Fabrication of nanoparticles for bone regeneration: new insight into applications of nanoemulsion technology

Abstract

Introducing synthetic bone substitutes into the clinic was a major breakthrough in the regenerative medicine of bone. Despite many advantages of currently available bone implant materials such as biocompatiblity and osteoconductivity, they still suffer from relatively poor bioactivity, osteoinductivity and osteointegration. These properties can be effectively enhanced by functionalization of implant materials with nanoparticles such as osteoinductive hydroxyapatite nanocrystals, resembling inorganic part of the bone, or bioactive polymer nanoparticles providing sustained delivery of pro-osteogenic agents directly at implantation site. One of the most widespread techniques for fabrication of nanoparticles for bone regeneration applications is nanoemulsification. It allows manufacturing of nanoscale particles (<100 nm) that are injectable, 3D-printable, offer high surface-area-to-volume-ratio and minimal mass transport limitations. Nanoparticles obtained by this technique are of particular interest for biomedical engineering due to fabrication procedures requiring low surfactant concentrations, which translates into reduced risk of surfactant-relatedin vivoadverse effects and improved biocompatibility of the product. This review discusses nanoemulsion technology and its current uses in manufacturing of nanoparticles for bone regeneration applications. In the first section, we introduce basic concepts of nanoemulsification including nanoemulsion formation, properties and preparation methods. In the next sections, we focus on applications of nanoemulsions in fabrication of nanoparticles used for delivery of drugs/biomolecules facilitating osteogenesis and functionalization of bone implants with special emphasis on biomimetic hydroxyapatite nanoparticles, synthetic polymer nanoparticles loaded with bioactive compounds and bone-targeting nanoparticles. We also highlight key challenges in formulation of nanoparticlesviananoemulsification and outline potential further improvements in this field.