Potential of Notochordal Cells within Injectable Biomaterials to Promote Intervertebral Disc Regeneration

Abstract

Low back pain is the leading cause of disability worldwide and is strongly associated with degeneration of the intervertebral disc (IVD).During degeneration the nucleus pulposus (NP) in the core of the IVD, is affected by altered matrix synthesis, increased degradation, andcell loss. Strategies combining regenerative cell sources with injectable biomaterials could provide a therapeutic approach to treatingIVD-degeneration related back pain. The juvenile cells of the NP, known as notochordal cells (NC), could provide both anabolic andanti-catabolic responses for disc regeneration. However, their behaviour within biomaterial delivery systems has not been investigated.Here, porcine NCs were incorporated into three injectable hydrogels: Albugel (an albumin/hyaluronan hydrogel), NPgel (a L-pNIPAMco-DMAc hydrogel) and NPgel with decellularized NC-matrix powder (dNCM). The NCs and biomaterial constructs were cultured for upto 4 weeks under 5% oxygen (n = 3 biological repeats). The ability of biomaterials to maintain NC viability, phenotype and extracellularmatrix synthesis and deposition was investigated through histological, immunohisto chemical and glycosaminogly cans analysis. NCs survived in all three biomaterials after 4 weeks, whilst phenotype and cell clustering were maintained to a greater extent in NPgel and Albugel. Thus, these biomaterials could facilitate maintenance of the NC phenotype, support matrix deposition and be a basis for future IVD regeneration strategies.