# Hepatocyte growth factor in biosheets promotes autonomous regeneration of cutaneous tissue after transplantation onto a full-thickness skin defect

## TL;DR

Biosheets containing hepatocyte growth factor (HGF) help regenerate skin tissue more effectively than fascia in mice.

## Contribution

The study identifies HGF as a key mediator in biosheet-induced skin regeneration through re-epithelialization and angiogenesis.

## Key findings

- Biosheets promote faster skin epithelialization compared to subcutaneous fascia in mouse models.
- HGF levels are significantly higher in biosheets and are essential for wound healing.
- Blocking HGF in biosheets impairs skin regeneration, confirming its role in the process.

## Abstract

Biosheets and biotubes are collagenous connective tissue membranes that surround unabsorbable molds embedded in living tissues, and can regenerate damaged tissues in various organs following in-situ transplantation. However, the mechanisms underlying tissue regeneration are still unclear. In this study, we analyzed the histological features and cellular composition in the biosheets, and observed dramatic time-dependent changes. We transplanted biosheets into full-thickness wounds in a mouse model, and evaluated skin regeneration through histological analysis in comparison with subcutaneous fascia transplantation. Our findings confirm that biosheets can accelerate epithelialization of skin wounds of mouse more effectively than fascia. To elucidate the mechanism underlying skin regeneration by biosheets, we compared the protein expression in the biosheets and subcutaneous fascia. Proteomics analysis revealed significant differences in the protein profiles of the biosheets and fascia, with marked elevation of hepatocyte growth factor (HGF) in the biosheets. Addition of HGF in situ accelerated angiogenesis and epithelial regeneration in the fascia-transplanted full-thickness wounds in mice. On the other hand, neutralization of HGF impaired the wound healing process following biosheet transplantation. In conclusion, our findings suggest that HGF mediates biosheet-mediated regeneration of cutaneous tissues by contributing to re-epithelialization and angiogenesis.

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•Biosheets have been investigated as scaffolds for cutaneous tissue regeneration.•Biosheets accelerated cutaneous regeneration in a mouse model.•Proteomic analysis of biosheets showed elevation of HGF, PDGF-β, TGF-β, and Cdk1.•Neutralization of HGF in biosheets by anti-HGF antibodies impaired cutaneous regeneration.

Biosheets have been investigated as scaffolds for cutaneous tissue regeneration.

Biosheets accelerated cutaneous regeneration in a mouse model.

Proteomic analysis of biosheets showed elevation of HGF, PDGF-β, TGF-β, and Cdk1.

Neutralization of HGF in biosheets by anti-HGF antibodies impaired cutaneous regeneration.