Short duration gluteraldehyde cross linking of decellularized bovine pericardium improves biological response

Abstract

Gluteraldehyde stabilized bovine pericardium is used for clinical application since 1970s because of its desirable features such as less immunogenicity and acceptable durability. However, a propensity for calcification and long term implant failure is reported because of gluteraldehyde treatment. There is also failure of implant to integrate into host tissue because of its resistance to tissue remodeling. Decellularized bovine pericardium, a potential alternative allows tissue remodeling but it has problems such as immunogenicity and chronic inflammatory response. In this study, decellularized bovine pericardium was subjected to short duration, low concentration gluteraldehyde cross-linking at two levels and its biological response (both in vitro and in vivo) was compared with un-crosslinked decellularized bovine pericardium and fully crosslinked normal bovine pericardium. It was observed that both un-crosslinked and partially crosslinked decellularized bovine pericardium to be non-cytotoxic and it caused significantly less inflammatory cytokine release such as TNF alpha and IL1beta from activated macrophages. Among all groups, short duration 0.2% Gluteraldehyde treated decellularized bovine pericardium showed significantly less antibody response and inflammatory response compared to un-crosslinked decellularized pericardium, short duration 0.6% gluteraldehyde treated decellularized bovine pericardium or completely cross linked bovine pericardium in juvenile rat subcutaneous implantation model. Moreover, short duration 0.2% gluteraldehyde crosslinked decellularized bovine pericardium showed minimum calcification, better host fibroblast incorporation, new collagen deposition and angiogenesis within the implant. These attributes may finally lead to better implant remodeling and sustained implant function during clinical use.