Nanoscale Zinc Substituted Hydroxyapatites: Potential Bone Grafting Biomaterials with Antibacterial Properties

Abstract

The need for antimicrobial bone graft substitutes capable of preventing and treating bone infections remains largely unmet by the currently available bone grafting materials. Clinical approaches in managing this disease typically rely on introducing antibiotics which—while effective—raise concerns about the issue of antimicrobial resistance. There is an opportunity to consider new approaches based on the development of antimicrobial bone graft substitute materials, and one promising approach is the development of nanoscale calcium phosphates with antimicrobial metal ions that possess antimicrobial properties while retaining good cytocompatibility. Zinc, known for its broad-spectrum antimicrobial activity and established role in bone regeneration, offers a promising candidate. Therefore, the aim of this research was to develop a novel injectable nanoscale hydroxyapatite incorporating zinc, designed to possess both antimicrobial effectiveness and cytocompatibility. Using modifications of the rapid mix wet precipitation method established in Sheffield, a series of nanoscale zinc substituted hydroxyapatite materials (ZnHA) were prepared by molar substitutions of calcium with zinc, using different zinc precursors. Materials characterisation results demonstrated the successful preparation of a range of nanoscale ZnHA (0 – 20 mol.%), especially effective when an alkaline pH was maintained. The antimicrobial activity was evaluated using clinically relevant gram-positive and gram-negative bacteria commonly associated with bone infections (methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli). The results indicated that the most promising materials were able to inhibit bacterial growth in suspension and prevent biofilm formation in a dose-dependent manner. Importantly, these materials also exhibited no cytotoxic effects in a direct in vitro cytocompatibility assay, reinforcing their potential for safe clinical application. In conclusion, this thesis reports the successful development and optimisation of nanoscale zinc substituted hydroxyapatites, representing a highly promising step toward the manufacture of effective antimicrobial bone grafts that could reduce infection-related complications and improve patient recovery outcomes globally.