Three-dimensional microchannels in biodegradable polymeric films for control orientation and phenotype of vascular smooth muscle cells
Three-dimensional microchannels in biodegradable polymeric films for control orientation and phenotype of vascular smooth muscle cells
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DOI：
10.1089/ten.2006.12.2229
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发表时间：
2006-08-01
影响因子：
--
通讯作者：
Chan, Vincent
中科院分区：
文献类型：
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作者：
Shen, Jin Ye;Chan-Park, Mary B.;Chan, Vincent
目前小直径组织工程血管（TEBV）的机械强度和血管活性差仍然是未解决的问题。鉴于平滑肌细胞 (SMC) 的可塑性，当前支架技术的主要局限性之一是难以在体外控制 SMC 表型转变。合成表型使细胞能够快速增殖并产生细胞外基质 (ECM)，而有组织的 ECM 向收缩表型的转变最终会提供功能性血管。在这项研究中，使用液体UV可聚合生物可降解大分子单体（聚（ε-己内酯-r-L-丙交酯-r-乙交酯）二丙烯酸酯）成功地对由高纵横比（8）微壁分隔的3D深（65μm）和宽微通道进行了紫外（UV）微压花，并验证了不同通道宽度（40-160μm）对SMC的体外引导效果。结果表明，在较宽的微通道（80-160μm宽）中培养的SMC从成纤维细胞形态和随机取向转变为纺锤形形态，并沿着微通道方向排列，接近汇合，细胞密度与无图案薄膜相似。此外，发现在微图案上生长的 SMC 接近汇合时平滑肌 α-肌动蛋白的表达增强，这表明表型转变为更具收缩性的表型。这些薄膜具有柔韧性，可以折叠成管状和层状结构，用于小直径 TEBV 以及食道或肠等其他器官的组织工程。这些结果表明，这些微图案合成可生物降解支架可能有助于引导 SMC 生长成功能性小直径血管移植物。
The poor mechanical strength and vasoactivity of current small-diameter tissue engineered blood vessels (TEBVs) remain unsolved problems. Given the plasticity of smooth muscle cells (SMCs), 1 of the main limitations of current scaffolding techniques is the difficulty in controlling SMC phenotype shifts in vitro. A synthetic phenotype allows the cells to rapidly proliferate and produce extracellular matrix (ECM), whereas a shift to contractile phenotype with organized ECM ultimately provides a functional blood vessel. In this study, 3D deep (65 mu m) and wide microchannels separated by high-aspect ratio (8) microwalls were successfully ultraviolet (UV) microembossed using a liquid UV polymerizable biodegradable macromer (poly(epsilon-caprolactone-r-L-lactide-r-glycolide) diacrylate) and the in vitro guidance effects of varying channel width (40-160 mu m) on SMCs were verified. The results show that SMCs cultured in the wider microchannels (80-160 mu m wide) switch from fibroblast morphology and random orientation to spindle-shaped morphology, and align along the direction of the microchannel nearing confluence achieved with similar cell density to unpatterned film. Further, an enhanced expression of smooth muscle alpha-actin of SMCs grown on micropatterns was found nearing confluence, which demonstrates a phenotype shift to a more contractile phenotype. These films are flexible and can be folded into tubular and lamellar structures for tissue engineering of small-diameter TEBVs as well as other organs such as esophagus or intestine. These results suggest that these micropatterned synthetic biodegradable scaffolds may be useful for guiding SMCs to grow into functional, small-diameter vascular grafts.