Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor
Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor
复制标题
DOI：
10.1016/j.biomaterials.2005.03.012
复制
发表时间：
2005-10-01
期刊：
影响因子：
14
通讯作者：
Prestwich, GD
中科院分区：
文献类型：
--
作者：
Cai, SS;Liu, YC;Prestwich, GD
通过用巯基修饰的透明质酸（HA）或硫酸软骨素（CS）与聚（乙二醇）二丙烯酸酯（PEGDA）交联巯基修饰的肝素类似物来产生细胞外基质（ECM）的合成水凝胶模拟物。共价结合的肝素提供硫酸乙酰肝素蛋白聚糖的可交联类似物，从而提供能够控制释放碱性成纤维细胞生长因子（bFGF）的多价生物材料。水凝胶含有> 97%的水，并在< 10分钟内迅速形成。与低至1%（w/w）的共价结合肝素（相对于总糖胺聚糖含量），在体外释放的bFGF的速率大大降低。释放的总bFGF随着肝素百分比的降低而增加;观察到无肝素水凝胶基本上定量释放bFGF。此外，水凝胶释放的bFGF保留其生物活性的55%，长达28天，如通过细胞增殖测定所确定的。最后，当这些水凝胶植入Balb/c小鼠的皮下袋中时，含有bFGF和交联肝素的HA和CS水凝胶的新血管形成显著增加。相比之下，缺乏bFGF或交联肝素的水凝胶几乎没有显示出新血管形成的增加。因此，共价连接的，含肝素的糖胺聚糖水凝胶，可以注射和交联原位构成非常有前途的新材料的肝素结合生长因子在体内的控制释放。(c)2005爱思唯尔有限公司保留所有权利。
Synthetic hydrogel mimics of the extracellular matrix (ECM) were created by crosslinking a thiol-modified analog of heparin with thiol-modified hyaluronan (HA) or chondroitin sulfate (CS) with poly(ethylene glycol) diacrylate (PEGDA). The covalently bound heparin provided a crosslinkable analog of a heparan sulfate proteoglycan, thus providing a multivalent biomaterial capable of controlled release of basic fibroblast growth factor (bFGF). Hydrogels contained > 97% water and formed rapidly in < 10 min. With as little as 1% (w/w) covalently bound heparin (relative to total glycosaminoglycan content), the rate of release of bFGF in vitro was substantially reduced. Total bFGF released increased with lower percentages of heparin; essentially quantitative release of bFGF was observed from heparin-free hydrogels. Moreover, the hydrogel-released bFGF retained 55% of its biological activity for up to 28 days as determined by a cell proliferation assay. Finally, when these hydrogels were implanted into subcutaneous pockets in Balb/c mice, neovascularization increased dramatically with HA and CS hydrogels that contained both bFGF and crosslinked heparin. In contrast, hydrogels lacking bFGF or crosslinked heparin showed little increase in neovascularization. Thus, covalently linked, heparin-containing glycosaminoglycan hydrogels that can be injected and crosslinked in situ constitute highly promising new materials for controlled release of heparin-binding growth factors in vivo. (c) 2005 Elsevier Ltd. All rights reserved.