Directed Movement of Vascular Smooth Muscle Cells on Gradient-Compliant Hydrogels

TLDR

Current cardiovascular treatments such as angioplasty and stent placement frequently lead to restenosis. Biomaterial coatings that control vascular smooth muscle cell migration are therefore desirable. We developed a novel method to generate substrata with defined mechanical compliance gradients using photopolymerization and patterning. On a 15‑kPa compliant substrate, VSMCs migrated at 53 ± 2.6 μm/h versus 40 ± 3.1 μm/h on 28‑kPa, and they migrated directly from soft to stiff regions on radial‑gradient substrata, accumulating in stiff areas after 24 h, indicating that compliance gradients strongly influence VSMC migration and are a key design parameter for vascular tissue engineering.

Abstract

Current solutions in the treatment of cardiovascular disease include angioplasty and the insertion of stents, but a large number of these cases result in restenosis. Biomaterial coatings that control vascular smooth muscle cell migration are therefore desirable. In this study, we describe a novel method to create substrata with defined gradients in mechanical compliance using photopolymerization and patterning. Cell speed was found to be 53 ± 2.6 μm/h on a substrate with a Young's modulus of 15 kPa compared to 40 ± 3.1 μm/h for a 28 kPa substratum (P < 0.005). We demonstrate that vascular smooth muscle cells undergo direct migration on radial-gradient-compliant substrata from soft to stiff regions of the substrate and that cells accumulate in the stiff regions after 24 h. Our results show that the pattern of the compliance gradient is important and that substrate compliance may be a key design parameter for modulation of cell migration for vascular tissue engineering applications.