Effect of chronic inflammation and immune response on regeneration induced by decellularized bovine pericardium

Decellularised tissue produces a variety of host responses ranging from constructive remodeling to scarring on account of its differences in the source of tissue, processing or sterilization methods. In this study, in vivo regeneration induced by decellularised bovine pericardium with or without mild glutaraldehyde crosslinking was studied in relation to its immune and inflammatory response using rat abdominal regeneration model. Mild glutaraldehyde crosslinking was done to subdue inflammatory and immune response without compromising host cell incorporation and graft remodeling. Evaluations were done at both 21 and 90 days. Un-crosslinked decellularised bovine pericardium showed more intense macrophage response predominantly of M2 phenotype at 90 days indicating chronic inflammatory response compared to mildly crosslinked group. This group also showed significant increase in plasma cell and lymphocyte count indicating immune stimulation. Lymphocyte transformation test detected presence of bovine pericardial antigen sensitized lymphocytes at both periods in un-crosslinked group. Lymphocytes from mildly crosslinked group failed to respond in this test at both periods. Significantly higher antibody response was also noted at both periods in un-crosslinked group. However, abdominal wall regeneration was observed only in animals implanted with un-crosslinked decellularised bovine pericardium at 90 days. From the above findings, it is inferred that un-crosslinked decellularised bovine pericardium produced significant chronic inflammatory response at 90 days and stimulated both humoral and cell mediated immune response in comparison to mildly crosslinked decellularised bovine pericardium. Yet this group produced skeletal muscle formation within graft at 90 days.