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.