Role of plasma fibronectin in the foreign body response to biomaterials

Host responses to biomaterials control the biological performance of implanted medical devices. Upon implantation, synthetic materials adsorb biomolecules, which trigger an inflammatory cascade comprising coagulation, leukocyte recruitment/adhesion, and foreign body reaction. The foreign body reaction and ensuing fibrous encapsulation severely limit the in vivo performance of numerous biomedical devices. While it is well established that plasma fibrinogen and secreted cytokines modulate leukocyte recruitment and maturation into foreign body giant cells, mediators of chronic inflammation and fibrous encapsulation of implanted biomaterials remain poorly understood. Using plasma fibronectin (pFN) conditional knock-out mice, we demonstrate that pFN modulates the foreign body response to polyethylene terephthalate disks implanted subcutaneously. Fibrous collagenous capsules were two-fold thicker in mice depleted of pFN compared to controls. In contrast, deletion of pFN did not alter acute leukocyte recruitment to the biomaterial, indicating that pFN modulates chronic fibrotic responses. The number of foreign body giant cells associated with the implant was three times higher in the absence of pFN while macrophage numbers were not different, suggesting that pFN regulates the formation of biomaterial-associated foreign body giant cells. Interestingly, cellular FN (cFN) was present in the capsules of both normal and pFN-depleted mice, suggesting that cFN could not compensate for the loss of pFN. These results implicate pFN in the host response to implanted materials and identify a potential target for therapeutic intervention to enhance the biological performance of biomedical devices. (c) 2007 Elsevier Ltd. All rights reserved.