Materials Science Program, University of Wisconsin, Madison, WI 53706, USA.
Acta Biomater. 2012 Mar;8(3):1117-24. doi: 10.1016/j.actbio.2011.11.028. Epub 2011 Dec 2.
β-Tricalcium phosphate (β-TCP) is an attractive ceramic for bone tissue repair because of its similar composition to bone mineral and its osteoconductivity. However, compared with other ceramics β-TCP has a rapid and uncontrolled rate of degradation. In the current study β-TCP granules were mineral coated with the aim of influencing the dissolution rate of β-TCP, and also to use the coating as a carrier for controlled release of the growth factors recombinant human vascular endothelial growth factor (rhVEGF), modular VEGF peptide (mVEGF), and modular bone morphogenetic protein 2 peptide (mBMP2). The biomineral coatings were formed by heterogeneous nucleation in aqueous solution using simulated body fluid solutions with varying concentrations of bicarbonate (HCO(3)). Our results demonstrate that we could coat β-TCP granules with mineral layers possessing different dissolution properties. The presence of a biomineral coating delays the dissolution rate of the β-TCP granules. As the carbonate (CO(3)(2-)) content in the coating was increased the dissolution rate of the coated β-TCP also increased, but remained slower than the dissolution of uncoated β-TCP. In addition, we showed sustained release of multiple growth factors, with release kinetics that were controllable by varying the identity of the growth factor or the CO(3)(2-) content in the mineral coating. Released rhVEGF induced human umbilical vein endothelial cell (HUVEC) proliferation, and mVEGF enhanced migration of mouse embryonic endothelial cells in a scratch wound healing assay, indicating that each released growth factor was biologically active.
β-磷酸三钙(β-TCP)因其与骨矿物质相似的组成和骨诱导性而成为一种有吸引力的骨组织修复陶瓷。然而,与其他陶瓷相比,β-TCP 的降解速度快且不可控。在本研究中,β-TCP 颗粒被矿物涂层包裹,目的是影响β-TCP 的溶解速率,并利用涂层作为生长因子重组人血管内皮生长因子(rhVEGF)、模块化 VEGF 肽(mVEGF)和模块化骨形态发生蛋白 2 肽(mBMP2)的控制释放载体。生物矿物涂层是通过在含有不同浓度碳酸氢盐(HCO(3))的模拟体液溶液中在水溶液中异质成核形成的。我们的结果表明,我们可以用具有不同溶解性能的矿物层来包裹β-TCP 颗粒。生物矿物涂层的存在会延迟β-TCP 颗粒的溶解速率。随着涂层中碳酸盐(CO(3)(2-))含量的增加,涂层β-TCP 的溶解速率也随之增加,但仍比未涂层β-TCP 的溶解速率慢。此外,我们展示了多种生长因子的持续释放,其释放动力学可通过改变生长因子的特性或矿物涂层中的 CO(3)(2-)含量来控制。释放的 rhVEGF 诱导人脐静脉内皮细胞(HUVEC)增殖,mVEGF 增强划痕愈合试验中鼠胚胎内皮细胞的迁移,表明释放的每种生长因子均具有生物活性。