Electrospun Scaffold Fiber Orientation Regulates Endothelial Cell and Platelet Properties Associated with Angiogenesis and Hemocompatibility

Abstract Artificial scaffolds fabricated for tissue engineering and/or regenerative medicine applications typically aim to resemble specific properties of the innate extracellular matrix of a particular tissue. While there have been successes with this approach, it has become apparent that there are certain scaffold properties that are essential for tissue formation. Other, non-essential, properties, however, can aid in tissue formation but are not required for cell growth, maintenance and the formation of viable tissue engineered scaffolds. We aimed to investigate the role of electrospun scaffold topography on endothelial cell and platelet functions related to vascular growth throughout engineered scaffolds. We hypothesized that the growth and compatibility of cells throughout scaffolds would be enhanced as the scaffold topographical organization increased. To test this, we made use of a customized rotational electrospinning apparatus, which can increase the topographical organization of formed scaffolds. Scaffolds fabricated from cellulose acetate, chitosan and/or poly-caprolactone were tested. Our data illustrates that endothelial cells prefer to be cultured on scaffolds with increasing order and larger fiber diameters. In general, platelet activation, adhesion and aggregation responses were not a function of scaffold composition, however, platelets activation and adhesion was generally reduced in the presence of scaffolds, as compared to samples incubated without scaffolds. These results indicate that engineered scaffold properties should be fine-tuned for particular applications and overall, scaffolds may not need to resemble the extracellular matrix in all physical, mechanical and topographical properties to be successful in tissue engineering applications. Statement of Significance When designing engineered tissues, one must consider the physical properties of formed scaffolds as a means to control cell growth characteristics throughout the engineered scaffold. To date, there has been little agreement about which scaffold physical properties are essential for tissue growth. Further, it is essential for growing tissue to include patent vascular networks and here we optimized a method to control the organization of fibers within electrospun scaffolds and promote vascular network growth throughout those scaffolds. Importantly, with increasing fiber organization, scaffolds performed better for vascular tissue engineering applications, in terms of endothelial cell and platelet performance.