Uskoković Vuk, Wu Victoria M
TardigradeNano LLC., 7 Park Vista, Irvine, CA 92604, USA.
Department of Mechanical Engineering, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182, USA.
J Funct Biomater. 2022 Jul 23;13(3):102. doi: 10.3390/jfb13030102.
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.
为了稳定物理吸附在羟基磷灰石（HAp）纳米颗粒表面的药物并防止其突发释放，这些纳米颗粒通常会用聚合物进行包被。然而，具有生物活性的HAp会被这种核/壳结构的表面所屏蔽，这在一定程度上违背了使用它的初衷。本研究的目的是评估通过用HAp纳米颗粒包被聚乳酸-乙醇酸共聚物（PLGA）微球来颠倒这种经典核/壳结构所产生的生物学和药代动力学效应。与未修饰的PLGA微球相比，HAp壳层并未阻碍万古霉素的释放；相反，它在一定程度上提高了释放速率。与HAp纳米颗粒嵌入PLGA微球内部的复合颗粒相比，用HAp修饰PLGA微球诱导的矿物质沉积较少，成骨标志物的上调也较少。这可以通过控制细胞代谢的稳态机制来解释，该机制确保细胞内或细胞外这种代谢产物的感知与代谢活性的降低相匹配。用HAp包被的PLGA微球处理的细胞比用PLGA包被的HAp处理的细胞具有更高的增殖率，这证明了增殖与骨生成之间的拮抗关系。研究得出结论，组织对用于骨替代的HAp包被生物材料的压倒性积极反应不太可能是由于直接诱导粘附在HAp涂层上的成骨细胞中新骨生长。相反，这些积极作用是HAp包被材料与组织接触部位细胞附着、机械转导和生长等更基本方面的结果。
