Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan 33302, Republic of China.
J Biomater Sci Polym Ed. 2010;21(3):359-76. doi: 10.1163/156856209X416980.
Due to its innocuous nature, hyaluronic acid (HA) is one of the most commonly used biopolymers for ophthalmic applications. We recently developed a cell sheet delivery system using carbodiimide cross-linked HA carriers. Chemical cross-linking provides an improvement in stability of polymer gels, but probably causes toxic side-effects. The aim of this study was to investigate the ocular biocompatibility of HA hydrogels cross-linked by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC). HA discs without cross-linking and glutaraldehyde (GTA) cross-linked HA samples were used for comparison. The disc implants were inserted in the anterior chamber of rabbit eyes for 24 weeks and characterized by slit-lamp biomicroscopy, histology and scanning electron microscopy. The ophthalmic parameters obtained from biomicroscopic examinations were also scored to provide a quantitative grading system. Results of this study showed that the HA discs cross-linked with EDC had better ocular biocompatibility than those with GTA. The continued residence of GTA cross-linked HA implants in the intraocular cavity elicited severe tissue responses and significant foreign body reactions, whereas no adverse inflammatory reaction was observed after contact with non-cross-linked HA or EDC cross-linked HA samples. It is concluded that the cross-linking agent type gives influence on ocular biocompatibility of cell carriers and the EDC-HA hydrogel is an ideal candidate for use as an implantable material in cell sheet delivery applications.
由于其无害的性质，透明质酸（HA）是最常用于眼科应用的生物聚合物之一。我们最近开发了一种使用碳化二亚胺交联的 HA 载体的细胞片输送系统。化学交联提供了聚合物凝胶稳定性的改善，但可能会引起毒性副作用。本研究的目的是研究通过 1-乙基-3-（3-二甲基氨基丙基）碳化二亚胺（EDC）交联的 HA 水凝胶的眼部生物相容性。未交联的 HA 圆盘和戊二醛（GTA）交联的 HA 样品用于比较。将圆盘植入物插入兔眼前房 24 周，并通过裂隙灯生物显微镜、组织学和扫描电子显微镜进行表征。还对生物显微镜检查获得的眼科参数进行评分，提供定量分级系统。本研究结果表明，与 GTA 交联的 HA 圆盘相比，用 EDC 交联的 HA 圆盘具有更好的眼部生物相容性。在眼内腔中继续存在 GTA 交联的 HA 植入物会引起严重的组织反应和明显的异物反应，而与未交联的 HA 或 EDC 交联的 HA 样品接触后未观察到不良反应性炎症反应。结论是交联剂类型会影响细胞载体的眼部生物相容性，EDC-HA 水凝胶是作为细胞片输送应用中可植入材料的理想候选物。
