Abstract

Poly(N-isopropylacrylamide) (PNIPAm) is widely used to fabricate cell sheet surfaces for cell culturing, however copolymer and interpenetrated polymer networks based on PNIPAm have been rarely explored in the context of tissue engineering. Many complex and expensive techniques have been employed to produce PNIPAm-based films for cell culturing. Among them, spin coating has demonstrated to be a rapid fabrication process of thin layers with high reproducibility and uniformity. In this study, we introduce an innovative approach to produce anchored smart thin films both thermo- and electro-responsive, with the aim to integrate them in electronic devices and better control or mimic different environments for cells in vitro. Thin films were obtained by spin coating of colloidal solutions made by PNIPAm and PAAc nanogels. Anchoring the films to the substrates was obtained through heat treatment in the presence of dithiol molecules. From analyses carried out with AFM and XPS, the final samples exhibited a flat morphology and high stability to water washing. Viability tests with cells were finally carried out to demonstrate that this approach may represent a promising route to integrate those hydrogels films in electronic platforms for cell culture applications.

Highlights

  • Poly(N-isopropylacrylamide) (PNIPAm) is widely used to fabricate cell sheet surfaces for cell culturing, copolymer and interpenetrated polymer networks based on PNIPAm have been rarely explored in the context of tissue engineering

  • To prepare stimuli-responsive surfaces immobilized on a rigid substrate, we selected the following strategy: synthesis of microgels based on NIPAm and Acrylic acid (AAc); partial substitution of the carboxylic acid groups with vinyl groups; functionalization of glass surfaces with vinyl groups; film deposition spin coating dispersions with the presence of dithiol molecules; promotion of grafting among particles and between particles and glass surface via thermally activated thiol-ene reactions[30]

  • It is known that the insertion of repeating units different from NIPAm may affect the response of the whole system, in particular in the case of random copolymers[33,34]

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Summary

Introduction

Poly(N-isopropylacrylamide) (PNIPAm) is widely used to fabricate cell sheet surfaces for cell culturing, copolymer and interpenetrated polymer networks based on PNIPAm have been rarely explored in the context of tissue engineering. We introduce an innovative approach to produce anchored smart thin films both thermoand electro-responsive, with the aim to integrate them in electronic devices and better control or mimic different environments for cells in vitro. Smart hydrogels are three-dimensional polymer networks that can change their physicochemical properties in response to external stimuli, such as an electrical field and variations in temperature or pH. The great interest for PNIPAm resides in the fact that its LCST value ranges between 32 to 35 °C, close to human body temperature[7,8] This characteristic has been exploited, for instance, in cardiac TE to develop cell-sheet transplantation tissues from patient’s own autologous cells[6]. Elastic modulus can be modified while the mechanical properties of the two networks can be preserved[13,14]

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