349706 SH3-Domain Affinity Based Fibronectin Biomaterials for Wound Healing
349706 SH3-Domain Affinity Based Fibronectin Biomaterials for Wound Healing
Monday, November 4, 2013
Grand Ballroom B (Hilton)
A major problem in the healing of large wounds is the loss of the extracellular matrix (ECM) which serves as a scaffold on which cells and tissues grow. Components of the ECM are secreted by healthy epithelial tissue, but after its loss in a wound these cells are no longer present to secrete the proteins and other structural components of the extracellular matrix. Fibronectin (FN) is a protein in the extracellular matrix that interacts with integrin receptors on the surface of epithelial cells and provides cellular signals for migration, differentiation, and growth. To that end, biomaterials have been synthesized that contain fibronectin or RGD cell binding domains from fibronectin to help create the conditions necessary for cell migration and growth in wounds. Previously, biomaterials have been synthesized with either covalently immobilized fibronectin or adsorbed fibronectin. Of these, immobilized fibronectin has been shown to be more effective at promoting cell adhesion due to its increased retention over the adsorbed case; however, the immobilized protein's geometry lacks the ability to be reorganized by epithelial cells during the healing process. We propose a protein system based on the Src homology 3 (SH3) domain affinity interaction that allows for increased retention of fibronectin over the adsorbed case, while still preserving the ability of epithelial cells to modify the local protein geometry. We have shown in cell-free studies that this SH3 domain interaction is effective at leading to increased retention over adsorbed fibronectin, but below that of covalently immobilized fibronectin. Fibroblasts seeded on surfaces utilizing the SH3 interaction exhibit significantly higher motility and spreading than on surfaces containing adsorbed or covalently bound fibronectin. These results imply that biomaterials utilizing this interaction may assist in the wound healing process.
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