Myung David, Koh Wongun, Bakri Amit, Zhang Fan, Marshall Amanda, Ko Jungmin, Noolandi Jaan, Carrasco Michael, Cochran Jennifer R, Frank Curtis W, Ta Christopher N
Department of Ophthalmology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5080, USA.
Biomed Microdevices. 2007 Dec;9(6):911-22. doi: 10.1007/s10544-006-9040-4.
We describe the design and fabrication of an artificial cornea based on a photolithographically patterned hydrogel construct, and demonstrate the adhesion of corneal epithelial and fibroblast cells to its central and peripheral components, respectively. The design consists of a central "core" optical component and a peripheral tissue-integrable "skirt." The core is composed of a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) double-network with high strength, high water content, and collagen type I tethered to its surface. Interpenetrating the periphery of the core is a microperforated, but resilient poly(hydroxyethyl acrylate) (PHEA) hydrogel skirt that is also surface-modified with collagen type I. The well-defined microperforations in the peripheral component were created by photolithography using a mask with radially arranged chrome discs. Surface modification of both the core and skirt elements was accomplished through the use of a photoreactive, heterobifunctional crosslinker. Primary corneal epithelial cells were cultured onto modified and unmodified PEG/PAA hydrogels to evaluate whether the central optic material could support epithelialization. Primary corneal fibroblasts were seeded onto the PHEA hydrogels to evaluate whether the peripheral skirt material could support the adhesion of corneal stromal cells. Cell growth in both cases was shown to be contingent on the covalent tethering of collagen. Successful demonstration of cell growth on the two engineered components was followed by fabrication of core-skirt constructs in which the central optic and peripheral skirt were synthesized in sequence and joined by an interpenetrating diffusion zone.
我们描述了一种基于光刻图案化水凝胶构建体的人工角膜的设计与制造，并分别证明了角膜上皮细胞和成纤维细胞对其中心和周边组件的粘附。该设计由一个中心“核心”光学组件和一个周边可与组织整合的“裙边”组成。核心由具有高强度、高含水量且表面 tethered 有 I 型胶原蛋白的聚（乙二醇）/聚（丙烯酸）（PEG/PAA）双网络构成。贯穿核心周边的是一个微穿孔但有弹性的聚（丙烯酸羟乙酯）（PHEA）水凝胶裙边，其表面也用 I 型胶原蛋白进行了修饰。周边组件中明确的微穿孔是通过使用带有径向排列铬盘的掩膜进行光刻形成的。核心和裙边元件的表面修饰是通过使用光反应性异双功能交联剂完成的。将原代角膜上皮细胞培养在修饰和未修饰的 PEG/PAA 水凝胶上，以评估中心光学材料是否能支持上皮形成。将原代角膜成纤维细胞接种到 PHEA 水凝胶上，以评估周边裙边材料是否能支持角膜基质细胞的粘附。在这两种情况下，细胞生长都显示取决于胶原蛋白的共价 tethering。在两个工程组件上成功证明细胞生长后，制造了核心 - 裙边构建体，其中中心光学组件和周边裙边依次合成，并通过互穿扩散区连接。
