An In Vitro Study of Nano-fiber Polymers for Guided Vascular Regeneration
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An In Vitro Study of Nano-fiber Polymers for Guided Vascular Regeneration Derick C. Miller, Anil Thapa, Karen M. Haberstroh, and Thomas J. Webster Department of Biomedical Engineering, Purdue University West Lafayette, IN 47907-1296 ABSTRACT Biomaterials that successfully integrate into surrounding tissue should match not only the tissue’s mechanical properties, but also the dimensions of the associated nano-structured extracellular matrix (ECM) components. The goal of this research was to use these ideals to develop a synthetic, nano-structured, polymeric biomaterial that has cytocompatible and mechanical behaviors similar to that of natural vascular tissue. In a novel manner, poly-lactic acid/polyglycolic acid (PLGA) (50/50 wt.% mix) and polyurethane were separately synthesized to possess a range of fiber dimensions in the micron and nanometer regime. Preliminary results indicated that decreasing fiber diameter on both PLGA and PU enhanced arterial smooth muscle cell adhesion; specifically, arterial smooth muscle cell adhesion increased 23% when PLGA fiber dimensions decreased from 500 to 50 nm and increased 76% on nano-structured, compared to conventional structured, polyurethane. However, nano-structured PLGA decreased endothelial cell adhesion by 52%, whereas adhesion of these same cells was increased by 50% on polyurethane. For these reasons, the present in vitro study provides the first evidence that polymer fiber dimensions can be used to selectively control cell functions for vascular prosthesis. INTRODUCTION Successful integration of a biomaterial into surrounding tissue can be accomplished by matching not only the tissue’s mechanical properties, but also the dimensions of the native tissue’s extra-cellular matrix (ECM) components. Failure of current vascular graft materials has been attributed, in part, to: (i) compliance mismatch between the vascular graft and the host tissue; (ii) poor cytocompatibility properties and; (iii) combinations of (i) and (ii) [1]. The goal of this research was to determine, for the first time, cellular responses (adhesion, proliferation, etc.) to various polymer fibers; these fibers ranged from conventional (10-15 µm) to biologically-inspired nanometer (50-100 nm) dimensions. MATERIALS AND METHODS Polymer Formulations Poly(lactic-co-glycolic acid) (PLGA) PLGA (50/50 weight % poly(lactic acid)/poly(glycolic acid), Polysciences, Inc.) samples were prepared by dissolving (at 50-60 °C) 0.5 g of PLGA in 8 ml chloroform [2]. This solution was poured into glass petri dishes, allowed to sit overnight, and then transferred to a vacuum (15 mm Hg) oven for 2 days at room temperature. The resulting film was cut into either 0.5 cm x 1 cm or 1 cm x 1 cm strips. The polymer strips were treated in three ways to produce a variety of fiber dimensions: untreated (conventional; fiber dimension ≈ 10 − 15 µm); 0.1 N NaOH for 10 GG3.2.1
minutes (micro-structured; fiber dimension ≈ 1−10 mm); and 10 N NaOH for 1 hour (nanostructured; fiber dimension ≈ 50 − 100nm). Polymer strips were sterilized by
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