Natural bone-mimicking nanopore-incorporated hydroxyapatite scaffolds for enhanced bone tissue regeneration

Background: A considerable number of studies has been carried out to develop alloplastic bone graft materials such as hydroxyapatite (HAP) that mimic the hierarchical structure of natural bones with multiple levels of pores: macro-, micro-, and nanopores. Although nanopores are known to play many essential roles in natural bones, only a few studies have focused on HAPs containing them; none of those studies investigated the functions of nanopores in biological systems. Method: We developed a simple yet powerful method to introduce nanopores into alloplastic HAP bone graft materials in large quantities by simply pressing HAP nanoparticles and sintering them at a low temperature. Results: The size of nanopores in HAP scaffolds can be controlled between 16.5 and 30.2 nm by changing the sintering temperature. When nanopores with a size of ~ 30.2 nm, similar to that of nanopores in natural bones, are introduced into HAP scaffolds, the mechanical strength and cell proliferation and differentiation rates are significantly increased. The developed HAP scaffolds containing nanopores (SNPs) are biocompatible, with negligible erythema and inflammatory reactions. In addition, they enhance the bone regeneration when are implanted into a rabbit model. Furthermore, the bone regeneration efficiency of the HAP-based SNP is better than that of a commercially available bone graft material. Conclusion: Nanopores of HAP scaffolds are very important for improving the bone regeneration efficiency and may be one of the key factors to consider in designing highly efficient next-generation alloplastic bone graft materials.