聚甲基丙烯酸-β-羟乙酯多孔水凝胶义眼台及静电纺丝包裹物的生物相容性能评价

Biocompatibility between poly beta-hydroxyethyl methacrylate/porous hydrogel and electrospinning for wrapping orbital implant

背景:聚甲基丙烯酸-β-羟乙酯水凝胶目前已安全应用于人工角膜和人工晶体的制作,但尚无将其应用于义眼台的研究。用静电纺丝制得的纤维,目前在生物医学领域,包括组织工程支架、表面敷料、药物缓释、医用绷带、呼吸面罩等方面已被广泛应用,但作者尚未查到应用于义眼台包裹物的相关报道。目的:实验制备改性聚甲基丙烯酸-β-羟乙酯水凝胶义眼台和静电纺丝聚氨酯薄膜作为义眼台的包裹物,评价其生物学性能。设计、时间及地点:随机对照动物实验,于2007-04/12在解放军总医院眼科实验室完成。材料:用甲基丙烯酸-β-羟乙酯和甲基丙烯酸甲酯的聚合物单体加入NaCl成孔剂制备多孔水凝胶义眼台;静电纺丝法制备聚氨酯包裹膜;体积分数为75%乙醇浸泡制备同种异体巩膜包裹物。方法:①刺激实验:选取18只Wistar大鼠,随机分为2组,在大鼠脊柱两侧各选4mm×4mm面积的去毛区,一组使用水凝胶义眼台材料,一组使用静电纺丝法聚氨酯薄膜材料,包扎固定4h后除去斑贴物,对实验部位的红斑和水肿反应评分。②流式细胞仪检测实验:另取30只Wistar大鼠随机分为3组,分别行静电纺丝聚氨酯薄膜包裹聚甲基丙烯酸-β-羟乙酯多孔水凝胶义眼台植入术、同种异体巩膜包裹聚甲基丙烯酸-β-羟乙酯多孔水凝胶义眼台植入术、无包裹的单纯多孔水凝胶义眼台植入术。于术前1d、术后1,7,14,21,28d采尾静脉全血检测T淋巴细胞亚群CD4+,CD8+的百分比。主要观察指标:实验部位的红斑和水肿反应,CD4+/CD8+的比值。结果:刺激实验显示两种支架材料均未引起动物皮肤明显刺激,符合标准;流式细胞仪检测实验结果表明与植入前相比,各组外周血T淋巴细胞亚群CD4+/CD8+的比值在术后14,21,28d差异均无显著性意义(P>0.05);眼内植入实验无肉芽肿发生及义眼台排出。结论:静电纺丝聚氨酯薄膜包裹的水凝胶义眼台具有优良的生物相容性。

BACKGROUND： Poly β-hydroxyethyl methacrylate （PHEMA）/hydrogel has been safely used to establish artificial cornea and lens; however, very little studies are related to orbital implant. Fiber produced by electrospinning technique has been widely used in biomedical fields, including tissue engineering scaffold, surface dressing, sustained drug release, medical bandage, and respiratory mask; however, very little reports are correlated to wrapping orbital implant. OBJECTIVE： To establish PHEMNhydrogel combined with polyurethane membrane for wrapping orbital implant, and to study the biological features. DESIGN, TIME AND SETTING： A randomized controlled animal study was performed at the Department of Ophthalmology, the General Hospital of Chinese PLA from April to December 2007. MATERIALS： Ethylene glycol methacrylate compound with methyl methacrylate was mixed with NaCI solution to obtain porous hydrogel orbital implant; polyurethane membrane was established using electrospinning method. A volume fraction of 75% ethanol was used to make homologous sclera wrappage. METHODS： ~ Stimulus test： A total of 18 Wistar rats were randomly divided into two groups. Unhairing area sizing 4 mm× 4 mm was selected from bilateral spine. One area was wrapped with hydrogel, and the other area was wrapped with polyurethane membrane. Four hours later, sticking patch was removed, and erythema and edema were scored. （2） Flow cytometry： An addition of 30 Wistar rats were randomly divided into three groups of which orbital implants were wrapped with polyurethane membrane-coated PHEMA/porous hydrogel, homologous sciera-coated PHEMA/porous hydrogel, and porous hydrogel, respectively. The whole blood was drawn from caudal vein at day 1 before operation, and at clays 1,7, 14, 21, and 28 after operation to detect percentage between T lymphocyte subgroup CD4＋ and CD8＋. MAIN OUTCOME MEASURES： Erythema, edema, and CD4＋/CD8＋. RESULTS： Stimulus test indicated that both materials could not induce stimulus to the skin, which was coincidence with the criteria. Flow cytometry demonstrated that there was no significant difference in CD4＋/D8~ among each group at days 14, 21, and 28 after operation compared to before implantation （P 〉 0.05）. Both granuloma and ocular prosthesis discharge were not observed in the orbital implants. CONCLUSION： The polyurethane membrane-coated hydrogel orbital implant has good histocompatibility, and can be transpranted into the eyes.