Smart Platforms for Osteochondral Regeneration through on-demand Activation

Objective

Osteochondral (OC) defects, involving both articular cartilage and subchondral bone, are precursors of osteoarthritis (OA), a degenerative disease affecting >600 million people and expected to rise by 75% by 2050. Current treatments (pharmacological approaches, viscosupplementation, cell injections, acellular implants, surgery) are unsatisfactory, offering only temporary relief, poor-quality fibrocartilage, or lacking long-term integration. Total joint replacement, though effective, is invasive and risky, stressing the need for regenerative strategies able to restore the OC unit durably. SPORA addresses the poor bioactivity and limited clinical translation of current OC Tissue Engineering strategies by developing next-generation smart platforms based on stimuli-responsive biomaterials (hydrogels and nanocarriers) externally triggered by electric and magnetic stimulation. These platforms will enable spatiotemporal control of growth factor (GF) release, regulation of cell fate toward tissue-specific differentiation, and guidance of extracellular matrix deposition directly in situ. The project will progress through four main steps: (i) defining biomaterials, requirements, and regulatory frameworks using Artificial Intelligence (AI) tools; (ii) developing stimuli-responsive biomaterials and biofabricating the OC unit; (iii) optimizing external stimulation to modulate GF release; and (iv) validating the OC unit in vitro to assess human stem cell differentiation and tissue-specific matrix production. Clinically, SPORA aims to restore OC lesions and delay or prevent OA progression, but, beyond this impactful goal, the paradigm developed in SPORA can be readily adapted to other tissues and diseases (e.g., cardiac, wound, and muscle repair) by modulating the specific bioactive factors and optimizing their stimulus-driven delivery, thus opening the path toward a new era of adaptive regenerative biomaterials.