CPB 697 RESEARCH SEMINAR
Jason P. Hodde,
Graduate Student in Immunology
Department of Veterinary Pathobiology
“Host Response To Collagen Biomaterials: A
Progress Report”
Thursday, October 19, 2006
VPTH 112
3:30 p.m.
ABSTRACT:
Jason P. Hodde†* and Paul W. Snyder†
†Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN, USA
*Cook Biotech Incorporated,
Non-sterile small intestinal submucosa, the base material from which an acellular collagenous biomaterial used in veterinary and human medicine is produced, has previously been reported to stimulate IL-4 production, Th2 development, and the formation of non-complement fixing antibody isotypes in mice following implantation. Histopathology shows that within four weeks following implant, the graft material is fully incorporated by host cells and is undergoing a remodeling response that has been called “site specific”. In this seminar, the ongoing progress of two studies that are underway to assess the inflammatory and immune response to different tissue-derived materials will be presented. In the first, mice were implanted subcutaneously with medical grade Surgisis® and were survived for up to 14 days. Mouse muscle implant (syngeneic) and rat muscle implant (xenogeneic) were used as acceptance and rejection controls, respectively. At necropsy, graft sites were retained and serum collected. The graft interface was evaluated for increases in IL-4 mRNA and IFN- mRNA using real time RT-PCR. Histopathology was performed and the degree and type of inflammation was assessed. In the second study, we compared the murine histopathologic tissue response to implants of Surgisis to another collagen-based implant derived from the renal capsule. Additionally, we examined if the implantation of mucosa tissue or Peyer’s Patch material found in samples of intestinal submucosa would alter the histopathologic tissue response. Groups of six mice were implanted subcutaneously with Surgisis® and other test articles and were survived for up to 28 days. At necropsy, graft sites were retained and serum collected. Serum from the 28-day mice was analyzed for total antibody formation directed against SIS proteins; work to examine relative levels of IgG1, IgG2, IgA and IgM is underway. Histopathology was performed and the degree and type of inflammation was assessed. In the first study, we found local increases in IL-4 mRNA and IFN- mRNA in the rat samples only. Histopathology showed moderate, mixed type inflammation consisting of moderate numbers of neutrophils, macrophages, and lymphocytes in the mouse and Surgisis graft sites. The rat implant sites were characterized by necrotic graft tissue and activated macrophages and foreign body giant cells at the graft periphery. These studies are showing that implantation of mice with Surgisis reveals no evidence of encapsulation or signs of graft rejection, and that, as compared to xenogeneic tissue transplantation, the grafts stimulate only a mild inflammatory and systemic immune response.