Roles of Biomaterials in Cell-based Therapies for Disc Degeneration

Abstract

Degenerative disc disease poses an increasing threat to our quality of life as we age. Existing treatments have limitations. New treatment modalities using biological approaches are appealing. While cells including mesenchymal stem cells (MSC) are proving themselves potential candidates for treating disc degeneration, biomaterials are demonstrating their important roles in supporting and potentiating such therapies. During intradiscal injection, the vast majority of cells leaked out via back flow from the injection portal, reducing the efficacy of treatment. Recent evidence even suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, leading to an undesirable side-effect of MSC-based therapy. This suggests the significance of developing appropriate cell carriers and effective approaches to prevent leakage and associated osteophyte formation before MSC-based therapies can be applied in a clinical setting. Using a collagen microencapsulation platform, we fabricated collagen microspheres entrapping MSCs, supporting their survival, proliferation, differentiation and matrix remodeling. Using a rabbit disc degeneration model, we showed that, comparing with delivering MSC in saline, delivering MSC in collagen microspheres significantly reduced the risk of osteophyte formation. Using a photochemical crosslinking technology, we further fabricated an injectable collagen-based annulus plug to block the injection portal during intradiscal delivery. Ex vivo studies showed that the plug survived physiologically relevant loadings and significantly reduced leakage and enhanced retention of the injected materials. In vivo rabbit disc degeneration model showed that the plug significantly reduced osteophyte formation, suggesting the potential of the annulus plug as an adjunct or annulus closure device for intradisc delivery of cells and materials. Apart from facilitating cell delivery as shown in the above mentioned example, biomaterials play important roles in immobilizing soluble signals such as growth factors, providing structural and mechanical support to cells and tissues, presenting microenvironmental clues or niches, and acting as the template for functional remodeling of cells and tissues. Detailed discussion and examples on these functions of biomaterials will be given in this study. Disclosure of Interest None declared