The effect of methacrylic acid in smooth coatings on dTHP1 and HUVEC gene expression

Abstract

Without any external additives such as growth factors, polymer beads containing methacrylic acid (MAA) promoted functional vascularization in vivo leading to faster cutaneous wound healing in diabetic mice and improved skin graft integration in Wistar rats. The aim of this work is to understand this material-driven vascularization by investigating the effect of polymer MAA-content, in the absence of surface roughness, on the behaviour of macrophage-like and endothelial cells. Smooth polymer films containing 20, 30 or 40% MAA or methyl methacrylate as a control copolymerized with isodecyl acrylate, were synthesized to study the effect of MAA content in smooth films, without roughness. Macrophage-like cells (dTHP1) incubated on 40% MAA films for 96 hours increased the expression of the angiogenic genes HIF1α and SDF1α, and of the inflammatory genes IL1β, IL6 and TNFα, while decreasing the expression of osteopontin. Endothelial cells (HUVEC) on 40% MAA films for 96 hours increased the expression of the angiogenic genes MMP9 and CXCR4, and of osteopontin. In dTHP1 cells, principal component analysis established a positive correlation between MAA polymer content, HIF1α expression and the expression of IL6, IL1β and TNFα, suggesting that HIF1α and NF-κB pathway may be involved. It was found that MAA chemistry, without topographical differences, promoted changes in gene expression in macrophage-like and endothelial cells. This effect was more significant above a threshold between 30 to 40% MAA. The amount of MAA in the copolymer likely promoted the cell responses, future work will study the effects of varying MAA content. The 40% MAA coatable material developed in this work may also be of interest as a coating to improve the integration of medical devices.