Development of osteoinductive coatings for spinal implants (fusion cages)

When conservative treatment fails for more than two years, patients suffering from lower back pain might be subject to spine fusion surgery. The procedure’s high chances for post-operative complications explain why it is used as a last resort. If early integration of the fusion cage is achieved, the probability of postoperative complications is lowered. This thesis aimed to improve the osteointegration of spinal fusion cages by developing an osteoinductive coating based on sol-gel chemistry and composed of TiO2 and Mg and Sr-substituted hydroxyapatite (sHAP). To reduce variability during the project, the in vitro culture of mesenchymal stem cells (MSCs) in serum-free media (SFM) was studied. One commercially available SFM outperformed standard culture conditions and specialised media containing human serum. Changing media once a week was enough for immortalised MSCs to become confluent in 7 days and start showing signs of differentiation in 14 days when cultured in osteogenic media. Using design of experiments (DoE), the synthesis conditions of Mg and Sr sHAP were optimised, enhancing sHAP’s osteogenic potential. The best-performing formulation, synthesised with 10% Mg and 5% Sr substitutions, and 15 ml of ammonia for pH control, significantly increased alkaline phosphatase (ALP) activity in MSCs compared to commercially available sHAP. DoE was also used to improve the synthesis of TiO2 through sol-gel chemistry, allowing crystallisation at sintering temperatures sustainable by PEEK during the coating process. With optimal reaction temperature, sintering time, and the correct ratio between solvent, reagents, and peptising agent, TiO2 can reach up to 80% crystallinity when sintered at 250°C. Finally, this thesis found that a TiO2/HAP coating can increase the osteogenic potential of different substrates. Using DoE, the optimal coating conditions were found to include the deposition of 5 layers of a TiO2/sHAP composite, a short and fast dipping process, and a faster heating step during sintering.