When Nothing Turns Itself Inside out and Becomes Something: Coating Poly(Lactic--Glycolic Acid) Spheres with Hydroxyapatite Nanoparticles vs. the Other Way Around.

To stabilize drugs physisorbed on the surface of hydroxyapatite (HAp) nanoparticles and prevent burst release, these nanoparticles are commonly coated with polymers. Bioactive HAp, however, becomes shielded from the surface of such core/shell entities, which partially defeats the purpose of using it. The goal of this study was to assess the biological and pharmacokinetic effects of inverting this classical core/shell structure by coating poly(lactic--glycolic acid) (PLGA) spheres with HAp nanoparticles. The HAp shell did not hinder the release of vancomycin; rather, it increased the release rate to a minor degree, compared to that from undecorated PLGA spheres. The decoration of PLGA spheres with HAp induced lesser mineral deposition and lesser upregulation of osteogenic markers compared to those induced by the composite particles where HAp nanoparticles were embedded inside the PLGA spheres. This was explained by homeostatic mechanisms governing the cell metabolism, which ensure than the sensation of a product of this metabolism in the cell interior or exterior is met with the reduction in the metabolic activity. The antagonistic relationship between proliferation and bone production was demonstrated by the higher proliferation rate of cells challenged with HAp-coated PLGA spheres than of those treated with PLGA-coated HAp. It is concluded that the overwhelmingly positive response of tissues to HAp-coated biomaterials for bone replacement is unlikely to be due to the direct induction of new bone growth in osteoblasts adhering to the HAp coating. Rather, these positive effects are consequential to more elementary aspects of cell attachment, mechanotransduction, and growth at the site of contact between the HAp-coated material and the tissue.