壳聚糖/二氧化硅/羟基磷灰石杂化材料的体内反应性研究
Research on the reactivity of chitosan/ SiO2/hydroxyapatite hybrids in vivo
目的 分析壳聚糖/二氧化硅(CS-SiO2)及壳聚糖/二氧化硅/羟基磷灰石(CS-SiO2-HA)杂化材料的体内反应性。 方法 分别将CS-SiO2和CS-SiO2-HA杂化材料植入C57BL/6小鼠腓肠肌内,设置对照组(腓肠肌钝性分离后直接缝合),分别于植入术后14、28、42、56 d摘取包含植入物的腓肠肌,冰冻切片,HE染色及免疫荧光观察材料诱发的局部炎症、肌纤维性坏死与再生。 结果 组织学观察可见,肌内植入初期(14 d),CS-SiO2及CS-SiO2-HA杂化物均诱发炎症细胞渗出,以CS-SiO2-HA组的炎性渗出更为显著。28 d后渗出细胞数量开始下降;56 d时,CS-SiO2组的肌内炎症反应几乎消失,但CS-SiO2-HA仍可见少量渗出。免疫荧光的检测进一步证实,CS-SiO2-HA杂化物较CS-SiO2导致更为严重的肌纤维坏死,所触发的单核/巨噬细胞等炎性渗出范围更广、持续时间久。CS-SiO2及CS-SiO2-HA杂化物移植2月后,肌内炎症基本消失,肌纤维修复完成。 结论 CS-SiO22-HA和CS-SiO2杂化材料在体内均可诱发短期、局部的炎症反应,CS-SiO2的体内相容性优于CS-SiO2-HA杂化物。
Objective To analyze the reactivity of chitosan/ SiO2 (CS-SiO2) and chitosan/SiO2/hydroxyapatite (CS-SiO2-HA) hybrid materials in vivo. Methods CS-SiO2 or CS-SiO2-HA hybrid materials were implanted respectively into the gastrocnemius muscle of C57BL/6 mice and the control group was set up (gastrocnemius blunt dissection after direct suture). Frozen sections of materials containing the gastrocnemius were removed 14, 28, 42, 56 d after implantation, followed HE staining and immunofluorescence to observe local inflammation, muscle fibrous necrosis and regeneration induced by the implanted materials. Results Histological observation showed that in the early stage of intramuscular implantation (14d), CS-SiO2 and CS-SiO2-HA hybrids both induced inflammatory cell infiltration, and the latter was more significant. Number of infiltrated cells began to decrease after 28 d and intramuscular inflammation in the group of CS-SiO2 almost disappeared while there was a small amount of infiltration in CS-SiO2-HA at 56 d. Immunofluorescence further confirmed that CS-SiO2-HA hybrids led to more severe necrosis of muscle fibers, triggered more extensive and prolonged inflammatory infiltration of mononuclear macrophages compared to CS-SiO2. Intramuscular inflammation basically disappeared and the repair of muscle fibers was completed two months after transplantation of CS-SiO2 and CS-SiO2-HA hybrids. Conclusions CS-SiO2-HA and CS-SiO2 hybrid materials can both induce a short-term and local inflammatory reactions while CS-SiO2 has a better compatibility in vivo than that of CS-SiO2-HA hybrids.
Chitosan / SiO2 / Hydroxyapatite / Inflammation / Hybrids
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国家自然科学基金(81572102,81371924);国家重点研发计划(2017YFC1105003)
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