Biocompatibility and Immunotoxicology of the Preclinical Implantation of a Collagen-based Artificial Dermal Regeneration Matrix  

作　　者：WANG Wei ZHANG Lin SUN Lei SHE Zhen Ding TAN Rong Wei NIU Xu Feng 

机构地区：[1]Department of Immunology,School of Basic Medical Sciences,NHC Key Laboratory of Medical Immunology,Peking University,Beijing 100191,China [2]Beijing Advanced Innovation Center for Biomedical Engineering,Key Laboratory for Biomeehanics and Meehanobiology of Ministry of Education,School of Biological Science and Medical Engineering, Beihang University,Beijing 100083,China [3]Shenzhen Lando Biomaterials Company Limtd,Shenzhen 518107,China [4]Research Institute of Beihang University in Shenzhen,Shenzhen 518057,China

出　　处：《Biomedical and Environmental Sciences》2018年第11期829-842,共14页生物医学与环境科学（英文版）

基　　金：supported by the National Natural Science Foundation of China [No.31470915];Shenzhen Science and Technology Project [No.JCYJ20170817140537062];the Fundamental Research Funds for the Central Universities [No.YWF-18-BJ-J-217];the 111 Project [No.B13003]

摘　　要：Objective Graft rejection, with the possibility of a violent immune response, may be severe and life threatening. Our aim was to thoroughly investigate the biocompatibility and immunotoxicology of collagen-based dermal matrix(DM) before assessment in clinical trials. Methods DM was subcutaneously implanted in BALB/c mice in two doses to induce a potential immune response. The spleen and lymph nodes were assessed for shape, cell number, cell phenotype via flow cytometry, cell activation via CCK8 kit, Annexin V kit, and Ki67 immunostaining. Serum samples were used to measure antibody concentration by enzyme-linked immunosorbent assay. Local inflammation was analyzed by histology and immunohistochemistry staining. Data analysis was performed by one-way ANOVA and non-parametric tests. Results Our data illustrate that the spleen and lymph node sizes were similar between the negative control mice and mice implanted with DM. However, in the high-dose DM(DM-H) group, the total cell populations in the spleen and lymph nodes, T cells and B cells in the spleen had slight increases in prophase, and the low-dose DM(DM-L) group did not display gross abnormities. Moreover, DM-H initiated moderate cell activation and proliferation in the early phase post-immunization, whereas DM-L did not. Neither DM-H nor DM-L implantation noticeably increased IgM and IgG serum concentrations. Examination of the local cellular response revealed only benign cell infiltration and TNF-α expression in slides of DM in the early phase. Conclusion Overall, DM-H may have induced a benign temporary acute immune response post-implantation, whereas DM-L had quite low immunogenicity. Thus, this DM can be regarded as a safe product.Objective Graft rejection, with the possibility of a violent immune response, may be severe and life threatening. Our aim was to thoroughly investigate the biocompatibility and immunotoxicology of collagen-based dermal matrix(DM) before assessment in clinical trials. Methods DM was subcutaneously implanted in BALB/c mice in two doses to induce a potential immune response. The spleen and lymph nodes were assessed for shape, cell number, cell phenotype via flow cytometry, cell activation via CCK8 kit, Annexin V kit, and Ki67 immunostaining. Serum samples were used to measure antibody concentration by enzyme-linked immunosorbent assay. Local inflammation was analyzed by histology and immunohistochemistry staining. Data analysis was performed by one-way ANOVA and non-parametric tests. Results Our data illustrate that the spleen and lymph node sizes were similar between the negative control mice and mice implanted with DM. However, in the high-dose DM(DM-H) group, the total cell populations in the spleen and lymph nodes, T cells and B cells in the spleen had slight increases in prophase, and the low-dose DM(DM-L) group did not display gross abnormities. Moreover, DM-H initiated moderate cell activation and proliferation in the early phase post-immunization, whereas DM-L did not. Neither DM-H nor DM-L implantation noticeably increased IgM and IgG serum concentrations. Examination of the local cellular response revealed only benign cell infiltration and TNF-α expression in slides of DM in the early phase. Conclusion Overall, DM-H may have induced a benign temporary acute immune response post-implantation, whereas DM-L had quite low immunogenicity. Thus, this DM can be regarded as a safe product.

关 键 词：Collagen LYMPHOCYTES IMMUNOGENICITY Flow cytometry 

分 类 号：Q[生物学]