MicroSphere\n3D Structures Delay Tissue Senescence\nthrough Mechanotransduction

The\nextracellular matrix (ECM) stores signaling molecules and facilitates\nmechanical and biochemical signaling in cells. However, the influence\nof biomimetic “rejuvenation” ECM structures on aging-\nand degeneration-related cellular activities and tissue repair is\nnot well understood. We combined physical extrusion and precise “on–off”\nalternating cross-linking methods to create anisotropic biomaterial\nmicrogels (MicroRod and MicroSphere) and explored how they regulate\nthe cell activities of the nucleus pulposus (NP) and their potential\nantidegenerative effects on intervertebral discs. NP cells exhibited\naligned growth along the surface of the MicroRod, enhanced proliferation,\nand reduced apoptosis. This suggests an adaptive cellular response\ninvolving adhesion and mechanosensing, which causes cytoskeletal extension\nvia environmental cues. NP cells maintain nuclear membrane integrity\nthrough the YAP/TAZ pathway, which activates the cGAS-STING pathway\nto rectify the aging mechanisms. In vivo, MicroRod carries NP cells\nand reduces inflammatory factor and protease secretion in degenerated\nintervertebral discs, inhibiting degeneration and promoting NP tissue\nregeneration. Our findings highlight the role of mechanical stress\nin maintaining cellular activity and antiaging effects in harsh environments,\nproviding a foundation for further research and development of antidegenerative\nbiomaterials.