Dual growth factor delivery from degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds for cartilage tissue engineering
Dual growth factor delivery from degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds for cartilage tissue engineering
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DOI：
10.1016/j.jconrel.2004.07.004
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发表时间：
2005-01-03
影响因子：
10.8
通讯作者：
Mikos, AG
中科院分区：
文献类型：
--
作者：
Holland, TA;Tabata, Y;Mikos, AG
这项工作描述了一种非侵入性的方法，以控制的方式同时向受损的软骨组织输送胰岛素样生长因子-1(IGF-1)和转化生长因子-β1(TGF-β1)。这一新的递送技术使用了水溶性聚合物低聚(聚乙二醇富马酸酯)(OPF)来制备包裹明胶微粒的可生物降解水凝胶。释放研究首先考察了明胶等电点(IEP)和交联度对这些微粒释放IGF-1的影响。在胶原酶存在下，高交联度酸性明胶(IEP=5.0)在第28天有95.2+/-2.9%的累积释放量，而交联度较低的微球和交联度较低的微球仅在第6天就有相似的释放量。将这些高度交联的微粒包裹在OPF网络中提供了进一步控制释放的手段，将含胶原酶的PBS的最终累积释放减少到70.2+/-4.7%。OPF-明胶微粒复合材料的最终释放值可以通过在这些结构中加入较少的交联性、未负载的微粒来改变。最后，通过将生长因子负载到OPF水凝胶相或明胶微粒相，将该技术扩展到IGF-1和转化生长因子-β1的双重输送。通过改变生长因子的载药阶段和微粒的交联度，成功地控制了微球的释放曲线。例如，通过将转化生长因子-β1负载到明胶微粒相中，实现了10.8+/-0.7%的突释，而将该生长因子负载到OPF水凝胶相中，获得了25.2+/-1.5%的突释。在任何一种系统中，IGF-1的同时缓慢释放都是通过选择性地将这种蛋白质装载到高度交联的包裹微粒中来实现的，为期4周。这些结果证明了这些系统在未来的研究中的用途，以评估多种生长因子在软骨修复中的相互作用和时间进程。(C)2004爱思唯尔B.V.保留所有权利。
This work describes the development of a non-invasive means of simultaneously delivering insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-beta 1) to injured cartilage tissue in a controlled manner. This novel delivery technology employs the water-soluble polymer, oligo(poly(ethylene glycol) fumarate) (OPF), in the fabrication of biodegradable hydrogels which encapsulate gelatin microparticles. Release studies first examined the effect of gelatin isoelectric point (IEP) and crosslinking extent on IGF-1 release from these microparticles. In the presence of collagenase, highly crosslinked, acidic gelatin (IEP=5.0) provided sustained release of IGF-1, 95.2 +/- 2.9% cumulative release at day 28, while less crosslinked microparticles and microparticles of alternate IEP exhibited similar release values after only 6 days. Encapsulation of these highly crosslinked microparticles in a network of OPF provided a means to further control release, reducing final cumulative release to 70.2 +/- 4.7% in collagenase-containing PBS. Final release values from OPF-gelatin microparticle composites could be altered by incorporating less crosslinked, non-loaded microparticles within these constructs. Finally, this technology was extended to the dual delivery of IGF-1 and TGF-beta 1 by loading these growth factors into either the OPF hydrogel phase or gelatin microparticle phase of composites. Release profiles were successfully manipulated by altering the phase of growth factor loading and microparticle crosslinking extent. For instance, by loading TGF-beta 1 into the gelatin microparticle phase, a burst release of 10.8 +/- 0.7% was achieved, while loading this growth factor into the OPF hydrogel phase resulted in a burst release of 25.2 +/- 1.5%. With either system, simultaneous, slow release of IGF-1 over a 4-week period was accomplished by selectively loading this protein into highly crosslinked, encapsulated microparticles. These results demonstrate the utility of these systems in future Studies to assess the interplay and time course of multiple growth factors in cartilage repair. (c) 2004 Elsevier B.V. All rights reserved.