Extensive penile skin necrosis after surgery for Peyronie's disease

The clinical case represents the surgical correction of postoperative complications in a patient with Peyronie's disease. The patient underwent flap corporoplasty using an autovein. The late postoperative period in the patient was complicated by extensive necrosis of the penile skin, which required repeated surgery as follows. The first stage of surgical treatment was performed by excision of necrotic tissues of the penile skin. Within 10 days of the postoperative period, chymotrypsin with an ointment containing dioxomethyltetrahydropyrimidine with chloramphenicol was applied to the penile wound surface to prepare the wound for subsequent skin autotransplantation. Further, within 5 days, the polymeric drainage sorbent «Aseptisorb DT» was applied to the wound surface until the wound was cleansed and granulation tissue was formed. The second stage of the surgical treatment performed penile skin replacement plasty with a free perforated skin graft taken from the patient's femoral surface.

Skin Immunity and Tolerance: Focus on Epidermal Keratinocytes Expressing HLA-G

Although the role of epidermal cells in skin regeneration has been extensively documented, their functions in immunity and tolerance mechanisms are largely underestimated. The aim of the present review was to outline the state of knowledge on resident immune cells of hematopoietic origin hosted in the epidermis, and then to focus on the involvement of keratinocytes in the complex skin immune networks acting in homeostasis and regeneration conditions. Based on this knowledge, the mechanisms of immune tolerance are reviewed. In particular, strategies based on immunosuppression mediated by HLA-G are highlighted, as recent advances in this field open up perspectives in epidermis-substitute bioengineering for temporary and permanent skin replacement strategies.

Surviving an Extensive Burn Injury Using Advanced Skin Replacement Technologies

There have been significant improvements in the technology available for treating extensive burns in the past decade. This case presents two unique, skin replacement technologies that were used to treat an 86% surface area flame burn in a pediatric patient. A temporary dermal replacement, known as “Novosorb™ Biodegradable Temporizing Matrix” was first used to stabilize the burn injury and remained in place for approximately three months. Given the large burn size and lack of available donor skin for grafting, a permanent skin replacement product known as “Self-Assembled Skin Substitute (SASS)” was then utilized to cover the burns. SASS is a novel technology that was developed to replace skin as an autologous skin graft and is currently available in Canada through a clinical trial for major burns. Ultimately, the concurrent use of these two technologies allowed for the unprecedented survival of a child following an extensive and life-threatening burn injury.

137 Maximal Harvest Density of Full-Thickness Skin Columns in Skin Replacement Therapy

Introduction Split-thickness skin grafts (STSGs) are the mainstay of skin replacement therapy but fail to adequately reproduce basic skin functions and subject patients to new, open wounds that can cause significant pain and scarring. Full-thickness skin grafts (FTSGs) have improved cosmetic outcomes and better recapitulate skin functions, but few sites can serve as donors and requirement for “take” is greater. Prior research has shown that full-thickness skin column (FTSC) harvest results in improved healing of the injured site and decreased morbidity of the donor site at 10% harvest density. This study aims to determine the maximal harvest density of FTSC donor sites. Methods Ten donor sites were created on the dorsum of anesthetized swine (Sus scrofa domestica). STSG donor sites were harvested with a dermatome (12/1000 inch) and compared to FTSC donor sites with the highest possible harvest ratio of sixteen 1.5mm-diameter skin columns/1cm2 (28% harvest density). Donor site morbidity was assessed via re-epithelialization, contraction, pigmentation, number of hair follicles, and scar thickness on post-burn day (PBD) 7, 14, 21, 28, 60, and 90. Results There were no significant differences in re-epithelialization or contraction between FTSC and STSG donor sites. STSG donor site pigmentation was significantly decreased as compared to control on all assessment days (p=0.0161, 0.0003, 0.0031, 0.0095, 0.0244, respectively), and remained significantly hypopigmented as compared to FTSC starting at PBD 14 (p< 0.0001). Pigmentation was decreased for FTSC donor sites at PBD 14 (p=0.0204) but significance was lost by PBD 21. Both FTSC and STSG donor sites showed significantly fewer hair follicles as compared to control at PBD 7 (p=0.0011, 0.0003, respectively). On PBD 21, STSG had significantly less hair follicles as compared to FTSC donor sites (p=0.0010). This resolved by PBD 28. FTSC scars were significantly thicker than both control and STSG at PBD 28 (p=0.0348, 0.0038, respectively) and PBD 60 (p=0.0174, 0.0329, respectively). This significance was lost by PBD 90. Conclusions No statistically significant differences were seen in re-epithelialization and contraction between FTSC and STSG donor sites. STSG were hypopigmented as compared to FTSC donor sites and had significantly less hair follicles at day 21. FTSC donor site scars were significantly thicker than STSG. Although decreased donor site morbidity has been observed at lower harvest densities (10%), these results were not seen at 28%, which likely exceeds the optimal harvest density.

139 Topical Exogenous Nutrient and Saline Supplementation to Improve Skin Graft Survival: From Lab to Operating Room

Introduction Skin grafting of poorly vascularized wound beds, (e.g. exposed fascia, tendon, or bone) is often a multi-stage procedure, resulting in persistent open wounds and long-term complications such as scarring and contracture. Single-stage skin replacement could mitigate these downsides. Here we present the addition of topical nutrients and negative-pressure wound therapy (NPWT) + saline instill to improve graft take, and a case report of treatment of a non-healing wound in a single-stage procedure. Methods Ex vivo, STSGs (12/1000ths in) were harvested from swine (Sus scrofa domestica) post-euthanasia and transferred into wells with distilled water, PBS, Tyrode’s Buffer, high (4.5g/L) and low (2g/L) glucose DMEM, EpiLife, or William’s E (WE) media for 7 days, followed by performance of biochemical analyses and immunohistochemistry. In vivo, 20 full-thickness 5cm-diameter excisional wounds on the dorsum of two anesthetized swine were treated with dermal substitutes (DS, 0.4mm, 0.8mm, 1.2mm, or 1.6mm thickness), STSG, and NPWT with or without intermittent saline instill (3x daily, 300mL, 15-minute soak). Re-epithelialization was assessed at day 7 and 14. Lastly, a chronic 800cm2 left knee wound was treated with NPWT + instill (every 3.5 hours, 80mL, 10-minute soak, 3-day duration) over a 12/1000ths inch STSG. Results DMEM with high glucose (DMEM-HG) and WE produced the most lactic acid and enzymatic carbonate. Lactate dehydrogenase activity was lowest with WE. DMEM-HG had the highest glucose consumption but the most unconsumed glucose, with WE resulting in the next highest amount. Immunohistochemistry showed DMEM-HG or WE had the most dividing and least dying cells. In the porcine model, DS of 0.8mm, 1.2mm, and 1.6mm thicknesses inhibited graft take significantly (p< 0.01, p=0.02, p< 0.01, respectively) for all NPWT alone wounds. Addition of saline instill showed significant improvement in graft take (p=0.03) for 0.8mm DS wounds. 1.2mm and 1.6mm DS wounds continued to show significantly decreased graft take (p=0.03 and p=0.02, respectively). All 0.4mm DS wounds performed similar to control. Clinically, following NPWT removal on post-op day 3, almost complete STSG take was observed without exudate, pus, or malodor within the wound bed. Conclusions While additional studies are ongoing to determine the optimal nutrient supplementation, WE performed the best overall thus far. In vivo, 0.8mm DS created a successful model of a poorly vascularized wound bed, as NPWT + instill overcame this thickness. The novel use of NPWT + instill treatment over STSG clinically shows promise to improve graft take in the future.

On skin substitutes for wound healing: Current products, limitations, and future perspectives

Cutaneous wound healing is a highly coordinated process involving numerous molecular pathways that regulate the function of specific skin cell types. One of the key decisions in acute and/or chronic wound healing management is to choose the skin substitute that, based on its composition and/or properties, may act as permanent skin replacement or temporary wound cover. The current products however are limited in their action, especially in the context of large chronic wounds or extensive second-/third-degree burns, due to the risk of developing infection, the limited vascularization, the inability to integrate to host tissue, and the lack in the healed area of skin apparatus responsible for temperature control, pigmentation, immune regulation, and nerve supply. In addition, the high cost of skin substitutes precludes their use in small- and moderate-size burns because they are economically impractical and protract the time to definitive wound closure. Thus, the need to develop cost-effective substitutes of high quality is imperative. The purpose of this review is to discuss current available products, their limitations and to provide some perspectives on future research toward generation of cost-effective, high-quality substitutes.

Advanced Hydrogels as Wound Dressings

Skin is the largest organ of the human body, protecting it against the external environment. Despite high self-regeneration potential, severe skin defects will not heal spontaneously and need to be covered by skin substitutes. Tremendous progress has been made in the field of skin tissue engineering, in recent years, to develop new skin substitutes. Among them, hydrogels are one of the candidates with most potential to mimic the native skin microenvironment, due to their porous and hydrated molecular structure. They can be applied as a permanent or temporary dressing for different wounds to support the regeneration and healing of the injured epidermis, dermis, or both. Based on the material used for their fabrication, hydrogels can be subdivided into two main groups—natural and synthetic. Moreover, hydrogels can be reinforced by incorporating nanoparticles to obtain “in situ” hybrid hydrogels, showing superior properties and tailored functionality. In addition, different sensors can be embedded in hydrogel wound dressings to provide real-time information about the wound environment. This review focuses on the most recent developments in the field of hydrogel-based skin substitutes for skin replacement. In particular, we discuss the synthesis, fabrication, and biomedical application of novel “smart” hydrogels.