Nanohydroxyapatite composites' toxicity and biosafety for safe clinical translation

Nanohydroxyapatite (nHAp) is a promising biomaterial due to its structural similarity with the mineral phase of natural bone, high bioactivity, and broad applications in biomedical fields. Although this field is growing rapidly, there is no dedicated review which systematically offers an overview on toxicity and bio-safety profile of nHAp composites. The researchers reported that till 50-100 µg mL^-1 concentration of nHAp, cell viability was 80-90%, but as the concentration reached around 100-200 µg mL^-1, it caused oxidative stress, inflammation, decreased cell proliferation and mitochondrial dysfunction. This review aims to give a comparative critical summary of the toxicity aspects of nanohydroxyapatite composites, focusing on cytotoxicity, oxidative stress, genotoxicity and immunological responses. A particular focus is given to dose-dependent behaviour, ion-doping effects, and the effect of the various composite matrices on cellular responses. In addition, the potential toxicity differences between biomedical applications like bone regeneration, drug delivery systems and implant coatings are discussed. The review emphasizes the importance of in vivo studies, long-term toxicity testing, and standardized testing protocols for the safe clinical application of nHAp-based composites. In summary, nanohydroxyapatite composites hold great promise for advanced biomedical applications; nonetheless, their toxicity profile is complex and context-dependent, necessitating a sophisticated comprehension of their safety issues and therapeutic advantages.