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牛源交联胶原海绵用于止血的免疫反应。

Immune response of bovine sourced cross-linked collagen sponge for hemostasis.

作者信息

Zhang Lin, Niu Xufeng, Sun Lei, She Zhending, Tan Rongwei, Wang Wei

机构信息

1 Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, P. R. China.

2 Shenzhen Lando Biomaterials Co., Ltd, Shenzhen, P. R. China.

出版信息

J Biomater Appl. 2018 Feb;32(7):920-931. doi: 10.1177/0885328217744080. Epub 2017 Dec 4.

Abstract

A comprehensive immunogenicity scheme is proposed to examine immune response of bovine sourced hemostasis collagen sponge to establish foundation for further researches and decrease the incidence of adverse reaction in clinical trials. Compared with negative control group without any implant, spleen and lymph nodes morphology show no apparent swelling in mice with different doses of collagen sponge implants. Immune cells population, especially lymph nodes cells population, is practically coincident with organs. However, splenic cells display slight proliferation in early phase following collagen sponge implantation. Splenic cells apoptosis also demonstrates no significant difference among all groups. T lymphocytes subsets, CD4/CD8 cells ratio, in spleen and lymph nodes are practically normal. Splenic cells Ki67 + proportions do not exhibit significant difference between collagen sponge groups and negative control group. Humoral response is determined by detection of IgG and IgM concentration in serum, not exhibiting remarkable increase with collagen sponge implantation, compared to the drastic increase in positive control group with bovine tendon implantation. Local analysis around implants by hematoxylin-eosin staining discovers slight cell infiltration around collagen sponge. Tumour necrosis factor-α immunostaining indicates slight inflammation in early phase following collagen sponge implantation, but interferon-γ immunostaining is negligible even in positive control group. Collagen sponge, especially in high dose, may have evoked benign immune response in BALB/c mice, but this response is transient. The present evaluation scheme for immune response is integrated and comprehensive, suitable for various biomaterials.

摘要

提出了一种全面的免疫原性方案,以检测牛源止血胶原海绵的免疫反应,为进一步研究奠定基础,并降低临床试验中不良反应的发生率。与未植入任何物质的阴性对照组相比,不同剂量胶原海绵植入小鼠的脾脏和淋巴结形态未见明显肿胀。免疫细胞群体,尤其是淋巴结细胞群体,与器官实际相符。然而,胶原海绵植入后早期脾细胞有轻微增殖。各实验组脾细胞凋亡也无显著差异。脾脏和淋巴结中的T淋巴细胞亚群、CD4/CD8细胞比值基本正常。胶原海绵组与阴性对照组脾细胞Ki67+比例无显著差异。通过检测血清中IgG和IgM浓度来确定体液反应,与牛肌腱植入阳性对照组的急剧增加相比,胶原海绵植入后未表现出显著增加。苏木精-伊红染色对植入物周围进行局部分析,发现胶原海绵周围有轻微细胞浸润。肿瘤坏死因子-α免疫染色显示胶原海绵植入后早期有轻微炎症,但即使在阳性对照组中,干扰素-γ免疫染色也可忽略不计。胶原海绵,尤其是高剂量时,可能在BALB/c小鼠中引发了良性免疫反应,但这种反应是短暂的。目前的免疫反应评估方案是综合全面的,适用于各种生物材料。

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