Macrophage Participation in the Degradation and Remodeling of Extracellular Matrix Scaffolds

TLDR

Extracellular matrix scaffolds are widely used to promote tissue remodeling, but the mechanisms by which they influence host responses, particularly the role of macrophages, remain incompletely understood. This study examined whether peripheral blood–derived macrophages drive the degradation of ECM scaffolds. Using a rat body‑wall reconstruction model, the authors compared degradation of CDI‑crosslinked SIS, noncrosslinked SIS, and autologous wall with and without macrophage depletion by clodronate liposomes. Peripheral blood monocytes were essential for early rapid degradation of SIS and autologous wall, whereas CDI‑crosslinked SIS resisted macrophage‑mediated degradation.

Abstract

Biologic scaffolds composed of extracellular matrix (ECM) are widely used to facilitate remodeling and reconstruction of a variety of tissues in both preclinical animal studies and human clinical applications. The mechanisms by which such scaffolds influence the host tissue response are only partially understood, but it is logical that the mononuclear macrophage cell population plays a central role. The present study evaluated the role of macrophages that derive from peripheral blood in the degradation of ECM scaffolds. An established rat body wall reconstruction model was used to evaluate the degradation of carbodiimide (CDI)-crosslinked scaffolds composed of porcine small intestinal submucosa (SIS), noncrosslinked SIS, and autologous body wall. To assess the role of circulating macrophages in the degradation process, the degradation of each scaffold was assessed with and without macrophage depletion caused by administration of clodronate-containing liposomes. Results showed that peripheral blood monocytes are required for the early and rapid degradation of both SIS scaffolds and autologous body wall, and that CDI crosslinked SIS is resistant to macrophage-mediated degradation.