胶原聚合物人体植入材料的生物相容性研究

背景Staar公司将Ⅳ型胶原与水凝胶(HEMA)聚合而成的新型材料Collamer,是研制眼内接触镜的良好材质.国内尚无类似材料.目的评定胶原聚合物为主体的眼内接触镜(intraocularcontactlens,ICL)在动物体内的生物相容性.设计随机对照实验.单位上海生物材料研究测试中心.材料本研究于2000-01/2000-04在上海生物材料研究测试中心完成.细胞株传代48～72h生长旺盛的L-929细胞(小鼠成纤维细胞);白色豚鼠20只,体质量300～500g,1～3月龄,雌雄均可;健康成年新西兰白兔7只,体质量1.7～3.0kg和2.5～3.5kg,雌雄不拘(热原实验,雌兔无孕)(实验动物均由上海实验动物中心提供,为普通级).干预分别应用胶原材料进行以下生物学测试①细胞毒性试验(细胞增殖度法).②致敏试验.③热原试验.④皮下植入试验.实验数据根据标准进行分析和评估.主要观察指标①小鼠成纤维细胞生长和增殖情况.②皮内注射和局部斑贴诱导后,每一观察时间和每一激发部位红斑和水肿反应情况.③家兔由耳缘静脉注入材料浸提液后,该兔体温升高情况.④胶原材料植入家兔皮下后4周材料周围组织反应情况.结果①细胞毒性试验材料组相对增殖度为99%～106%,毒性分级为0～1级.②过敏试验材料组各时段每一激发部位均无红斑和水肿反应,结果评定胶原聚合物皮肤反应0级.③热原试验胶原试品个体升温均在06℃以下,升温总值在1.4℃以下.④皮下植入试验材料组和对照组试样周围均为极少量淋巴细胞浸润,炎症细胞反应为Ⅰ级;纤维囊腔形成评定亦为1级.结论材料生物学测试结果显示胶原聚合物具有高度生物相容性,是设计制造ICL的理想材料.

Biocompatibility research of the collagen-polymer as human implants

BACKGROUND: A new type of materials, Collamer, is polymerized with type V collagen and HEMA by Staar company, which is a good material for the establishment of intraocular contact lens(ICL). There is no similar material in our country.OBJECTIVE: To evaluate the biocompatibility of ICL made mainly by collagen-polymer in animals.DESIGN: A randomized controlled trial.SETTING: Testing Center of Shanghai Institute of Biomaterial.MATERIALS: Our study was conducted in the Testing Center of Shanghai Institute of Biomaterial from January 2000 to April 2000. Cell strain: hearty L-929 cells(fibroblast of mouse) after 48-72 hours of passage; Twenty white guinea pig of either gender aged between 1 month and 3 months with a body mass between 300 g and 500 g; Seven healthy adult New Zealand rabbit of either gender(female rabbits were not required pregnant for pyrogenic reaction test) with a body mass between 1.7 kg and 3.0 kg or between 2.5 kg and 3.5 kg(experimental animals were obtained from Shanghai experimental animal center, ordinary grade).INTERVENTIONS: Collagen was used to perform the following biological tests: ① cytotoxicity test (cell growth rate); ② anaphylaxis test; ③ pyrogenic reactions test; ④ subcutaneous implant test. The data were analyzed and evaluated according to criteria.MAIN OUTCOME MEASURES: ① Growth and proliferation of fibroblast in mice; ② Reactions of erythema and edema of every provocation site and every observatory time after the induction of intradermal injection and local patch test; ③ Increase of body temperature of the rabbit after the injection of the extraction of the material into auricle marginal vein; ④ Reactions around the materials after 4 weeks of collagen implantation in rabbits subcutaneously.RESULTS: ① Cytotoxicity test: relative growth rate of collagen group was 99％ to 106%, and the toxicity grade was level 0 - 1. ② Anaphylaxis test:there was no erythema or edema reaction at every provocation site at each time point of collagen group. The skin reaction to collagen-polymer was level 0. ③ Pyrogenic reactions test: the temperature increased in rabbit was below 0.6 ℃ and the total increase of the temperature was below 1.4 ℃ in rabbits. ④ Subcutaneous implant test: there was very little lymphocyte infiltration around the sample in both collagen group and control group with Level I inflammatory reaction. And the evaluation of the formation of fiber cyst was level I.CONCLUSION: Results of material biological evaluation tests demonstrate that this collagen-polymer has high biocompatibility, and can become an ideal material for ICL.