Multiscale mechanical-adapted hydrogels for the repair of intervertebral disc degeneration

Nucleus pulposus (NP) tissue engineering brings new hope in the repair of intervertebral disc degeneration (IVDD). IVDD is often accompanied by multiscale changes in the mechanical microenvironment, including the changes of mechanical property of collagen fibril, NP tissue, and mechanical instability of spine. In this study, a multiscale mechanically-adapted strategy is proposed to promote NP repair. To achieve this goal, a viscoelastic-adapted dual-network hydrogel (PVA-DN) is constructed. The hydrogel with multiscale tunable viscoelasticity and dynamic compression condition is used to meet the multiscale mechanical requirements of NP regeneration. The results show that the viscoelastic hydrogel promotes the proliferation, migration and adhesion of nucleus pulposus cell (NPC) as well as the secretion of NP-specific extracellular matrix. RNA-seq results show that it attenuates the inflammatory microenvironment by inhibiting the IL-17 signaling pathway. Appropriate dynamic compression applied to the viscoelastic scaffold further promotes the physiological function of NPC, and the viscoelasticity of hydrogel protects against NPC damage induced by excessive compression. Animal experiments demonstrate that the viscoelastic hydrogel effectively restores disc mechanical function and delays disc degeneration in rats. Findings from this study highlight that the multiscale mechanically-adapted strategy is effective in the repair of IVDD.