Multimodal release of transforming growth factor-β1 and the BB isoform of platelet derived growth factor from PEGylated fibrin gels
Multimodal release of transforming growth factor-β1 and the BB isoform of platelet derived growth factor from PEGylated fibrin gels
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DOI：
10.1016/j.jconrel.2010.03.026
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发表时间：
2010-10-15
影响因子：
10.8
通讯作者：
Suggs, Laura J.
中科院分区：
文献类型：
--
作者：
Drinnan, Charles T.;Zhang, Ge;Suggs, Laura J.
我们设计了一种生长因子释放系统，以潜在地稳定缺血组织治疗中的新生血管。在本研究中，聚乙二醇化纤维蛋白凝胶的PDGF-BB和转化生长因子-β1的释放以不同的动力学控制。生长因子可以通过3种机制负载到聚乙二醇化的纤维蛋白凝胶中：包埋、通过同源双官能胺反应性聚乙二醇键接合以及与纤维蛋白基质的物理亲和力。PDGF-BB在凝血酶介导的交联过程中被包裹，导致扩散控制释放超过2天。转化生长因子-β1既通过聚乙二醇联接物结合，又通过物理亲和力结合到基质上，使转化生长因子-β1的释放速率延迟长达10天。此外，释放速率与凝胶降解率高度相关，表明转化生长因子-β1的释放受降解控制。因此，通过调节聚乙二醇和纤维蛋白原的摩尔比，我们能够在不改变PDGF-BB释放动力学的情况下控制转化生长因子-β1的释放速度。负载的转化生长因子-β1在释放后保持生物活性，这是通过抑制细胞增殖来证明的。该系统可以扩展到包括通过3种方案加载的生长因子，这些方案与注射系统具有不同的释放速率，从而允许在其他组合药物输送和组织工程系统中具有高度的灵活性。(C)2010爱思唯尔B.V.保留所有权利。
We designed a growth factor release system to potentially stabilize neovascularization in the treatment of ischemic tissue. In this study, the release of PDGF-BB and TGF-beta 1 was controlled with distinct kinetics from injectable PEGylated fibrin gels. Growth factors can be loaded into PEGylated fibrin gels via 3 mechanisms: entrapment, conjugation through a homobifunctional amine reactive PEG linker, and physical affinity with the fibrin matrix. PDGF-BB was entrapped during thrombin-mediated crosslinking leading to a diffusion-controlled release over 2 days. TGF-beta 1 was both conjugated through the PEG linker and bound to the matrix via physical affinity, delaying the release rate of TGF-beta 1 up to 10 days. Further, the release rate was highly correlated to gel degradation rate indicating that TGF-beta 1 release is degradation-controlled. Therefore, by modulating the molar ratio of PEG to fibrinogen, we were able to control the release rate of TGF-beta 1 without altering the release kinetics of PDGF-BB. The bioactivity of loaded TGF-beta 1 was maintained upon release as evidenced by the inhibition of cell proliferation. This system could be expanded to incorporate growth factors loaded via 3 schemes with differing release rates from an injectable system allowing for a high degree of flexibility in other combinational drug delivery and tissue engineering systems. (C) 2010 Elsevier B.V. All rights reserved.