Modulating smooth muscle cell response by the release of TGFβ2 from tubular scaffolds for vascular tissue engineering
Modulating smooth muscle cell response by the release of TGFβ2 from tubular scaffolds for vascular tissue engineering
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DOI：
10.1016/j.jconrel.2019.02.024
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发表时间：
2019-04-10
影响因子：
10.8
通讯作者：
Geest, Vande J. P.
中科院分区：
文献类型：
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作者：
Ardila, D. C.;Tamimi, E.;Geest, Vande J. P.
小直径组织工程化血管移植物（TEVG）用于治疗冠心病已引起广泛关注。一个适当设计的脱细胞和可生物降解的TEVG必须鼓励血管平滑肌细胞（SMC）的浸润和生长。我们的研究小组先前已经表明，增加TGF β 2的水平可以不同地调节SMC的迁移和增殖。在这项研究中，使用不同比例的明胶/聚己内酯（PCL）制备了载有TGF β 2的管状电纺支架，从而得到具有适合组织向内生长的多孔纳米编织结构的支架。评估支架形态、降解速率、TGF β 2释放动力学和生物活性。TGF β 2成功地整合到电纺生物材料中，这导致在42天的过程中根据明胶/PCL比率的差异释放曲线。明胶含量较高的支架中TGF β 2洗脱率较高，这可能与明胶在培养基中的生物降解有关。释放的TGF β 2的生物活性通过其影响SMC增殖的能力作为其浓度的函数来评价。与不含TGF β 2的支架相比，接种在负载TGF β 2的支架上的SMC在培养5天后也显示出更高的密度和浸润。我们的研究结果表明，合成和天然聚合物在静电纺丝混合物的比例可以用来调整TGF β 2的释放。该方法可用于智能地调节明胶/PCL支架中的SMC响应，使得负载TGF β 2的导管对于心血管组织工程应用具有吸引力。
Tissue engineering has gained considerable attention in the development of small diameter tissue engineered vascular grafts (TEVGs) for treating coronary heart disease. A properly designed acellular and biodegradable TEVG must encourage the infiltration and growth of vascular smooth muscle cells (SMCs). Our group has previously shown that increasing levels of TGF beta 2 can differentially modulate SMC migration and proliferation. In this study, tubular electrospun scaffolds loaded with TGF beta 2 were fabricated using various ratios of gelatin/polycaprolactone (PCL), resulting in scaffolds with porous nano-woven architecture suitable for tissue ingrowth. Scaffold morphology, degradation rate, TGF beta 2 release kinetics, and bioactivity were assessed. TGF beta 2 was successfully integrated into the electrospun biomaterial that resulted in a differential release profile depending on the gelatin/PCL ratio over the course of 42 days. Higher TGF beta 2 elution was obtained in scaffolds with higher gelatin content, which may be related to the biodegradation of gelatin in culture media. The biological activity of the released TGF beta 2 was evaluated by its ability to affect SMC proliferation as a function of its concentration. SMCs seeded on TGF beta 2-loaded scaffolds also showed higher densities and infiltration after 5 days in culture as compared to scaffolds without TGF beta 2. Our results demonstrate that the ratio of synthetic and natural polymers in electrospun blends can be used to tune the release of TGF beta 2. This method can be used to intelligently modulate the SMC response in gelatin/PCL scaffolds making the TGF beta 2-loaded conduits attractive for cardiovascular tissue engineering applications.