An Injectable Engineered Cartilage Gel Improves Intervertebral Disc Repair in a Rat Nucleotomy Model

Abstract

Abstract Background: Lower back pain is a major problem caused by intervertebral disc degeneration, resulting in a significant burden on individuals and society. A common surgical procedure is lumbar partial discectomy (excision of the herniated disc causing nerve root compression) results in further disc degeneration, leading to severe lower back pain and disability after discectomy. Thus, the development of disc regenerative therapies for patients who require lumbar partial discectomy is crucial. This study aimed to restore the intervertebral disc structure and functions by utilizing injectable engineered cartilage gel. Methods: We investigated the effectiveness of an engineered cartilage gel utilizing human fetal cartilage-derived progenitor cells (hFCPCs) on intervertebral disc repair in a rat tail nucleotomy model. Eight-week-old female Sprague-Dawley rats were randomized into three groups to undergo intradiscal injection of (1) cartilage gel, (2) hFCPCs, or (3) decellularized extracellular matrix (ECM) (n=10/each group). The treatment materials were injected immediately after nucleotomy of the coccygeal discs. The coccygeal discs were removed 6 weeks after implantation for radiologic and histological analysis. Results: Implantation of the cartilage gel promoted degenerative disc repair compared to hFCPCs or hFCPC-derived ECM by increasing the cellularity and matrix integrity, promoting reconstruction of the nucleus pulposus, restoring disc hydration, and downregulating inflammatory cytokines and pain. Conclusions: Our results demonstrate that injectable engineered cartilage gel has higher therapeutic potential than its cellular or ECM component alone, and support further translation to large animal models and human subjects. In the future, simple intradiscal injections of injectable engineered cartilage gel may be an effective treatment option without any scaffolds or growth factors for intervertebral disc degeneration diseases.