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-related in vivo adverse 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 nanoparticles via nanoemulsification and outline potential further improvements in this field.
Highlights
Introducing synthetic bone substitutes into the clinic was a major breakthrough in the regenerative medicine of bone.[1]Barbara Kupikowska-Stobba, received her MSc degree in biotechnology from Warsaw University of Life Sciences (Poland) and PhD degree in biomedical engineering from Nalecz Institute of Biocybernetics and Biomedical Engineering PAS in Warsaw in 2019
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
Nanoemulsion technology has proven a valuable tool for fabrication of nanoparticles for bone regeneration applications
Summary
Resulting nanoemulsion has lower Gibbs free energy compared to the separated state.[112] Organic phases used in spontaneous nanoemulsification methods typically contain low percentage of oil and high percentage of solvent (high solvent/oil ratio), which increases the rate of solvent diffusion and intensity of turbulence[142] and results in formation of smaller droplets.
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