Autologous skin substitute for hard-to-heal ulcers: retrospective analysis on safety, applicability, and efficacy in an outpatient and hospitalized setting.

Chronic ulcers ((arterio)venous, decubitus, or postoperative) have no tendency to heal within a period of at least 3 months despite optimal therapy according to internationally accepted guidelines. This retrospective study evaluates the safety and efficacy of an autologous, dermal-epidermal skin substitute (SS) for treating ulcers of various origins. Ulcers were treated within 7 Dutch centers over 5 years. Sixty-six ulcers (size: 0.75-150 cm²; duration: 0.25-32 years) with a follow-up time of 24 weeks after a single-skin substitute application were assessed. Wound-bed preparation consisted of vacuum-assisted-closure-therapy (5 days, hospitalized) or application of acellular dermis (5-7 days, outpatient). Time to heal, adverse events, and recurrence 1 year after complete healing were recorded. Complete ulcer healing occurred in 36 of 66 ulcers (55%) at 24 weeks. At that time point, a further 29% of ulcers showed decrease in ulcer size between 50 and 99%. No difference was observed between the hospitalized vs. outpatient treatment with complete healing. There were 32 of 36 healed ulcers that were available for follow-up 1 year after complete closure, of which 27 (84%) were still closed. Only two minor/moderate possibly related adverse events were recorded. This retrospective analysis shows that SS provides a safe and successful treatment for particularly chronic ulcers of various origins.

Comparison of autologous full-thickness gingiva and skin substitutes for wound healing.

Ideally tissue-engineered products should maintain the characteristics of the original tissue. For example, skin represents orthokeratinized epithelium and oral gingiva represents parakeratinized epithelium. The aim of this study was to develop an autologous full-thickness gingiva substitute suitable for clinical applications and to compare it with our autologous full-thickness skin substitute that is routinely used for healing chronic wounds. Autologous full-thickness skin and gingiva substitutes were constructed under identical culture conditions from 3-mm punch biopsies isolated from the upper leg or gingiva tissue, respectively. Both consisted of reconstructed epithelia on acellular dermis repopulated with fibroblasts. To compare the characteristics of the original and reconstructed tissue, differential morphological observations and expression of differentiation markers (keratins 6, 10, and 17 and stratum corneum precursors involucrin, loricrin, and SKALP) were determined. Skin and gingiva substitutes were transplanted onto therapy-resistant leg ulcers or tooth extraction sites in order to determine their effects on wound healing. The tissue-engineered constructs maintained many of the differential histological and immunohistochemical characteristics of the original tissues from which they were derived. The skin substitute was orthokeratinized, and the gingiva substitute was parakeratinized. Transplantation of skin (n = 19) and gingiva substitutes (n = 3) resulted in accelerated wound healing with no adverse effects. As identical culture systems were used to generate both the skin and gingiva substitutes, the differences observed in tissue (immuno)histology can be attributed to intrinsic properties of the tissues rather than to environmental factors (e.g., air or saliva). This study emphasizes the importance of closely matching donor sites with the area to be transplanted. Our results represent a large step forward in the area of clinical applications in oral tissue engineering, which have until now greatly lagged behind skin tissue engineering.