Tissue engineering strategies in spinal arthrodesis: the development of new models with the potential to promote fusion

Abstract

Skeletal disorders requiring the regeneration or de novo production of bone present considerable reconstructive challenges and are one of the main driving forces for the development of skeletal tissue engineering strategies today. The incorporation of stem cell technology with material science has been pivotal in the design and application of tissue engineering strategies for bone regeneration but requires a detailed understanding of the complex interactions that occur between stem cells, osteoinductive stimuli, osteoconductive constructs and the biomechanical environment. The requirement for tissue engineering strategies in spinal arthrodesis highlights just one example of the clinical imperative for such strategies. Being a field of personal clinical interest, recent tissue engineering strategies employed to promote spinal fusion and the ongoing challenges to successful clinical translation, are considered in greater detail for the purposes of this thesis. The work in this thesis explores the role of two novel tissue engineering strategies to promote bone tissue regeneration and considers the potential application of these strategies for spinal arthrodesis. Firstly, by examining in vitro and ex vivo the effect of a titanium-spray coated nanopatterned surface on skeletal stem cell behaviour and embryonic chick femur development, it attempts to identify whether nanotopography can direct skeletal stem cell differentiation along an osteoblastic lineage in the absence of chemical stimulation, and considers whether the arrangement of nanopits on the substrate surface affects the osteoinductive surface potential. Furthermore, attempts are made to develop a suitable animal model to analyse the effect of nanopatterned titanium-spray coated substrates in vivo. Secondly, by way of an in vitro study, this thesis analyses the effect of varying pore size on the osteoconductive potential of a 3-D printed 100% sintered hydroxyapatite scaffold seeded with skeletal stem cells. This thesis demonstrates the potential that nanotopography and 3-D printed scaffolds offer to tissue engineering strategiesfor skeletal regeneration but also highlights the challenges to clinical translation and the need for a collaborative multidisciplinary approach for future success.

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ORCID for Richard Oreffo: orcid.org/0000-0001-5995-6726

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