Khademhosseini Ali, Eng George, Yeh Judy, Fukuda Junji, Blumling James, Langer Robert, Burdick Jason A
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Biomed Mater Res A. 2006 Dec 1;79(3):522-32. doi: 10.1002/jbm.a.30821.
Micropatterning of hydrogels is potentially useful for a variety of applications, including tissue engineering, fundamental biological studies, diagnostics, and high-throughput screening. Although synthetic polymers have been developed for these applications, natural polymers such as polysaccharides may have advantages for biological samples and cell-based devices because they are natural components of the in vivo microenvironment. In this study, we synthesized and used hyaluronic acid (HA) modified with photoreactive methacrylates to fabricate microstructures as functional components of microfabricated devices. To demonstrate the universality of this approach, two types of microstructures were formed. In the first approach, HA microstructures were fabricated and used as docking templates to enable the subsequent formation of cell microarrays within low shear stress regions of the patterns. Cells within these microwells remained viable, could generate spheroids, and could be retrieved using mechanical disruption. In the second approach, cells were encapsulated directly within the HA hydrogels. Arrays of viable embryonic stem (ES) cells or fibroblasts were encapsulated within HA hydrogels and could later be recovered using enzymatic digestion of the microstructures. These results demonstrate that it is possible to incorporate photocrosslinkable HA, a natural, versatile, degradable, and biocompatible biopolymer, into micro-electromechanical systems.
水凝胶的微图案化在包括组织工程、基础生物学研究、诊断和高通量筛选等多种应用中具有潜在用途。尽管已经开发出合成聚合物用于这些应用，但诸如多糖之类的天然聚合物对于生物样品和基于细胞的装置可能具有优势，因为它们是体内微环境的天然成分。在本研究中，我们合成并使用用光反应性甲基丙烯酸酯修饰的透明质酸（HA）来制造微结构，作为微制造装置的功能组件。为了证明这种方法的通用性，形成了两种类型的微结构。在第一种方法中，制造HA微结构并将其用作对接模板，以便在图案的低剪切应力区域内随后形成细胞微阵列。这些微孔内的细胞保持存活，能够生成球体，并且可以通过机械破坏来回收。在第二种方法中，细胞被直接封装在HA水凝胶内。存活的胚胎干细胞（ES）或成纤维细胞阵列被封装在HA水凝胶内，随后可以通过对微结构进行酶消化来回收。这些结果表明，将可光交联的HA（一种天然、通用、可降解且生物相容的生物聚合物）纳入微机电系统是可能的。
