Development and biological evaluation of fluorophosphonate-modified hydroxyapatite for orthopaedic applications

There is an incentive to functionalise hydroxyapatite (HA) for orthopaedic implant use with bioactive agents to encourage superior integration of the implants into host bone. One such agent is (3S) 1-fluoro-3-hydroxy-4-(oleoyloxy) butyl- 1-phosphonate (FHBP), a phosphatase-resistant lysophosphatidic acid (LPA) analogue. We investigated the effect of an FHBP-HA coating on the maturation of human (MG63) osteoblast-like cells. Optimal coating conditions were identified and cell maturation on modified and unmodified, control HA surfaces was assessed. Stress tests were performed to evaluate coating survivorship after exposure to mechanical and thermal insults that are routinely encountered in the clinical environment. MG63 maturation was found to be 3 times greater on FHBP-modified HA compared to controls (p <0.0001). There was no significant loss of coating bioactivity after autoclaving (P= 0.9813) although functionality declined by 67% after mechanical cleaning and reuse (p<0.0001). The bioactivity of modified disks was significantly greater than that of controls following storage for up to 6 months (p<0.001). Herein we demonstrate that HA can be functionalised with FHBP in a facile, scalable manner and that this novel surface has the capacity to enhance osteoblast maturation. Improving the biological performance of HA in a bone regenerative setting could be realised through the simple conjugation of bioactive LPA species in the future.