The Effect of Wound Dressings on a Bio-Engineered Human Dermo-Epidermal Skin Substitute in a Rat Model

Abstract

Autologous bio-engineered dermo-epidermal skin substitutes are a promising treatment for large skin defects such as burns. For their successful clinical application, the graft dressing must protect and support the keratinocyte layer and, in many cases, possess antimicrobial properties. However, silver in many antimicrobial dressings may inhibit keratinocyte growth and differentiation. The purpose of our study was to evaluate the effect of various wound dressings on the healing of a human hydrogel-based dermo-epidermal skin substitute in preparation for the first-in-human clinical trials. Human dermo-epidermal skin substitutes approved for clinical trials were produced under good manufacturing practice conditions, transplanted onto immuno-incompetent rats, and dressed with either Vaseline Gauze™ (Kendall Medtronic, Minneapolis, USA), Suprathel (PolyMedics Innovations GmbH, Denkendorf, Germany), Urgotul SSD (Urgo Medical, Shepshed, United Kingdom), Mepilex AG (Mölnlycke Health Care, Gothenburg, Sweden), or Acticoat™ (Smith&Nephew, Baar, Switzerland). Grafts were assessed clinically for take, epithelialization, and infection at 10 and 21 days post-transplantation, and histologically at 21 days. There were three subjects each in the Vaseline Gauze™ and Suprathel groups, and four subjects each in the Urgotul SSD, Mepilex AG, and Acticoat™ groups. For all samples, the take rate was 100% and the expected keratinocyte number, epithelialization and epidermal stratification were observed. All of the dressings in the current study were well tolerated by our human dermo-epidermal skin substitute. The tolerance of the silver-based dressings is particularly relevant given the high risk of bacterial contamination with large skin defects, and provides pivotal information as we embark on clinical trials for this novel skin substitute.

A Cultured Autologous Dermo-epidermal Skin Substitute for Full-Thickness Skin Defects: A Phase I, Open, Prospective Clinical Trial in Children

“…18,21,24 After plastic compression of the hydrogel and cultivation for 5 to 6 days, keratinocytes were seeded at a density of approximately 0.15 × 10 6 /cm 2 onto the surface of the graft. 18,[22][23][24] After additional cultivation, 18,22,23 grafts (Fig. 2, above, right) were shipped to the study site in a cell culture medium-filled tissue culture flask in a temperature-regulated transport box at 35 ± 5°C, to be grafted within 24 hours.…”

“…Punch biopsy specimens (3-mm diameter) were processed for histology and immunofluorescence as described previously. 24 Antibodies included anti-human K1 (Novus Biologicals, Littleton, Colo.), anti-human Lam332 (Santa Cruz, Nunningen, Switzerland), anti-human Tropoelastin (Elastin Products Co., Owensville, Mo. ), anti-human CD31 (Dako, Switzerland), and antihuman Keratin19 (Dako, Switzerland).…”

A Model to Study Wound Healing Over Exposed Avascular Structures in Rodents With a 3D-Printed Wound Frame

“…However, the primary challenge of wound contracture is a major limitation in rodents. Various models of wound chambers and rings have been described to prevent contracture and isolate the wounds to some extent 22–24,31–34 . However, these models including steel, titanium, and polycarbonate pieces are not readily affordable due to lack of commercially available materials and the need for skilled personnel to create the chambers.…”

Co-culture of ASCs/EPCs and dermal extracellular matrix hydrogel enhances the repair of full-thickness skin wound by promoting angiogenesis

“…The repair of large-scale full-thickness skin defects represents a challenging problem in skin tissue engineering [1,2]. At present, skin tissue engineering technology has made great progress, but there are still some obstacles, such as obvious scarring of new skin, large amount of tissue shrinkage, slow skinization speed, and difficulty in constructing full-thickness skin tissue [3][4][5].…”