Viscoelastic Hydrogel Promotes Disc Mechanical Homeostasis Repair and Delays Intervertebral Disc Degeneration via the Yes-Associated Protein Pathway.

Abstract

Intervertebral disc degeneration (IDD) process is accompanied by overactive inflammation and mechanical instability of the nucleus pulposus (NP). Current treatments do not fully restore the biomechanical environment of discs, limiting their therapeutic efficacy. Thus, novel strategies are required to combat IDD. Hydrogels have outstanding biocompatibility and mechanical properties, most importantly, absorbing and retaining water similar to human NP tissue, showing a unique superiority in the treatment of IDD. In this study, we employed a viscoelastic ionic hydrogel (VIG) composed of polyvinyl alcohol and magnesium ions to investigate the therapeutic effect for IDD. VIG demonstrated an optimal degradation rate and NP-biomimetic swelling behavior in vitro. In the rat model of IDD, VIG-injected discs demonstrated mechanical properties approximating those of native discs, including stiffness, relaxation, and dissipation capacity. Furthermore, finite element analysis demonstrated that VIG improved biomechanical function of degenerated discs. VIG effectively inhibited the progression of IDD in the rat model by increasing extracellular matrix synthesis and decreasing matrix metalloproteinase-13 (MMP-13) expression. Moreover, VIG promoted proliferation and differentiation of NP cells in response to extracellular mechanical changes through the integrin-YAP signaling pathway. These findings suggest that VIG has the potential to modulate the NP inflammatory microenvironment and restore mechanical stability in IDD. This work represents a straightforward and promising strategy for IDD treatment.