Thermoresponsive\nSmart Copolymer Coatings Based on\nP(NIPAM-<i>co</i>-HEMA) and P(OEGMA-<i>co</i>-HEMA)\nBrushes for Regenerative Medicine

Abstract

The fabrication of\nmultifunctional, thermoresponsive\nplatforms\nfor regenerative medicine based on polymers that can be easily functionalized\nis one of the most important challenges in modern biomaterials science.\nIn this study, we utilized atom transfer radical polymerization (ATRP)\nto produce two series of novel smart copolymer brush coatings. These\ncoatings were based on copolymerizing 2-hydroxyethyl methacrylate\n(HEMA) with either oligo(ethylene glycol) methyl ether methacrylate\n(OEGMA) or <i>N</i>-isopropylacrylamide (NIPAM). The chemical\ncompositions of the resulting brush coatings, namely, poly(oligo(ethylene\nglycol) methyl ether methacrylate-<i>co</i>-2-hydroxyethyl\nmethacrylate) (P(OEGMA-<i>co</i>-HEMA)) and poly(<i>N</i>-isopropylacrylamide-<i>co</i>-2-hydroxyethyl\nmethacrylate) (P(NIPAM-<i>co</i>-HEMA)), were predicted\nusing reactive ratios of the monomers. These predictions were then\nverified using time-of-flight-secondary ion mass spectrometry (ToF-SIMS)\nand X-ray photoelectron spectroscopy (XPS). The thermoresponsiveness\nof the coatings was examined through water contact angle (CA) measurements\nat different temperatures, revealing a transition driven by lower\ncritical solution temperature (LCST) or upper critical solution temperature\n(UCST) or a vanishing transition. The type of transition observed\ndepended on the chemical composition of the coatings. Furthermore,\nit was demonstrated that the transition temperature of the coatings\ncould be easily adjusted by modifying their composition. The topography\nof the coatings was characterized using atomic force microscopy (AFM).\nTo assess the biocompatibility of the coatings, dermal fibroblast\ncultures were employed, and the results indicated that none of the\ncoatings exhibited cytotoxicity. However, the shape and arrangement\nof the cells were significantly influenced by the chemical structure\nof the coating. Additionally, the viability of the cells was correlated\nwith the wettability and roughness of the coatings, which determined\nthe initial adhesion of the cells. Lastly, the temperature-induced\nchanges in the properties of the fabricated copolymer coatings effectively\ncontrolled cell morphology, adhesion, and spontaneous detachment in\na noninvasive, enzyme-free manner that was confirmed using optical\nmicroscopy.