Development and Analysis of Apatite-Mullite Glass-Ceramic Scaffolds; Towards Tissue Engineering of the Vertebral Endplate

Calcification of the vertebral endplate (EP) is a key factor relating to the onset of degenerative disc disease, a primary influencer of lower back pain which carries substantial social and economic burden. The aim of the current project was to investigate the feasibility of using apatite-mullite glass ceramic (AM-GC) to provide a bioactive scaffold for tissue engineering applications in the region of the vertebral EP. Consequently this material was fully characterised with regard to the natural tissues from a number of functional perspectives, mechanical, compositional, biological and those factors relating to the in vivo mass transfer of nutrients. Scaffolds were manufactured via a novel particle sintering approach to provide a range of porous substrates. Insight into the potential for tissue engineering the complex structures of the EP were provided using primary human mesenchymal stem/stromal cells (MSCs) due to their capacity to differentiate into both the osteogenic and chondrogenic lineages that constitute the natural EP structure. The results identified a novel heating regime able to produce AM-GC scaffolds mechanically suitable for EP application displaying mean pore size characteristics able to promote osteointergration with natural bone. Though identified as a bulk nucleating system substantial influence on surface composition was attributed to particle size fractions, with the 45-90 µm range deemed most suitable for bone applications. The differentiation capacity of MSCs on scaffolds utilising this particle size range exhibited excellent in vitro biocompatibility characteristics. Demonstrating a clear osteoconductive capacity along with the ability to support chondrogenic micro-mass culture, inferring potential for future development of in vitro AM-GC based EP constructs. To facilitate this future goal a permeability testing methodology was developed to replicate the in vivo nutrient mass transfer environment of the natural tissue. Initial testing proved this system fit for purpose allowing future in vitro engineered constructs to be comparatively analysed against natural EP mass transfer characteristics. Ensuring that future tissue engineering efforts in the region of the vertebral EP provide the necessary nutrient supply functionality essential for successful clinical application.