Long-Term Natural Hydroxyapatite and Synthetic Collagen Hydroxyapatite Enhance Bone Regeneration and Implant Fixation Similar to Allograft in a Sheep Model of Implant Integration

There is an increasing demand for a suitable bone substitute to replace current clinical gold standard autografts or allografts. Majority of previous studies have focused on the early effects of substitutes on bone formation, while information on their long-term efficacies remains limited. This study investigated the efficacies of natural hydroxyapatite (nHA) derived from oyster shells and synthetic hydroxyapatite mixed with collagen (COL/HA) or chitosan (CS/HA) on bone regeneration and implant fixation in sheep. Titanium implants were inserted into critical-size defects in distal femur condyles bilaterally, and circumferential gaps around implants were filled with substitute materials or allografts (as control). 14 or 24 weeks post-operatively, the implant-bone blocks were harvested and evaluated using microarchitectural, histomorphometric, and mechanical methods. The nHA and COL/HA groups showed significant bone formation at both 14 and 24 weeks. There was a pronounced increase in bone tissue volume and ingrowth into titanium implant's porous surfaces, significantly enhancing mechanical fixation strength at 24 weeks. CS/HA had a limited ability to induce bone formation and implant fixation. We conclude that nHA and COL/HA revealed long-term effects on enhancing bone formation and implant fixation that were at least as good as allograft after 24 weeks, and both nHA and COL/HA appear to be good alternative materials to bone allograft.