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

• Published in: Biomedical and environmental sciences 2018-11, Vol.31 (11), p.829-842
• Main Authors: WANG, Wei, ZHANG, Lin, SUN, Lei, SHE, Zhen Ding, TAN, Rong Wei, NIU, Xu Feng
• Format: Article
• Language: English
• Subjects: Animals; Biocompatible Materials - adverse effects; Biocompatible Materials - analysis; Collagen; Collagen - adverse effects; Collagen - immunology; Dermis - immunology; Dermis - surgery; Female; Flow Cytometry; Immunity, Cellular; Immunogenicity; Lymph Nodes - immunology; Lymphocytes; Mice; Mice, Inbred BALB C; Prostheses and Implants - adverse effects; Spleen - immunology
• ISSN: 0895-3988; 2214-0190
• DOI: 10.3967/bes2018.110

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. 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. 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. 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.