Biodegradable FeMn bone graft substitutes : ‘in vitro’ and ‘in vivo’ testing

Abstract

Metallic biodegradable bone graft substitutes are still in the early stages of development. Nonetheless, they promise to provide a solution to taxing orthopaedic scenarios involving bone loss. To this end, they must be able to balance corrosion rate, cytotoxicity and structural support. Once in vivo, the ideal implant must be able to provide mechanical support in loadbearing orthopaedic scenarios, whilst also allowing newly-forming bone to replace it. Biodegradable Fe-based alloys are currently under study in this respect as they provide desirable structural characteristics. However as yet, the ideal balance between corrosion rate and cytotoxicity has not been established. In this project, pure Fe, Fe35Mn, Fe35Mn1Ag and Fe35Mn5Ag alloysin both as-ground and pre-corroded states were tested for in vitro cytotoxicity using direct contact techniques. They were found to cause significant cytotoxicity to two bone cell lines with no viable hFOB (asground) or MC3T3-E1 (pre-corroded) cells remaining after a four-day test period. In vivo experimentation on rats was also performed using Fe35Mn, Fe35Mn1Ag and Fe35Mn5Ag with no cytotoxic effects having been observed throughout a six-month implantation period. All of the implants were well-incorporated into surrounding bone and subsequent histological examination revealed well-formed bone matrix. The only difference between native bone and the newly-formed bone matrix was a black discolouration of the newly-formed bone, likely due to the presence of Mn corrosion products. While favourable biocompatibility results were obtained, the implants only exhibited very minimal corrosion throughout the six-month implantation period. It is likely that the slow corrosion may have contributed to these materials’ biocompatibility, suggesting that longer periods of precorrosion in vitro may yield more favourable cytotoxicity results. This work demonstrates the inherently cytotoxic nature of Fe alloys. Future work and development will need to focus on accelerating their rate of corrosion while maintaining their structural qualities. All the while, this must be done without increasing their cytotoxicity.