Event Abstract Back to Event Poly-L-arginine based materials as instructive substrates for in vivo synthesis of collagen Hannah C. Bygd1, Anuraag Boddupalli2, Kiva D. Forsmark2 and Kaitlin M. Bratlie1, 2 1 Iowa State University, Materials Science & Engineering, United States 2 Iowa State University, Chemical & Biological Engineering, United States Introduction: The properties of substrates in the extracellular microenvironment affect cells and are key factors in controlling cellular behavior and responses[1]. Implanted biomaterials interact to some extent with surrounding tissues and cells. Ultimately, their in vivo fate depends on the outcome of this interaction. The impact of biomaterials on cells has been widely studied[2],[3]; however, the ability to tune the response of fibroblasts for applications in wound healing and tissue engineering, in particular the substrates ability to alter the alignment of collagen deposition not been explored. Arginine-rich peptides have decreased the presence of myofibroblasts in fibrotic plaques[4]. Furthermore, arginine is metabolized to nitric oxide (NO) through nitric oxide synthase. NO signaling promotes the fibroblast phenotype over myofibroblasts[4].The ability of arginine to prevent myofibroblast differentiation led to developing a library of modified poly-L-arginine (PLR). Materials and Methods: PLR was modified through carbodiimide chemistry. These materials were coated on tissue culture plates and exposed to NIH/3T3 cells. Cell morphology was analyzed through immunocytochemistry (ICC) and vascular endothelial growth factor (VEGF) was assessed through immunosorbant assays. Collagen orientation was also monitored through second harmonic generation microscopy (SHG). These materials were also subcutaneously injected in SKH1-E mice. After 28 days, the tissues were removed and analyzed for VEGF and collagen. Results: An example of the response of NIH/3T3 cells to the modified PLRs is shown in Figure 1. The polarimetry profiles show the orientation of collagen in which the total amount of collagen present at each angle is plotted. Modification 15 is isotropic and represents healthy tissue, while modification 5 and the coverslip result in directional collagen deposition. The red stained cells in the ICC images represent myofibroblasts, which are responsible for aligned collagen. These materials were also implanted in SKH1-E mice and removed after 28 days. The collagen response can be seen in Figure 2. Discussion: These materials were able to alter cell morphology, cytokine production (not shown), and collagen fiber deposition angles by fibroblasts. The materials synthesized here were able to more than triple the amount of VEGF secreted and range from aligned to isotropic collagen orientation. The relationships between material properties and host-response outcomes will be discussed. Healthy tissue is composed of isotropic fibers, while fibrotic and tumor-associated collagen is often well aligned. This alignment results from fibroblasts differentiating into myofibroblasts resulting. Conclusions: This in vivo study was able to draw conclusions relating material properties to fibrotic outcomes, which will vertically impact the field of tissue engineering. These materials demonstrate the potential for rational design to reduce the fibrotic reaction to implants. National Science Foundation Grant No. CBET‐1227867; Roy J. Carver Charitable Trust Grant No. 13-4265