Abstract

Intervertebral disc degeneration (IDD) is the pathological basis of disc degenerative diseases (DDD). Reduction in the number of cells and degeneration of the extracellular matrix (ECM) in the nucleus pulposus (NP) are characteristics of IDD. Bio-hydrogel combined with stem cell transplantation is a promising treatment. Injectable ECM hydrogels have good biological activity and in-situ gelatinization. However, its biomechanics and stability are insufficient to provide adequate mechanical support for intervertebral discs and to maintain the long-term differential stimulus for seeded stem cells. In our study, we developed genipin cross-linked decellularized nucleus pulposus hydrogel (GDH) as delivery system. We evaluated the mechanical properties, stability, biocompatibility, and differentiation induction of GDH cross-linked with different concentrations of genipin in vitro. The GDH-loaded adipose-derived mesenchymal stem cells (ADSCs) (GDHA) were injected into the rat degenerated coccygeal intervertebral disc. The effect of intervertebral disc regeneration in vivo was evaluated. The results showed that GDH with 0.02% of genipin had similar elastic modulus to human nucleus pulposus, good biocompatibility, and inducibility of expressing NP-related genes. In vivo studies showed that GDHA improved the survival of ADSCs and improved the intervertebral height, MRI index, and histological grading score. In conclusion, GDH, as an outstanding bio-hydrogel cell delivery system, has the therapeutic potential for retarding IDD.

Highlights

  • It is reported that low-back pain is currently the second leading cause of hospitalization and disability for elders, placing a serious financial burden on individuals and society (Cieza et al, 2021)

  • We demonstrated that this adipose-derived mesenchymal stem cells (ADSCs)–genipin-decellularized nucleus pulposus hydrogel (DNPH) complex could retard Intervertebral disc degeneration (IDD) significantly

  • We developed a novel genipin crosslinked decellularized nucleus pulposus (NP) hydrogel-like cell delivery system to deliver ADSCs into Intervertebral discs (IVDs)

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Summary

Introduction

It is reported that low-back pain is currently the second leading cause of hospitalization and disability for elders, placing a serious financial burden on individuals and society (Cieza et al, 2021). Intervertebral disc degeneration (IDD) is the primary pathological basis of low-back pain. Intervertebral discs (IVDs) are composed of a central. GDHA Retards Intervertebral Disc Degeneration nucleus pulposus (NP), surrounded by the annulus fibrosus and cartilaginous endplates (Eyring, 1969). Current clinical treatments for IDD-caused low-back pain include medication intervention, surgical depression, and fusion. Both of them cannot reverse the pathological process of IDD. There is an urgent need for a satisfactory solution to reengineer the natural properties of IVD (Benneker et al, 2014)

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