Porous implants as drug delivery vehicles to augment host tissue integration

Porous implants as drug delivery vehicles to augment host tissue integration
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DOI:
10.1096/fj.07-094789
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发表时间:
2008-06-01
期刊:
影响因子:
4.8
通讯作者:
Mao, Jeremy J.
Mao, Jeremy J.
中科院分区:
生物学2区
文献类型:
--
作者:
Clark, Paul A.;Moioli, Eduardo K.;Mao, Jeremy J.

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合成植入物在修复病变组织和器官中的共同前提是使用惰性和固体材料。在这里,多孔钛植入物制造的微囊化生物活性线索的交付。控释转化生长因子-β 1(TGF-β 1)促进人骨髓间充质干细胞在体外增殖和迁移到多孔植入物中。在兔肱骨植入4周时,多孔植入物中控制释放的TGF-β 1显著增加骨-植入物接触(BIC),与安慰剂相比增加了96%,骨长入增加了50%。控制释放的100 ng TGF-β 1诱导的BIC和骨向内生长与吸附的1 μ g TGF-β 1相当,表明控制释放在比吸附低10倍的药物剂量下有效。组织形态计量学、扫描电子显微镜和微型计算机断层扫描显示,控释TGF-β 1增强了种植体孔隙和表面的骨长入。这些发现表明,固体假体可以转化为多孔植入物,作为药物输送载体,从控制释放的生物活性线索增强宿主组织整合。
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-beta 1 (TGF-beta 1) 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-beta 1 from porous implants significantly increased bone- to- implant contact (BIC) by 96% and bone ingrowth by 50% over placebos. Control- released 100 ng TGF-beta 1 induced equivalent BIC and bone ingrowth to adsorbed 1 mu g TGF-beta 1, 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-beta 1 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.