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

Wei WANG; Lin ZHANG; Lei SUN; Zhen Ding SHE; Rong Wei TAN; Xu Feng NIU

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

Author: Wei WANG ¹ ; Lin ZHANG ² ; Lei SUN ² ; Zhen Ding SHE ³ ; Rong Wei TAN ³ ; Xu Feng NIU ⁴
Author Information

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 Biomechanics and Mechanobiology 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.
Publication Type:Journal Article
Keywords: Collagen; Flow cytometry; Immunogenicity; Lymphocytes
MeSH: Animals; Biocompatible Materials; adverse effects; analysis; Collagen; adverse effects; immunology; Dermis; immunology; surgery; Female; Flow Cytometry; Immunity, Cellular; Lymph Nodes; immunology; Mice; Mice, Inbred BALB C; Prostheses and Implants; adverse effects; Spleen; immunology
From: Biomedical and Environmental Sciences 2018;31(11):829-842
CountryChina
Language:English
Abstract: 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.