Modulation of scar tissue formation using different dermal regeneration templates in the treatment of experimental full-thickness wounds

The recovery of skin function is the goal of each burn surgeon. Split-skin graft treatment of full-thickness skin defects leads to scar formation, which is often vulnerable and instable. Therefore, the aim of this study was to analyze wound healing and scar tissue formation in acute full-thickness wounds treated with clinically available biopolymer dermal regeneration templates. Full-thickness wounds (3 x 3 cm) on both flanks of Gottingen mini pigs (n= 3) were treated with split-thickness skin graft alone or in combination with a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) cross-linked-collagen scaffold, Integra, or a polyethyleneglycol terephthalate-polybutylene terephthalate (PEGT/PBT) scaffold. The wounds (n= 12 per group) were examined weekly for six weeks to evaluate graft take, contraction (planimetry), and cosmetic appearance. Histologic samples taken after one and six weeks were used to assess scaffold angiogenesis, biocompatibility, and scar tissue quality. In all wounds, one week postwounding graft take was between 93 and 100 percent. The control wound, treated with split-skin graft, showed little granulation tissue formation, whereas the EDC-collagen treated wounds showed two to three times more granulation tissue formation. The collagen scaffold was completely degraded within one week. The Integra and PEGT/PBT scaffolds showed angiogenesis only through two-thirds of the scaffold, which resulted in loss of integrity of the epidermis. Only basal cells survived, proliferated, and regenerated a fully differentiated epidermis within three weeks. Granulation thickness was comparable to collagen scaffold-treated wounds. After six weeks, control wounds showed a wound contraction of 27.2 +/- 6.1 percent, Integra-treated wounds 34.6 +/- 6.4 percent, collagen scaffold-treated wounds 38.1 +/- 5.0 percent, and PEGT/PBT scaffold-treated wounds 54.5 +/- 3.9 percent. The latter wounds had significantly more contraction than wounds of other treatment groups. Microscopically, the control and collagen scaffold-treated wounds showed an immature scar tissue that was two times thicker in the EDC-collagen treated wounds. The Integra-treated wounds showed nondegraded collagen scaffold fibers with partly de novo dermal tissue formation and partly areas with giant cells and other inflammatory cells. The PEGT/PBT scaffold was almost completely degraded. Scaffold particles were phagocytosized and degraded intracellularly by clusters of macrophages. The scar tissue was in the early phase of ECM remodeling. In conclusion, this study showed that the rate of dermal tissue formation and scarring is influenced by the rate of scaffold angiogenesis, degradation, and host response induced by the scaffold materials.