Mechanisms underlying heterologous skin scaffold-mediated tissue remodeling.

Kallyne K O Mimura,Tahera Ansari,Karin V Greco,Rebecca Greco,Andréia R Moraes,Sonia M Oliani,Aline C Miranda,Paul Sibbons

doi:10.1038/srep35074

Abstract

Biocompatibility of two newly developed porcine skin scaffolds was assessed after 3, 14, 21 and 90 days of implantation in rats. Both scaffolds showed absence of cells, preservation of ECM and mechanical properties comparable to non-decellularised skin before implantation. Host cell infiltration was much prominent on both scaffolds when compared to Permacol (surgical control). At day 3, the grafts were surrounded by polymorphonuclear cells, which were replaced by a notable number of IL-6-positive cells at day 14. Simultaneously, the number of pro-inflammatory M1-macrophage was enhanced. Interestingly, a predominant pro-remodeling M2 response, with newly formed vessels, myofibroblasts activation and a shift on the type of collagen expression was sequentially delayed (around 21 days). The gene expression of some trophic factors involved in tissue remodeling was congruent with the cellular events. Our findings suggested that the responsiveness of macrophages after non-crosslinked skin scaffolds implantation seemed to intimately affect various cell responses and molecular events; and this range of mutually reinforcing actions was predictive of a positive tissue remodeling that was essential for the long-standing success of the implants. Furthermore, our study indicates that non-crosslinked biologic scaffold implantation is biocompatible to the host tissue and somehow underlying molecular events involved in tissue repair.

Highlights

Designed as a skin substitute, both epidermal and dermal acellular matrices obtained after different decellularisation processes have been under investigation for over a decade[1,2,3,4,5]
DNA quantification showed that approximately 90% of nuclear material was depleted after both decellularisation protocols, with no visible DNA on the electrophoresis gel following staining by ethidium bromide (Fig. 1G,H)
Permacol has been used for years as a surgical implant, providing durability and strength for ventral hernia repair and abdominal wall reconstruction[30,31]

Summary

Introduction

Designed as a skin substitute, both epidermal and dermal acellular matrices (scaffolds) obtained after different decellularisation processes have been under investigation for over a decade[1,2,3,4,5]. Because of lower cellular infiltration, extracellular matrix deposition, and neovascularization observed with Permacol, its use as a dermal substitute for wound healing has been reduced[7]. Effective decellularisation methodology is dictated by factors such as cellular density, organization, clinical application and biologic properties of the extracellular matrix (ECM)[8]. Cell recruitment and the release of bioactive peptides by protease-mediated ECM degradation are thought to play a role in the constructive remodeling process and in wound healing[11]. Wound healing is a complex, dynamic, multicellular process that involves several overlapping stages including inflammation, formation of granulation tissue, re-epithelialization and remodeling[12].

Methods

Results

Conclusion