Engineered dermal tissue constructs using mesenchymal stromal cells and TGF-β3-loaded electrospun dressings for stimulated wound healing process

Abstract

Transforming growth factor-beta 3 (TGF-β3) has been shown to promote wound healing by regulating key cellular processes. However, its clinical application is limited by the need for repeated dosing and by its labile nature, as TGF-β3 is sensitive to physiological fluctuations in temperature and pH, which can compromise its stability and efficacy. In this study, we developed a novel scaffold composed of poly(ε-caprolactone) and type I collagen as a matrix to immobilize calcium alginate capsules loaded with TGF-β3, called PCAT. This system enables localized delivery of the factor to the lesion site while preserving its bioactivity, positioning PCAT as an effective growth factor-release platform. In vitro characterization using human Wharton's jelly mesenchymal stromal cells (hWJ-MSCs) cultured on PCAT was conducted to assess cytocompatibility, bioactivity and growth factor quantification. Additionally, the tissue construct formed by hWJ-MSCs and PCAT was evaluated in vivo using full-thickness wound and epidermal skin grafts. The results demonstrated that PCAT preserved TGF-β3 - bioactivity, enabled sustained and localized delivery, promoted hWJ-MSCs proliferation, and modulated the secretion of growth factors associated with skin wound healing in vitro. Histological analysis showed that PCAT/hWJ-MSCs promoted epidermal skin grafts integration, evidenced by the presence of epidermal ridges (ER) and dermal papillae (DP). In addition, granulation tissue was characterized by thick and long collagen fibers, well-formed blood vessels (BV), and a low prevalence of inflammatory cells (IC). These results suggest that PCAT/hWJ-MSCs construct effectively stimulates wound healing and represents a promising strategy for skin tissue repair.