Highly Mechanically Robust Human-Derived Hydrogels for Tissue Engineering Applications

Hydrogels are widely used in tissue engineering (TE) for their ability to replicate the extracellular matrix, providing a supportive environment for cell proliferation and tissue regeneration. However, their inherently low mechanical strength often restricts their use in load-bearing biomedical applications. To address these limitations, this study aimed to develop the first human-derived double-network (DN) hydrogel by combining human methacryloyl platelet lysates (hPLMA) and the natural polysaccharide chitosan (CHT) through sequential covalent and ionic crosslinking. The resulting DN hydrogel was mechanically and biologically characterized to evaluate its suitability for TE applications. Remarkably, the hPLMA/CHT DN hydrogels exhibit outstanding compressive strength of 1.3 ± 0.13 MPa and 86% hysteresis recovery after 10 loading cycles at 70% strain, underscoring their mechanical resilience. Moreover, the DN hydrogels were able to maintain enhanced cell viability, adhesion, and proliferation following the three-dimensional encapsulation of human adipose-derived stem cells. This unique formulation achieves an excellent balance between mechanical robustness and biocompatibility. By integrating mechanical resilience with human-derived bioactivity, hPLMA-based DN hydrogels offer a superior alternative to synthetic systems for cartilage or musculoskeletal regeneration. Overall, the combination of high mechanical strength, fatigue resistance, and cytocompatibility highlights the potential of hPLMA/CHT DN hydrogels as a promising platform for load-bearing and mechanically demanding TE applications.