The use of hyaluronan to regulate protein adsorption and cell infiltration in nanofibrous scaffolds

Electrospun nanofibers are prepared with mixtures of natural and synthetic polymers that can behave cooperatively to demonstrate combinations of mechanical, structural and biochemical properties for tissue engineering applications. However, the large surface area and inherent small pores of these structures give nanofibrous scaffolds high non-specific protein adsorption and poor cell infiltration. In this study, we developed a protein resistant and porous nanofibrous scaffold composed of hyaluronan (HA), silk fibroin (SF), and polycaprolactone (PCL) blends via one-step emulsion electrospinning. The scaffolds were characterized and evaluated for nanostructures, chemical composition, mechanical properties, hydrophilicity, and protein adsorption. Swelling and degradation studies revealed the formation of oriented pore structures within the body of the scaffolds and increasing the pore size between fibers. Addition of HA component transformed current PCL/SF components into hydrophilic fibers, which caused the suppression of non-specific protein adsorption, resulting in the reduction of fibrosis tissue thickness and macrophages adhesion in vivo. Importantly, HA-based scaffolds significantly enhanced cell infiltration in vitro and tissue ingrowth in vivo. In vitro cultivation of human primary skin fibroblasts on the HA-based scaffolds showed a significant increase in cell proliferation and filopodia protrusions, but decreased in collagen I production. Furthermore, HA and HA-based scaffolds interacted with cell surface receptor CD44 to activate TGF-β1/MMPs signaling pathways that conducive to cell migration. These findings suggest that such an HA-based nanofibrous scaffold resists protein adsorption and enhances cell infiltration, may offer possibilities to overcome the limitations of electrospinning technology.