Engineering a placenta-inspired biomimicking fibrous patch for chondrogenesis through immunomodulation

The frequent onset of hyper-inflammatory responses after implantation impairs the availability of tissue transplants, impedes cellular renewal, and ultimately leads to the failure of scaffold-based cartilage regeneration. Existing scaffold modification strategies show limited efficacy in controlling immune cell infiltration and modulating inflammatory responses. Inspired by the placenta's dual protective and immunomodulatory attributes—through its physical barrier and biofactors release—this study develops a biomimetic surface-engineered aligned poly (L-lactic acid) (PLLA) fibrous patch barrier with pH-responsive drug release capabilities to shield implanted grafts, control post-implantation immunomodulatory processes, and foster chondrogenesis. Results confirm the successful loading of the immunomodulatory biomolecule, hesperetin (Hes), onto the aligned fibrous patch via engineered polydopamine (PDA) coating. Leveraging the pH-responsive properties of PDA, this functional patch (Hes@PDA-PLLA) expedites Hes release by disrupting π-π interactions and hydrogen bonds in acidic environments compared to release in neutral conditions, thus achieving an inflammation-responsive Hes release. In vitro experiments corroborate the immunomodulatory capacity of the biomimetic patch, such as inducing macrophage phenotypic transition from pro-inflammatory to anti-inflammatory states and eliciting positive immunomodulatory effects on chondrocytes. Subsequent proof-of-concept experiments conducted subcutaneously in nude mice and rabbits validate the immunomodulatory barrier properties of Hes@PDA-PLLA to cell-laden fiber sheet and tissue-engineered cartilage block, diminishing immunological rejection, inhibiting fibrous sac formation, and fostering favorable cartilage remodeling. Overall, the biomimetic patch represents an engineered immune-responsive protective system designed to preclude host immune rejection post-implantation of biomaterials, offering a novel strategy for enhancing the transplantation viability of allogeneic cartilage tissues or other cell-involved implants.