Liu Tie, Wu Gang, Zheng Yuanna, Wismeijer Daniel, Everts Vincent, Liu Yuelian
Clin Oral Implants Res. 2014 Dec;25(12):1412-21. doi: 10.1111/clr.12283.
In this study, a novel biomimetic calcium phosphate bone substitute (BioCaP) is introduced as a dual-drug release system with two drug/protein delivery modes: protein is incorporated into (i) the interior of BioCaP (an internal depot); and (ii) a superficial calcium phosphate coating on BioCaP (a surface-coated depot). Our aim is to investigate each of the two delivery modes of BioCaP. Our hypotheses are that (i) both of the drug delivery modes, in in vitro as well as in vivo environment, can achieve a sustained cell-mediated protein release; and (ii) BioCaP with these two delivery modes with incorporated bone morphogenetic protein-2 (BMP-2) promotes bone formation.
Tablets of BioCaP were prepared with different carrying modes using bovine serum albumin (BSA) as model protein. The release of this protein was analysed (n = 6 per group). Granules of BioCaP with different carrying modes of BMP-2 were implanted subcutaneously in rats (n = 6 animals per group). Samples were collected after 5 weeks for histomorphometric analysis.
In vitro data showed that the internal and surface-coated depots of BSA resulted in a sustained osteoclast-mediated release, while the adsorbed BSA was rapidly released, and this release was not affected by osteoclasts. In vivo data showed that the volume densities of bone, bone marrow, and blood vessels were significantly higher in samples where BMP-2 was incorporated internally or in the coating compared with granules with adsorbed growth factor. Osteoclast-like cells were associated with the granules, and resorption lacunae were frequently observed.
It is shown that different modes of incorporation of BMP-2 on and in BioCaP granules have a beneficial effect on the formation of ectopic bone. This dual-drug release system makes BioCaP granule a promising tool for delivering multiple therapeutic agents for different clinical applications.
在本研究中，引入了一种新型仿生磷酸钙骨替代物（BioCaP）作为具有两种药物/蛋白质递送模式的双药释放系统：蛋白质被掺入（i）BioCaP内部（内部贮库）；以及（ii）BioCaP上的表面磷酸钙涂层（表面涂层贮库）。我们的目的是研究BioCaP的两种递送模式。我们的假设是：（i）在体外以及体内环境中，两种药物递送模式均能实现细胞介导的蛋白质持续释放；（ii）具有这两种递送模式并掺入骨形态发生蛋白-2（BMP-2）的BioCaP可促进骨形成。
使用牛血清白蛋白（BSA）作为模型蛋白，以不同的携带模式制备BioCaP片剂。分析该蛋白质的释放情况（每组n = 6）。将具有不同BMP-2携带模式的BioCaP颗粒皮下植入大鼠体内（每组n = 6只动物）。5周后收集样本进行组织形态计量学分析。
体外数据表明，BSA的内部和表面涂层贮库导致破骨细胞介导的持续释放，而吸附的BSA则迅速释放，且这种释放不受破骨细胞影响。体内数据表明，与吸附生长因子的颗粒相比，内部或涂层中掺入BMP-2的样本中骨、骨髓和血管的体积密度显著更高。破骨细胞样细胞与颗粒相关，且经常观察到吸收陷窝。
结果表明，BMP-2在BioCaP颗粒上和内部的不同掺入模式对异位骨形成具有有益作用。这种双药释放系统使BioCaP颗粒成为用于不同临床应用递送多种治疗剂的有前景的工具。
