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

Abstract

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.

Accelerated Healing of Full-Thickness Wounds by Genipin-Crosslinked Silk Sericin/PVA Scaffolds

“…Helbig et al [2009] reported that inflammatory cells are involved in the replacement of the necrotic zones and seem to be crucial for wound healing. However, the number of macrophages and giant cells is related to scar formation [Druecke et al, 2004]. High numbers of macrophages and giant cells are responsible for localized inflammatory reactions that could suppress further stages of wound healing and subsequently lead to scar formation [Druecke et al, 2004;Ratanavaraporn et al, 2012].…”

“…However, the number of macrophages and giant cells is related to scar formation [Druecke et al, 2004]. High numbers of macrophages and giant cells are responsible for localized inflammatory reactions that could suppress further stages of wound healing and subsequently lead to scar formation [Druecke et al, 2004;Ratanavaraporn et al, 2012]. Thus, the higher number of macrophages and giant cells in wounds treated with the genipin-crosslinked PVA scaffolds without sericin could delay wound healing compared with the genipin-crosslinked sericin/ PVA scaffolds.…”

An Overview of Methods for theIn VivoEvaluation of Tissue-Engineered Skin Constructs

“…In addition, they used a scale that was also used in other studies to systematically score for wound color, surface smoothness, and wound suppleness/stiffness. 169,177,180,198 Taken together, most studies provide a macroscopic but unsystematic description of wounds. To improve the comparison between studies, we recommend the use of a standard checklist: a subjective scar assessment tool could be used for this purpose, as described in Table 1.…”

“…Other studies used transparent papers to trace the wounds edges. 153,154,169 In some cases, the software used to calculate the wound area is specified. 134,137,142,146,147,150 However, differences in software is probably causing the least variation.…”

“…154,161 Comparable methods, including phase-contrast microscopy, were used on H&E-stained sections to assess collagen fiber maturation and/or orientation 169,177,180,198 and Lee et al used it to localize collagen and subsequently measured the staining intensity to quantify collagen deposition. 163 Windsor et al used orcein to stain (scaffold) collagen and a periodic acidSchiff (glycogen) staining to observe basement membrane formation (Fig.…”