Antimicrobial hydroxyapatite and its composites for the repair of infected femoral condyle

Abstract

Orthopedic implant-associated infection constitutes one of the most devastating and challenging symptoms in the clinic. Implants without antimicrobial properties may become the harbourage for microbial colonization and biofilm formation, thus hindering normal bone regeneration processes. We had previously developed tannin modified HA (THA) as well as silver and tannin modified hydroxyapatite (HA) (Ag-THA) via a facile one-step and scalable process, and proven their antimicrobial performance in vitro. Herein, by compositing with nonantimicrobial polyurethane (PU), the in vivo anti-bacterial activity, osteoconductivity and osteoinductivity of PU/Ag-THA composite were investigated using an infected femoral condyle defect model on rat. PU/Ag-THA exhibited excellent in vivo antimicrobial activity, with the calculated bacteria fraction being reduced to lower than 3% at week 12 post operation. Meanwhile, PU/Ag-THA is also promising for bone regeneration under the bacteria challenge, evidenced by a final bone mineral density (BMD) similar to 0.6 times higher than that of the blank control at week 12. A continuous increase in BMD over time was observed in the PU/Ag-THA group, but not in the blank control and its non- or weak-antimicrobial counterparts (PU/HA and PU/THA), in which the growth rate of BMD declined after 8 weeks of operation. The enhanced osteoinductivity of PU/Ag-THA relative to blank control, PU/HA and PU/THA was also confirmed by the Runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) immunohistochemical staining. The above findings suggest that antimicrobial Ag-THA may serve as a promising and easy-to-produce antimicrobial mineral for the development of antimicrobial orthopedic composite implants to address the challenges in orthopedic surgeries, especially where infection may become a challenging condition to treat.