Role of plasma fibronectin in the foreign body response to biomaterials

Abstract

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 conditional knock-out mice, we demonstrate that plasma fibronectin modulates the foreign body response to polyethylene terephthalate discs implanted subcutaneously. Fibrous collagenous capsules were two-fold thicker in mice depleted of plasma fibronectin compared to controls. In contrast, deletion of plasma fibronectin did not alter acute leukocyte recruitment to the biomaterial, indicating that plasma fibronectin modulates chronic fibrotic responses. The number of foreign body giant cells associated with the implant was three times higher in the absence of plasma fibronectin while macrophage numbers were not different, suggesting that plasma fibronectin regulates the formation of biomaterial-associated foreign body giant cells. Interestingly, cellular fibronectin was present in the capsules of both normal and plasma fibronectin-depleted mice, suggesting that cellular fibronectin could not compensate for the loss of plasma fibronectin. These results implicate plasma fibronectin in the host response to implanted materials and identify a potential target for therapeutic intervention to enhance the biological performance of biomedical devices.

Effects Of Gelatine-Coated Vascular Grafts On Human Neutrophils

“…Again, experiments revealed that PMN-related responses are altered and bacterial coupling sites are masked or presented (3,4,12,34,38,43,44). In the presented study, plasma coating influenced the PMN-related receptor expression, which was mainly caused by a delamination of gelatine and primary effect of the material.…”

“…The augmented shedding in native polyester can be explained by an improved contact to the material due to fibrinogen. Several groups have elucidated the specific binding sites (21,43,44). Native polyester induced also greater magnitudes fort he mediators IL-8 and LTB 4 than gelatine-coated polyester did.…”

Mesenchymal stem cell transplantation to promote bone healing

“…The fibrous response to implanted materials involves binding of fibronectin to integrins on the cell surface. 20 In our previous work that examined integrin expression and function in skeletal cells, it was shown that both were disrupted in FGFR3 À/À MSC grown ex vivo 21 and contributed to a fibrous peri-implant response in FGFR3…”

NCO-sP(EO-stat-PO) surface coatings preserve biochemical properties of RGD peptides

“…interactions with plasma fibronectin that do not necessarily contribute to an optimal bone ingrowth. They may instead lead to negative effects like foreign body reaction and fibrotic processes (5,6). Specific tuning of the material surface can be used to minimize these non-specific effects and may rely on the molecular mechanisms of cell adhesion mainly mediated by integrins which provide selective interactions with the proteins of the extracellular matrix (7).…”