纳米HA/PVA多孔复合水凝胶人工角膜在兔角膜的生物学反应

The biological response of rabbit cornea implanted with nano-HA/PVA composite hydrogel keratoprosthesis

目的观察纳米HA/PVA多孔复合水凝胶人工角膜在兔角膜内的生物学反应,了解其组织相容性。设计动物实验研究对象三组人工角膜材料:材料1为大孔纳米HA/PVA多孔复合水凝胶人工角膜;材料2为小孔纳米HA/PVA多孔复合水凝胶人工角膜;材料3为单纯PVA水凝胶人工角膜。方法选用健康新西兰大白兔21只,随机分为Ⅰ、Ⅱ、Ⅲ组(每组7只,每只兔随机选一眼)分别板层植入材料1、2、3。于术后3、8、24周通过裂隙灯、组织切片HE染色观察人工角膜在兔角膜内的生物学反应。主要指标术眼炎性反应评分,角膜新生血管出现时间及其生长面积分级评分,术后人工角膜脱出率,组织切片HE染色观察。结果术后3周时Ⅰ、Ⅱ、Ⅲ组炎性反应评分分别为1.29±0.488、1.43±0.535和2.14±0.690(P=0.027);术后8周时Ⅰ、Ⅱ、Ⅲ组新生血管平均生长面积分级评分分别为2.67±0.516、2.33±0.816和1.57±0.535(P=0.018);三组术后角膜新生血管出现时间分别为(23.17±1.72)天、(24.50±1.05)天和(29.71±1.60)天(P=0.000);三组术后因角膜溶解引起的人工角膜脱出率分别为14.29%、28.57%和42.86%(χ2=1.449,P=0.485);组织切片观察8周后大量成纤维细胞长入材料1的人工角膜支架孔隙里。结论纳米HA/PVA多孔复合水凝胶人工角膜具有良好的组织相容性,在宿主兔的角膜内较稳定存在,是一种具有良好临床应用前景的新型人工角膜。

Objective To evaluate the histocompatibility of nano-HA/PVA （nano-hydroxyapatite/polyvinyl alcohol） hydrogel composite keratoprosthesis. Design Animal experiment. Participants Three type of keratoprosthesis： one was made of big-porous nano-HA/ PVA hydrogel; the second one was made of small-porous nano-HA/PVA hydrogel; and the third one,the control one,was made of PVA hydrogel entirely. Methods 21 rabbits were divided into three groups （each group had seven rabbits）. One eye selected randomly from each rabbit from group 1, 2, 3 was implanted the keratoprosthesis type 1, 2, 3, respectively in the corneas through the lamellar kerato- plasty. The host response in the cornea of the rabbit from each group was observed with the slit lamp microscope and histological sections of cornea at 3, 8, and 24 weeks after operation. Main Outcome Measures The score of inflammatory response, the occurrence time and the score of the area of the corneal neovascularization, the stability of the keratoprosthesis, and the histological sections of cornea in each group. Results At 3 weeks after implantation, the mean score of the inflammation responses in group 1, 2, and 3 was 1.29±0.488, 1.43±0.535, and 2.14±0.690 respectively （P=0.027）; at 8 weeks after implantation, the mean score of the area of the the corneal neovascularization in group 1, 2, and 3 was 2.67±0.516, 2.33±0.816, and 1.57±0.535 respectively （P=0.018）; The occurrence time of the corneal neovaseularization in group 1, 2 and 3 was （23.17±1.72） dyas, （24.50±1.05） days, and （29.71±1.60） days respectively （P=-0.000）; the translocation of the keratoprosthesis was appeared in 14.29%, 28.57%, and 42.86% of the cornea in group 1, 2, and 3 respectively （X^2=1.449,P=0.485）;切 After 8 weeks,migration of the keratoeytes and deposition of collagen was detected in the pore of nano-HA/PVA peripheral skirt, which was more remarkable in groupl than in group 2. Conclusion Nano-HA/PVA composite hydrogel keratoprosthesis has been demonstrated a good biocompatibility and could be reserved more stably in the cornea of the host than the one made of PVA hydrogel entirely. It will be optimistic to throw the nano-HA/PVA keratoprosthesis into the clinic use. （Ophthalrrtol CHN, 2011, 20：170-175）