Generation of niche tuned antifibrotic fibroblasts and non-viral mediated endothelial commitment using adipose stem cells for dermal graft development.

Abstract

Cell-based skin substitute generation has seen considerable development. Combining synthetic scaffolds with biomimetic fibrin does direct both exogenous and endogenous stem cell differentiation, addressing needs for reliable tissue engineering. However, lack of immediate vasculature within implantable grafts remains critical for its sustenance and integration. Multipotency, high proliferation potential, ability to release multiple growth factors (GFs), and autologous availability highlight the use of human adipose derived mesenchymal stem cells (hADMSCs) in tissue-engineered dermal grafts (TEDG) construction. However, hADMSCs' insufficiency to independently establish angiogenesis within tissue constructs demands improvement of stem cell application for dermal graft survival. Approaches to harness microenvironmentally sensitive paracrine interactions could improve the angiogenic efficiency of hADMSCs within TEDG. This study conceptualized a fibrin-based niche, to direct hADMSCs toward a nonfibrotic fibroblast commitment and incorporation of bioengineered hADMSCs, specifically releasing potent angiogenic factors within TEDG. Coexistence of tuned fibroblast and endothelial lineage committed cells contributed to well-regulated extracellular matrix formation and prevascularization. Adequate cell proliferation; sustained transient release of angiogenic GFs till 20 days; directed dermal, endothelial, fibroblast, and vascular smooth muscle cell differentiation; and favored elastin and collagen deposition were achieved in vitro. In conclusion, specific niche composition and employment of bioengineered hADMSCs favor implantable TEDG construction.