Clark Paul A, Moioli Eduardo K, Sumner D Rick, Mao Jeremy J
Department of Neurological Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
FASEB J. 2008 Jun;22(6):1684-93. doi: 10.1096/fj.07-094789. Epub 2008 Jan 15.
The common premise of synthetic implants in the restoration of diseased tissues and organs is to use inert and solid materials. Here, a porous titanium implant was fabricated for the delivery of microencapsulated bioactive cues. Control-released transforming growth factor-beta1 (TGF-beta1) promoted the proliferation and migration of human mesenchymal stem cells into porous implants in vitro. At 4 wk of implantation in the rabbit humerus, control-released TGF-beta1 from porous implants significantly increased bone-to-implant contact (BIC) by 96% and bone ingrowth by 50% over placebos. Control-released 100 ng TGF-beta1 induced equivalent BIC and bone ingrowth to adsorbed 1 microg TGF-beta1, suggesting that controlled release is effective at 10-fold less drug dose than adsorption. Histomorphometry, scanning electron microscopy, and microcomputed tomography showed that control-released TGF-beta1 enhanced bone ingrowth in the implant's pores and surface. These findings suggest that solid prostheses can be transformed into porous implants to serve as drug delivery carriers, from which control-released bioactive cues augment host tissue integration.
合成植入物用于修复病变组织和器官的共同前提是使用惰性和固态材料。在此，制备了一种多孔钛植入物用于递送微囊化生物活性信号。控释转化生长因子-β1（TGF-β1）在体外促进人间充质干细胞向多孔植入物的增殖和迁移。在兔肱骨植入4周时，多孔植入物控释的TGF-β1与安慰剂相比，显著增加骨与植入物接触（BIC）96%，骨长入增加50%。控释100 ng TGF-β1诱导的BIC和骨长入与吸附1 μg TGF-β1相当，表明控释在药物剂量比吸附少10倍时仍有效。组织形态计量学、扫描电子显微镜和微计算机断层扫描显示，控释的TGF-β1增强了植入物孔隙和表面的骨长入。这些发现表明，固态假体可转化为多孔植入物作为药物递送载体，从中控释生物活性信号可增强宿主组织整合。
