Partial dermal regeneration is induced by biodegradable collagen-glycosaminoglycan grafts

We have sequentially documented the early morphologic events that result in partial regeneration of the adult guinea pig dermis. This phenomenon occurs when a full-thickness skin wound is grafted with a highly specific collagen-glycosaminoglycan (CG) copolymer which has been seeded with autologous dermal and epidermis cells (Yannas IV, Lee E, Orgill DP, Skrabut EM, Murphy GF, Proc Natl Acad Sci USA 86:933-937, 1989). By day 7, ultrastructural analysis disclosed highly organized associations between mononuclear cells and CG fibers involving prominent extension of pseudopod-like processes toward the fiber surface. Spatial organization of cells was not evident in ungrafted wounds. By day 10, more than 50% of the CG grafts had been degraded and extensive neovascularization was observed in various stages of formation. By day 14, dermal fibroblasts in the graft site demonstrated random alignment of long axes, and a minor fraction (less than 10%) exhibited features of myofibroblasts. A majority (greater than 50%) of dermal fibroblasts in ungrafted wounds were identified as myofibroblasts at this time, and their axes were regularly aligned in parallel with the overlying epidermal layer. Scattered CG copolymer fragments were engulfed by macrophages by day 14, and complete dissolution occurred by day 21. Dermal blood vessels formed a discrete, subepidermal plexus oriented parallel to the epidermal plane by days 14 to 17 in grafted wound beds but not in ungrafted ones. Progressive, randomly oriented collagen deposition occurred at graft sites during the 1st year, whereas collagen fibers in ungrafted wounds were aligned in a horizontal plane atypical of a forming scar. By 1 year, the graft sites resembled normal dermis, with well-defined dermal papillae, normal anastomosing superficial vasculature, nerve fibers, and random collagen fiber morphology. Wound sites at this juncture resembled a mature scar, with a flattened dermal-epidermal interface; rare and disorganized vessels and nerves; and collagen fibers parallel to the epidermis. This investigation demonstrates the critical importance of highly specific extracellular matrix in induction of dermal morphogenesis.