MMP-sensitive PEG hydrogel modified with RGD promotes bFGF, VEGF and EPC-mediated angiogenesis
MMP-sensitive PEG hydrogel modified with RGD promotes bFGF, VEGF and EPC-mediated angiogenesis
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DOI：
10.3892/etm.2019.7885
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发表时间：
2019-10-01
影响因子：
2.7
通讯作者：
Duan, Deyu
中科院分区：
文献类型：
--
作者：
Ouyang, Liu;Dan, Yang;Duan, Deyu
创伤性软组织缺损如压疮、慢性皮肤溃疡、肢体坏死、骨坏死等骨科缺血性疾病是骨科临床上最棘手、最常见的问题，传统的治疗方法不能令人满意。本研究设计了共价结合精氨酸甘氨酰天冬氨酸(RGD)的聚乙二醇聚乙二醇水凝胶。将内皮祖细胞与血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(BFGF)一起包裹在修饰的水凝胶中。结果表明，改性后的水凝胶具有良好的力学性能，适合作为缓释载体。RGD改性显著提高了EPC的生物相容性。血管内皮生长因子和碱性成纤维细胞生长因子的包裹增强了内皮祖细胞的黏附，促进了细胞外基质的产生，促进了内皮祖细胞的增殖。此外，碱性成纤维细胞生长因子和血管内皮细胞生长因子可诱导血管生成。生长因子和内皮祖细胞在水凝胶中的结合表现出很强的协同作用，提高了生物相容性。本研究结果为软组织缺损如骨外露、慢性皮肤溃疡、压疮、肢体坏死、骨坏死等缺血性疾病提供了一种潜在的新的治疗方法。
Traumatic soft tissue defects such as bedsores, chronic skin ulcers, limb necrosis, osteonecrosis and other ischemic orthopedic diseases are the most clinically intractable and common problems in orthopedics due to unsatisfactory conventional treatments. The present study designed poly(ethylene glycol; PEG) hydrogels with covalently binded arginylglycylaspartic acid (RGD). Endothelial progenitor cells (EPCs) were encapsulated in the modified hydrogel along with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Results demonstrated that the modified hydrogel displayed good mechanical properties appropriate for a sustained release carrier. RGD modification significantly promoted EPC biocompatibility. VEGF and bFGF encapsulation enhanced the adhesion of EPCs, promoted the production of extracellular matrix and facilitated EPC proliferation. In addition, bFGF and VEGF induced angiogenesis. The combination of growth factors and EPCs in the hydrogel displayed a strong synergy to improve biocompatibility. The present results provided a potential novel treatment approach for soft tissue defects such as bone exposure, chronic skin ulcers, bedsores, limb necrosis, osteonecrosis and other ischemic diseases.