Redefining Fascia: A Mechanobiological Hub and Stem Cell Reservoir in Regeneration-A Systematic Review.

Fascia, once considered a passive connective covering, is now recognized as a mechanosensitive tissue and stem cell niche with roles in regeneration, ECM remodeling, and immune-vascular regulation. The aim of this review was to synthetize evidence of fascia-derived progenitors and their mechanobiological functions across in vitro, preclinical and clinical domains. A systematic search of PubMed, Scopus and Web of Science (up to August 2025) was performed in accordance with PRIMS guidelines. Eligible studies addressed fascia in relation to stem/progenitor cells and regenerative outcomes. Risk of bias was assessed with OHAT criteria for in vitro studies, SYRCLE for animal studies and ROBINS-I for clinical studies. Of 648 records identified, 34 studies were included, encompassing 17 in vitro, 17 animal and 4 clinical investigations, with overlap across domains, and 3 reviews. In vitro, fascia-derived stem cells (FDSCs), FAPs and ASCs were shown to remodel ECM, promote angiogenesis and respond to mechanical cues. Animal models revealed collective fibroblast migration as ECM patches, regulated by N-cadherin, Connexin43 and p120-catenin, while CD201+ progenitors directed scar formation. Clinical studies, though few, reported improved outcomes with subfascial PRP injections and adipofascial flaps. Fascia appears as an active mechanobiological hub and stem cell reservoir that may influence tissue repair and fibrosis, although current evidence, particularly from clinical studies, remains preliminary. Despite promising insights, evidence is limited by methodological heterogeneity, emphasizing the need for mechanistic human studies and well-powered clinical trials.