Fibroblast-derived BMP5 promotes tendon adhesion by inducing bone marrow mesenchymal stromal cells to differentiate...

Tendon adhesion following injury remains a major clinical challenge, primarily driven by excessive fibrosis and aberrant cellular differentiation. Here, we identify fibroblast-derived bone morphogenetic protein 5 (BMP5) as a key paracrine signal that promotes mesenchymal stromal cell (MSC) differentiation into myofibroblasts, thereby exacerbating adhesion formation. Mechanistically, we show that paclitaxel (PTX) suppresses BMP5 expression in fibroblasts via inhibition of the HIF-1α pathway, thus blocking MSC-to-myofibroblast transition. To achieve sustained local delivery, we developed polylactic acid based membranes (PLA) incorporating PTX in either a blended (PLB) or conjugated (PLC) form, with PLC demonstrating controlled release, reduced cytotoxicity, and superior anti-adhesion efficacy. Collectively, our results reveal a BMP5-centered fibroblast-MSC axis as a key driver of tendon adhesion and establish PTX-loaded PLC membranes as a mechanism-based therapeutic strategy.