Ardila D C, Tamimi E, Doetschman T, Wagner W R, Vande Geest J P
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ 85721, USA; BIO5 Institute, The University of Arizona, Tucson, AZ 85724, USA.
J Control Release. 2019 Apr 10;299:44-52. doi: 10.1016/j.jconrel.2019.02.024. Epub 2019 Feb 20.
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 TGFβ2 can differentially modulate SMC migration and proliferation. In this study, tubular electrospun scaffolds loaded with TGFβ2 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, TGβ2 release kinetics, and bioactivity were assessed. TGFβ2 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 TGFβ2 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 TGFβ2 was evaluated by its ability to affect SMC proliferation as a function of its concentration. SMCs seeded on TGFβ2-loaded scaffolds also showed higher densities and infiltration after 5 days in culture as compared to scaffolds without TGFβ2. Our results demonstrate that the ratio of synthetic and natural polymers in electrospun blends can be used to tune the release of TGFβ2. This method can be used to intelligently modulate the SMC response in gelatin/PCL scaffolds making the TGFβ2-loaded conduits attractive for cardiovascular tissue engineering applications.
在用于治疗冠心病的小直径组织工程血管移植物（TEVG）的开发中，组织工程已受到广泛关注。设计合理的脱细胞且可生物降解的TEVG必须促进血管平滑肌细胞（SMC）的浸润和生长。我们团队先前已表明，增加转化生长因子β2（TGFβ2）的水平可不同程度地调节SMC的迁移和增殖。在本研究中，使用不同比例的明胶/聚己内酯（PCL）制备了负载TGFβ2的管状电纺支架，得到了具有适合组织向内生长的多孔纳米编织结构的支架。评估了支架的形态、降解速率、TGFβ2释放动力学和生物活性。TGFβ2成功整合到电纺生物材料中，在42天的过程中，其释放曲线因明胶/PCL比例而异。明胶含量较高的支架中TGFβ2洗脱量更高，这可能与明胶在培养基中的生物降解有关。通过其影响SMC增殖的能力作为其浓度的函数来评估释放的TGFβ2的生物活性。与未负载TGFβ2的支架相比，接种在负载TGFβ2支架上的SMC在培养5天后也显示出更高的密度和浸润。我们的结果表明，电纺共混物中合成聚合物和天然聚合物的比例可用于调节TGFβ2的释放。该方法可用于智能调节明胶/PCL支架中的SMC反应，使负载TGFβ2的导管在心血管组织工程应用中具有吸引力。
