Modular polymer design to regulate phenotype and oxidative response of human coronary artery cells for potential stent coating applications

Abstract

Polymer properties can be tailored by copolymerizing subunits with specific physicochemical characteristics. Vascular stent materials require biocompatibility, mechanical strength, and prevention of restenosis. Here we copolymerized poly(ε-caprolactone) (PCL), poly(ethylene glycol) (PEG), and carboxyl-PCL (cPCL) at varying molar ratios and characterized the resulting material properties. We then performed a short-term evaluation of these polymers for their applicability as potential coronary stent coating materials with two primary human coronary artery cell types: smooth muscle cells (HCASMCs) and endothelial cells (HCAECs). Changes in proliferation and phenotype were dependent upon intracellular reactive oxygen species (ROS) levels, and 4%PEG-96%PCL-0%cPCL was identified as the most appropriate coating material for this application. After three days on this substrate, HCASMCs maintained a healthy contractile phenotype and HCAECs exhibited a physiologically-relevant proliferation rate and a balanced redox state. Other test substrates promoted a pathological, synthetic phenotype in HCASMCs and/or hyperproliferation in HCAECs. Phenotypic changes of HCASMCs appeared to be modulated by Young’s modulus and surface charge of test substrates, indicating a structure-function relationship that can be exploited for intricate control over vascular cell functions. These data indicate that tailored copolymer properties can direct vascular cell behavior and provide insight for further development of biologically instructive stent coating materials.

Combinatorial polymer matrices enhance in vitro maturation of human induced pluripotent stem cell-derived cardiomyocytes

“…However, hydrolytic degradation and modulus did not vary significantly between test matrix materials. These results are consistent with our previous studies [11, 13] and suggest a dominant role of surface chemistry in modulating iPSC-CM phenotype.…”

“…In order to better define the functionally relevant matrix characteristics in vitro , we have employed combinatorial polymer matrices as a synthetic, physicochemically-defined model. [58] A copolymerization technique[11] was used for synthesizing copolymers of different mole percentages of three components known to alter the physicochemical properties which can affect cardiac maturation: PCL was used as the primary component due to its biocompatibility, hydrophophilicity, and slow degradation rate[12]; PEG was used to promote hydrophilicity and water adsorption and to repel proteins and cells[1, 13]; and cPCL was used for increased hydrophilicity and to expose a negative surface charge that was found to reduce the repellent effect of PEG. [14] Since each of these three subunits exhibits distinct material properties, the resulting copolymer can be tailored to modulate cellular responses (Fig.…”

“…[11] The copolymer library contained different mole percentages of three components: hydrophilic poly(ethylene glycol) (PEG), hydrophobic poly(ε-caprolacton) (PCL), and negatively-charged carboxylated-PCL (cPCL). Each copolymer subunit was selected for the specific properties it contributed to the resulting copolymer: PCL is a semi-crystalline, biodegradable, and hydrophobic, as well as being FDA-approved in medical devices[12]; PEG is a biocompatible, hydrophilic, and repellent polymer that reduces protein adsorption and cell attachment through steric exclusion[13, 14]; and cPCL facilitates cell attachment to the scaffold surface by providing a negative charge, effectively counteracting the PEG’s repellant effects. [14] These combinatorial polymers were electrospun to make fiber mesh scaffolds that mimic ECM fiber structure and orientation, and subsequently used as test culture substrates.…”

Uncoupling angiogenesis and inflammation in peripheral artery disease with therapeutic peptide-loaded microgels

“…Our previous studies have showed that this format of combinatorial polymers provides tunable degradation, mechanical, and thermal properties by changing the mole percentages. [20, 32] PEG-PCL was synthesized by ring opening polymerization of ε-caprolactone according to previously published methods. [20, 33] The structure and the number average molecular weight (M n ) calculated by the molar ratio of PEG and PCL was verified by NMR (Fig.…”

Redes epóxi/amina alifáticas com perspectivas para aplicações cardiovasculares. Propriedades biológicas in vitro

“…Filmes poliméricos de alilamina polimerizada via plasma que resultou em boas propriedades adesivas e coesivas ao substrato metálico [11]. (c) Copolímeros de poli(ε-caprolactona) (PCL), poli(etileno glicol) (PEG), e carboxi-PCL (cPCL) que resultaram compatíveis com dois tipos de células de artéria coronária humana [12]. (d) Copolímeros de dextrana-graft-poli(butil-metacrilato) que resultou na formação de uma fina camada polimérica nos stents, que não quebra depois do dispositivo ser submetido à expansão e compressão além de não afetar o crescimento de células endoteliais [13].…”