Regeneration of full-thickness wounds using collagen split grafts

Collagen-based skin substitutes are among the most promising materials to improve regeneration of full-thickness wounds. However, additional meshed grafts or cultured epidermal grafts are still required to create epidermal regeneration. To avoid this, we substituted collagen-based split grafts, i.e., grafts with a separated top and bottom layer, in a rat full-thickness wound model and compared regeneration with nontreated, open control wounds. We hypothesized that epidermal regeneration would occur in the split in between the two layers, with the top layer functioning as a clot/scab and the bottom layer as a dermal substitute. Two types of dermal sheep collagen (DSC) split grafts were tested: one with a top layer of noncrosslinked DSC (NDSC) and bottom layer of hexamethylenediisocyanate crosslinked DSC (HDSC), further called N/HDSC; and the second with both a top and bottom layer of HDSC (H/HDSC). With the N/HDSC split graft NDSC did not function as a sponge for formed exudate and as a consequence the split was not longer available to facilitate epidermal regeneration. In contrast, with the H/HDSC graft the split facilitated proliferation and differentiation of the epidermal cells in the proper way. With this graft, clot formation was restricted to the top layer, which was rejected after 8 weeks, while the bottom layer functioned during gradual degradation as a temporary matrix for the formation of autologous dermal tissue. H/HDSC strongly inhibited infiltration of myofibroblasts, resulting in a 30% wound contraction, while a 100% contraction was found with the open control wound. The results show that H/HDSC split-grafts function conforms to the hypothesis in regeneration of large, full-thickness wounds without further addition of seeded cells or use of meshed autografts.