Cartilage‐Adaptive Hydrogels via the Synergy Strategy of Protein Templating and Mechanical Training

Abstract Cartilage, as a load‐bearing tissue with high‐water content, exhibits excellent elasticity and high strength. However, it is still a grand challenge to develop cartilage‐adaptive biomaterials for replacement or regeneration of damaged cartilage tissue. Herein, protein templating and mechanical training is integrated to fabricate crystal‐mediated oriented chitosan nanofibrillar hydrogels (O‐CN gels) with similar mechanical properties and water content of cartilage. The O‐CN gels with an ≈74 wt% water content exhibit high tensile strength (≈15.4 MPa) and Young's modulus (≈24.1 MPa), as well as excellent biocompatibility, antiswelling properties, and antibacterial capabilities. When implanted in the box defect of rat's tails, the O‐CN gels seal the cartilage (annulus fibrosus) defect, maintain the intervertebral disc height and finally prevent the nucleus herniation. This synergy strategy of protein templating and mechanical training opens up a new possibility to design highly mechanical hydrogels, especially for the replacement and regeneration of load‐bearing tissues.