Nanohydroxyapatite and liposomes-coated integral bilayer scaffold for osteochondral repair via mimicking the dual differentiation microenvironment of BMSCs

Osteochondral defects pose an enormous challenge, and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone. Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect. Herein, a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed, involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation. This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and pro-osteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells. The fabricated composites were evaluated for mechanical, physicochemical, biological properties, in vitro and in vivo tissue regeneration potential. Overall, the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological, radiological and histological evaluation, verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.