Role Of Growth Factors In Smooth Muscle Cell Migration In Tissue Engineered Vascular Grafts

Abstract

INTRODUCTION AND OBJECTIVES This study sought to utilize growth factors to promote the migration of smooth muscle cells (SMC) into an electrospun vascular scaffold. The hypothesis was that the use of growth factors would allow for acellular tissue-engineered vascular grafts that are capable of recruiting smooth muscle cellular proliferation and infiltration in situ. METHODS Scaffolds electrospun with poly(ε-caprolactone) (PCL)/collagen polymers were surface modified through the passive adsorption of platelet-derived growth factor with two beta subunits (PDGF-BB) and stromal derived growth factor 1α (SDF-1α) at various concentrations, individually and together. Single-factor studies investigated each factor at concentrations of 100 ng/mL, 250 ng/mL, and 500 ng/mL. Dual-factor studies investigated the combined effects of 100 ng/mL PDGF-BB and 500 ng/mL of SDF-1α. RESULTS Compared to unmodified controls, scaffolds modified with growth factors showed higher rates of smooth muscle cell proliferation. Notably, scaffolds bioconjugated with a concentration of 100 ng/mL PDGF-BB alone and a concentration of 500 ng/mL SDF-1α alone demonstrated the greatest degree of smooth muscle cell proliferation compared to other single-factor concentrations, which confirmed ideal concentrations reported by other studies. A novel finding was that the combination of these growth factors at the aforementioned concentrations showed synergy in the ability to increase the degree of SMC migration into the depth of the electrospun scaffold. CONCLUSIONS This series of experiments verifies that growth factors promote proliferation of SMCs on an electrospun scaffold, and that combining multiple factors can optimize migration of SMCs farther into the thickness of electrospun scaffolds in an in vitro setting. This study sought to utilize growth factors to promote the migration of smooth muscle cells (SMC) into an electrospun vascular scaffold. The hypothesis was that the use of growth factors would allow for acellular tissue-engineered vascular grafts that are capable of recruiting smooth muscle cellular proliferation and infiltration in situ. Scaffolds electrospun with poly(ε-caprolactone) (PCL)/collagen polymers were surface modified through the passive adsorption of platelet-derived growth factor with two beta subunits (PDGF-BB) and stromal derived growth factor 1α (SDF-1α) at various concentrations, individually and together. Single-factor studies investigated each factor at concentrations of 100 ng/mL, 250 ng/mL, and 500 ng/mL. Dual-factor studies investigated the combined effects of 100 ng/mL PDGF-BB and 500 ng/mL of SDF-1α. Compared to unmodified controls, scaffolds modified with growth factors showed higher rates of smooth muscle cell proliferation. Notably, scaffolds bioconjugated with a concentration of 100 ng/mL PDGF-BB alone and a concentration of 500 ng/mL SDF-1α alone demonstrated the greatest degree of smooth muscle cell proliferation compared to other single-factor concentrations, which confirmed ideal concentrations reported by other studies. A novel finding was that the combination of these growth factors at the aforementioned concentrations showed synergy in the ability to increase the degree of SMC migration into the depth of the electrospun scaffold. This series of experiments verifies that growth factors promote proliferation of SMCs on an electrospun scaffold, and that combining multiple factors can optimize migration of SMCs farther into the thickness of electrospun scaffolds in an in vitro setting.