The host response to endotoxin-contaminated dermal matrix

Biologic scaffold materials composed of extracellular matrix (ECM) have been shown to promote the formation of site-specific, functional, host tissue following placement in a number of preclinical and clinical studies. Endotoxin contamination of biomaterials is thought to result in deleterious immune responses that may affect the remodeling outcome when present in significant quantities. However, the exact amount of endotoxin contamination within or upon an ECM-based biologic scaffold that is required to elicit adverse effects in recipients is currently unknown. The present study examined the in vitro and in vivo effects of endotoxin contamination within an ECM scaffold derived from porcine dermis upon the host immune response and the downstream ability of the scaffold material to promote constructive tissue remodeling. Test articles with endotoxin values that exceed the current U.S. Food and Drug Administration (FDA) limit had similar or decreased immune responses both in vitro and in vivo when compared with devices that were below the current FDA limit. Dermal matrices spiked with large doses of endotoxin (100 ng/mL), equivalent to 10-20 times the FDA limit, elicited a robust immune response in vitro. However, by 35 days postimplantation, no difference in tissue remodeling was detected, regardless of the amount of endotoxin present within the material. These results suggest that current endotoxin standards may fall well below levels that induce an adverse acute proinflammatory response and associated long-term deleterious effects upon tissue remodeling outcomes.