Engineering of multifunctional gels integrating highly efficient growth factor delivery with endothelial cell transplantation
Engineering of multifunctional gels integrating highly efficient growth factor delivery with endothelial cell transplantation
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DOI：
10.1096/fj.08-108803
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发表时间：
2008-08-01
期刊：
影响因子：
4.8
通讯作者：
Saltzman, W. Mark
中科院分区：
文献类型：
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作者：
Jay, Steven M.;Shepherd, Benjamin R.;Saltzman, W. Mark
Bcl-2-转导的人脐静脉内皮细胞（EC）在蛋白质凝胶移植到腓肠肌改善局部再灌注免疫缺陷小鼠主机诱导后肢缺血。我们测试了这一假设，即纳入本地，持续的生长因子交付可以增强和加速这种效果。组织工程支架通常使用合成聚合物来实现蛋白质的受控释放，但大多数合成递送系统具有重大局限性，最显著的是疏水性和低效的蛋白质装载。在这里，我们报告了一种新的海藻酸盐为基础的血管内皮生长因子-A（165）（VEGF），表现出上级的负载效率和物理性能，以前的系统在体外输送系统的发展。在体内，从蛋白质凝胶内的藻酸盐微粒释放的VEGF具有生物活性，并且当与EC移植结合时，导致移植细胞在28天时的存活增加。所述的复合移植物还改善了早期（14天）组织灌注和晚期（28天）肌肉肌红蛋白表达，这是从缺血中恢复的标志，与EC移植和VEGF单独递送相比。我们的结论是，我们改进的方法，以持续的VEGF输送组织工程是有用的，在体内和整合的高效率的蛋白质输送增强了蛋白凝胶为基础的EC移植的治疗效果。
Transplantation of Bcl-2-transduced human umbilical vein endothelial cells (ECs) in protein gels into the gastrocnemius muscle improves local reperfusion in immunodeficient mouse hosts with induced hind limb ischemia. We tested the hypothesis that incorporation of local, sustained growth factor delivery could enhance and accelerate this effect. Tissue engineering scaffolds often use synthetic polymers to enable controlled release of proteins, but most synthetic delivery systems have major limitations, most notably hydrophobicity and inefficient protein loading. Here, we report the development of a novel alginate-based delivery system for vascular endothelial growth factor-A(165) (VEGF) that exhibits superior loading efficiency and physical properties to previous systems in vitro. In vivo, VEGF released from alginate microparticles within protein gels was biologically active and, when combined with EC transplantation, led to increased survival of transplanted cells at 28 days. The composite graft described also improved early (14 days) tissue perfusion and late (28 days) muscle myoglobin expression, a sign of recovery from ischemia, compared with EC transplantation and VEGF delivery separately. We conclude that our improved approach to sustained VEGF delivery in tissue engineering is useful in vivo and that the integration of high efficiency protein delivery enhances the therapeutic effect of protein gel-based EC transplantation.