A meticulous biocompatibility and toxicological assessment of a self-assembling peptide nanofiber-nanoceramic biomimetic nanocomposite, per ISO 10993 guidelines.

Abstract

Bone, a complex nanocomposite, has yet to be successfully replicated in a commercially available bone regenerative product that fully recapitulates this dual-phase nanoscale architecture. This study investigated the biocompatibility and safety of a nanoalloplastic composed of spherical nanohydroxyapatite (nHA; 30-45 nm)/tricalcium phosphate (TCP) and osteogenic, angiogenic and immunomodulatory self-assembling peptide nanofibers (15-20 nm), designed to mimic the natural nanocomposite structure of bone. Adhering to ISO 10993 protocols, the nanocomposite was subjected to rigorous biocompatibility evaluation by IFDA laboratories. This assessment encompassed cytotoxicity, genotoxicity, hemocompatibility, sensitization, and irritation, as well as acute and chronic systemic toxicity studies. Results demonstrated the material's non-cytotoxic nature, with no significant reduction in cell viability. Hemocompatibility testing revealed acceptable hemolytic activity, while genotoxicity assays showed no evidence of DNA damage. Neither irritation nor sensitization was observed. Systemic toxicity studies in mice revealed no adverse clinical signs, weight changes, or organ pathologies. Bone regeneration study showed complete and osteoinductive potential over one month in rabbits. The peptide nanofibers contribute to the material's biocompatibility through their ECM-mimicking sequences, nanofibrous architecture, biodegradability, and toxic- and solvent-free nature. TCP and spherical nHA with an optimum particle size, morphology, crystallinity, dissolution rate, and significant pH stability, collectively ensure its biocompatibility and vascularized bone formation. These findings validate the biocompatibility and safety of this osteoinductive nanocomposite. The integration of spherical nHA and self-assembling peptide nanofibers appears to generate a biomimetic microenvironment that improves cellular interactions, thereby accelerating bone regeneration and confirming its biocompatibility, positioning it as a revolutionary solution for bone regeneration.