Macrophage-mediated degradation of crosslinked collagen scaffolds

Biological scaffolds used in tissue engineering are incorporated in vivo by a process of cellular in-growth, followed by host-mediated degradation and replacement of these scaffolds, in which phagocytic cells from the monocyte/macrophage cell lineage play a key role. The chemical degradation of scaffolds with collagenases is well established, but to date this has not been correlated with an in vitro model of cell mediated scaffold degradation. RAW264.7, a murine monocyte/macrophage cell line, was cultured on collagen scaffolds crosslinked either by dehydrothermal treatment (DHT) or by carbodiimide (EDC). These cells attached to collagen scaffolds, proliferated and exhibited macrophage aggregation to form giant cells. Crosslinking the scaffolds by either DHT or EDC increased the resistance of the scaffold to degradation by macrophages. Increasing the amount of crosslinking in the scaffold made them more resistant to degradation by collagenase. However, while EDC increased the scaffolds’ thermal and mechanical properties and decreased the swelling ratio, DHT increased the mechanical properties, but decreased the denaturation temperature and swelling ratio. Altering the scaffold properties by crosslinking affects the rate of degradation by macrophages, and this is correlated with chemical degradation (r = 0.658, p < 0.01). This will help in the design of scaffolds with task-specific profiles for use in tissue engineering.