Human platelet lysates (hPL) have been explored in regenerative medicine as a source of growth factors and other bioactive proteins. However, their poor mechanical properties often fail to recapitulate hard tissues such as bone or bone-to-cartilage interfaces. To address this challenge, mechanically reinforced nanocomposite hydrogels were developed, by integrating functionalized nano-hydroxyapatite (nHAp-MA) within a bioactive organic matrix through a tailored interfacial strategy. This strategy enabled achieving an injectable hPL solution through ECD/NHS chemistry which could be later photocrosslinked in situ, taking advantage of the photocurable moieties of both the organic and inorganic components. Rheological data revealed an increase in the elastic modulus in two moments: the first after nHAp incorporation and the second after photocrosslinking. Enhanced mechanical properties were obtained in the functionalized nanocomposite materials when used at high concentrations. The increase in the particle content from 1 to 5 % highlighted the importance of particle functionalization to maintain mechanical stability. These nanocomposite hydrogels also presented controlled protein release over time, and great biological performance both in vitro and in vivo. By playing with the quantity of chemical crosslinker and nanoparticle content, tunable properties were achieved in tough and injectable human-based biomaterials, promising for a range of biomedical applications. STATEMENT OF SIGNIFICANCE: This study reports, for the first time, mechanically reinforced yet injectable hydrogels engineered from human blood-derived materials. While these materials enclose very interesting properties, being xeno-free, highly rich in growth factors and potentially from an autologous source, they lack robustness and mechanical stability for enduring continuous wearing. To achieve that, we developed a strategy to chemically bind nano-hydroxyapatite to protein matrices, enabling not only mimicking bone tissue composition, but also achieving injectable properties, rendering these biomaterials particularly promising for minimally invasive surgical applications. Moreover, our strategy demonstrated being tunable, supporting stem cells growth and promoting bone healing in vivo experiments. These advances bring us closer to patient-specific therapies using safer, more robust materials that avoid animal-derived products.
