A High-Density Hydrogen Bond Locking Strategy for Constructing Anisotropic High-Strength Hydrogel-Based Meniscus Substitute

Mimicking anisotropic features is crucial for developing artificial load-bearing soft tissues such as menisci). Here, a high-density hydrogen bond locking (HDHBL) strategy, involving preloading a poly(N-acryloylsemicarbazide) (PNASC) hydrogel with an aqueous solution containing a hydrogen bond breaking agent, followed by water exchange, to fabricate anisotropic high-strength hydrogels are proposed. During this process, multiple high-density hydrogen bonds of the PNASC network are re-established, firmly freezing oriented molecular chains, and creating a network with an anisotropic microstructure. The resulting anisotropic hydrogels exhibit superior mechanical properties: tensile strength over 9 MPa, Young's modulus exceeding 120 MPa along the orientation direction, and fatigue thresholds exceeding 1900 J m-2. These properties meet the mechanical demands for load-bearing tissue substitutes compared to other reported anti-fatigue hydrogels. This strategy enables the construction of an anisotropic meniscal scaffold composed of circumferentially oriented microfibers by preloading a digital light processing-3D printed PNASC hydrogel-based wedge-shaped construct with a resilient poly(N-acryloyl glycinamide) hydrogel. The 12-week implantation of a meniscus scaffold in rabbit knee joints after meniscectomy demonstrates a chondroprotective effect on the femoral condyle and tibial plateau, substantially ameliorating the progression of osteoarthritis. The HDHBL strategy enables the fabrication of various anisotropic polymer hydrogels, broadening their scope of application. A high-density hydrogen-bond locking strategy is proposed for customizing circumferentially anisotropic meniscal skeletons. It involves preloading digital light processing 3D-printed highly stiff gels, followed by water exchange to reconstruct multiple hydrogen bonds, freezing the molecular chains and anisotropic microstructures. Biomimetic meniscus scaffolds, fabricated by infilling the resilient hydrogel into a stiff skeleton, efficiently protect articular cartilage and alleviate osteoarthritis progression. image