A gel microparticle-based self-thickening strategy for 3D printing high-modulus hydrogels skeleton cushioned with PNAGA hydrogel mimicking anisotropic mechanics of meniscus

Developing a meniscus substitute mimicking the anisotropic mechanics (higher circumferential tensile modulus and lower compressive modulus) of native tissue remains a great challenge. In this work, based on the pendant group structure-dependent H-bonding strengthening mechanism, two kinds of amide-based H-bonding crosslinked hydrogels with distinct mechanical behaviors, that is, the flexible poly(N-acryloyl glycinamide) (PNAGA) and the ultra-stiff poly(N-acryloylsemicarbazide) (PNASC) hydrogels are employed to construct the biomimetic meniscus substitute. To this end, a gel microparticle-based self-thickening strategy is first proposed to fabricate PNASC (GMP-PNASC) high-modulus hydrogels skeleton by extrusion printing technology in mimicking the collagen fibers in native meniscus to resist the circumferential tensile stress. Then, the PNAGA hydrogel is infused into the PNASC skeleton to replicate the proteoglycan, providing a lower compressive modulus. By regulating the structural features at the interior and peripheral regions, the GMP-PNASC/PNAGA hydrogel meniscus scaffold with the higher tensile modulus (87.28 ± 6.06 MPa) and lower compressive modulus (2.11 ± 0.28 MPa) can be constructed. In vivo outcome at 12 weeks post-implantation of rabbit's medial meniscectomy model confirms the effects of GMP-PNASC/PNAGA meniscus scaffold on alleviating the wear of articular cartilage and ameliorating the development of osteoarthritis (OA).