, antiseptic-loaded BNC represents a promising and effective approach for the treatment of biofilms. Additionally, the prolonged exposure to the antiseptics does not affect the healing outcome. Prevention and treatment of chronic wound infections may be feasible with this novel approach and may even be superior to existing modalities.

A balanced and moist wound environment and surface increases the effect of various growth factors, cytokines, and chemokines, stimulating cell growth and wound healing. Considering this fact, we tested in vitro and in vivo water evaporation rates from the cellulose dressing epicite^hydro when combined with different secondary dressings as well as the resulting wound healing efficacy in a porcine donor site model. The aim of this study was to evaluate how the different rates of water evaporation affected wound healing efficacy. To this end, epicite^hydro primary dressing, in combination with different secondary dressing materials (cotton gauze, JELONET^◊, AQUACEL^® Extra ™, and OPSITE^◊ Flexifix), was placed on 3 × 3 cm-sized dermatome wounds with a depth of 1.2 mm on the flanks of domestic pigs. The healing process was analyzed histologically and quantified by morphometry. High water evaporation rates by using the correct secondary dressing, such as cotton gauze, favored a better re-epithelialization in comparison with the low water evaporation resulting from an occlusive secondary dressing, which favored the formation of a new and intact dermal tissue that nearly fully replaced all the dermis that was removed during wounding. This newly available evidence may be of great benefit to clinical wound management.

Burns affect millions every year and a model to mimic the pathophysiology of such injuries in detail is required to better understand regeneration. The current gold standard for studying burn wounds are animal models, which are under criticism due to ethical considerations and a limited predictiveness. Here, we present a three-dimensional burn model, based on an open-source model, to monitor wound healing on the epidermal level. Skin equivalents were burned, using a preheated metal cylinder. The healing process was monitored regarding histomorphology, metabolic changes, inflammatory response and reepithelialization for 14 days. During this time, the wound size decreased from 25% to 5% of the model area and the inflammatory response (IL-1β, IL-6 and IL-8) showed a comparable course to wounding and healing in vivo. Additionally, the topical application of 5% dexpanthenol enhanced tissue morphology and the number of proliferative keratinocytes in the newly formed epidermis, but did not influence the overall reepithelialization rate. In summary, the model showed a comparable healing process to in vivo, and thus, offers the opportunity to better understand the physiology of thermal burn wound healing on the keratinocyte level.