Simultaneous targeting of TGF-β1/PD-L1 via a hydrogel-nanoparticle system to remodel the ECM and immune microenvironment for limiting adhesion formation

Adhesion seriously affects the recovery of tendon gliding function. Our group previously found that inhibition of TGF-β1, which is closely related to adhesion formation, effectively attenuated adhesions but did not eliminate them, suggesting that there may be other mechanisms involved in adhesion formation. In this study, we considered that uncontrolled and excessively proliferating fibroblasts undergo immune escape, which aggravates the deposition of extracellular matrix during the adhesion formation. We found that the expression of the immune checkpoint PD-L1 was significantly elevated after injury and may be involved in adhesion formation. Therefore, we intended to silence both TGF-β1 and PD-L1 to improve the immune advantage in the microenvironment after flexor tendon injury to further reduce adhesion. We constructed the nanoparticle/TGF-β1 or/and PD-L1 siRNA complexes and verified their high biocompatibility and high transfection efficiency. We found that CD8