Neovascularization during healing of wounds treated with dermal substitutes and fibrin glue in nude mice

Introduction: Dermal substitutes implanted into full-thickness skin wounds reduce wound contracture and improve cosmesis. These improvements depend upon optimal dermal vascularization. We hypothesized that dermal substitutes having native dermal composition would achieve such neovascularization more rapidly than synthetic dermal substitutes. We studied neovascularization in immunostained skin biopsies taken at weekly intervals from nude mice that had been implanted with different dermal substitutes and evaluated blood vessel ingrowth. Methods: Dermal matrices were implanted in full-thickness skin wounds on nude mice followed by fibrin glue (FG) with human keratinocytes (KC) Groups were: Integra, Alloderm, acellular dermal matrix (ADM), Dermalogen, Dermagraft, KCs + FG only, and FG only. Biopsies were performed weekly for 4 weeks. Immunostaining was performed for laminin and endoglin. Vessel counts were performed on immunostained sections in the superficial and deep dermis, in three regions: wound center, wound margin, and unwounded dermis. Results: The amount of vascularity in fully healed dermis was the same as that in unwounded dermis. However, extensive vascularity was seen at all time points in implanted Dermagraft and Dermalogen. Alloderm showed limited vascularity within 2 weeks post-op but this normalized by day 28. ADM and Integra showed rapid but controlled ingrowth of vessels from both the wound base and margins. Conclusions: We conclude that Dermagraft and Dermalogen underwent extensive granulation, whereas Alloderm underwent delayed vascularization. Alloderm, Integra, and ADM underwent progressive vessel ingrowth that was conducive to dermal regeneration and reepithelialization.