Injectable gelatin/hyaluronic acid hydrogels incorporating oxidized alginate microparticles for controlled delivery of platelet-derived factors in cartilage regeneration

Osteoarthritis affects millions worldwide, yet current intra-articular treatments provide limited durability due to rapid therapeutics clearance and poor intrinsic cartilage repair capacity. We present an injectable, pore-forming hydrogel platform designed for controlled delivery of platelet-derived bioactive factors while promoting cell infiltration for cartilage regeneration. The system integrates functionalized gelatin and hyaluronic acid networks with oxidized alginate microparticles that act simultaneously as porogens and platelet lysate (PL) carriers, generating a dynamic microenvironment favorable for tissue repair. Microparticles produced via emulsification/internal gelation show tunable degradation governed by alginate oxidation, enabling programmable release kinetics. Hydrogels containing 10% (w/v) microparticles exhibited a compressive modulus of 37.7 kPa and photocrosslinked in under 60 s, supporting minimally invasive arthroscopic use. Release studies confirmed sustained protein delivery for up to 31 days, with oxidized microparticles (5% oxidation) releasing over 95% of encapsulated PL in correlation with their degradation, while blending with unmodified alginate offered further tunability. In chondrocyte-loaded constructs, PL-releasing hydrogels significantly enhanced proliferation and extracellular matrix deposition. Immunofluorescence showed increased aggrecan and collagen type-II, indicating preservation of chondrocyte phenotype and hyaline-like matrix formation. This dual-function injectable system couples localized trophic factor release with porosity-driven cell migration, offering a promising polysaccharide-centred strategy for clinically translatable cartilage repair.