Clinical Translation of Novel Bioceramics in Bone Regenerative Applications: Commercial Manufacturing Process Development and Preclinical Evaluation

Abstract

Novel bioceramics have been developed to address the unmet clinical need for a bone regenerative biomaterial that duplicates the performance of natural bone, achieving the critical combination of mechanical properties and bioactivity for bone regeneration in load-bearing applications. To create a compelling argument for clinical use, the performance of novel bioceramics materials, Sr-HT-Gahnite (SHG) and Baghdadite (BAG), must be established relative to clinically available bioceramic materials, hydroxyapatite (HA) and tricalcium phosphate (TCP). Additionally, to facilitate a smooth transition to commercial manufacture, an increased understanding of the effects of manufacturing process parameters, including particle size reduction, sintering, and sterilisation, on material performance is required, addressing the downfall of many commercialisation projects where promising research results cannot be replicated under commercial production controls.

The results show that the performance of SHG and BAG is superior to that of HA and TCP. While manufacturing inputs influence their properties, the superiority of SHG and BAG is demonstrated under commercially viable processes and with non-optimised parameters, therefore supporting continued progression to a regulatory approval process. The results highlight the need for strict equipment control, calibration, and maintenance during commercial manufacture, and the need to consider the required material performance for a given medical device application before changing manufacturing process parameters. The preclinical evaluation of SHG shows that the material properties are maintained when fabricated as a medical device, with SHG cervical fusion cages achieving spinal fusion without toxicity effects.

The findings in this thesis support the ongoing clinical translation of novel bioceramic materials, particularly SHG, with properties that address the need for a superior synthetic bone regenerative biomaterial.