Abstract

Culture platform surface topography plays an important role in the regulation of biological cell behaviour. Understanding the mechanisms behind the roles of surface topography in cell response are central to many developments in a Lab on a Chip, medical implants and biosensors. In this work, we report on a novel development of a biocompatible conductive hydrogel (CH) made of poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and gelatin with bioimprinted surface features. The bioimprinted CH offers high conductivity, biocompatibility and high replication fidelity suitable for cell culture applications. The bioimprinted conductive hydrogel is developed to investigate biological cells’ response to their morphological footprint and study their growth, adhesion, cell–cell interactions and proliferation as a function of conductivity. Moreover, optimization of the conductive hydrogel mixture plays an important role in achieving high imprinting resolution and conductivity. The reason behind choosing a conducive hydrogel with high resolution surface bioimprints is to improve cell monitoring while mimicking cells’ natural physical environment. Bioimprints which are a 3D replication of cellular morphology have previously been shown to promote cell attachment, proliferation, differentiation and even cell response to drugs. The conductive substrate, on the other hand, enables cell impedance to be measured and monitored, which is indicative of cell viability and spread. Two dimensional profiles of the cross section of a single cell taken via Atomic Force Microscopy (AFM) from the fixed cell on glass, and its replicas on polydimethylsiloxane (PDMS) and conductive hydrogel (CH) show unprecedented replication of cellular features with an average replication fidelity of more than 90%. Furthermore, crosslinking CH films demonstrated a significant increase in electrical conductivity from 10−6 S/cm to 1 S/cm. Conductive bioimprints can provide a suitable platform for biosensing applications and potentially for monitoring implant-tissue reactions in medical devices.

Highlights

  • Over the past two decades, the application of micro fabrication in the field of biology has stimulated interest and experiments on cell growth on topographically modified surfaces

  • We developed a conductive bioimprint technique, a novel 3D replication of cellular morphology onto a conductive hydrogel (CH) matrix based on PEDOT:PSS

  • A soft lithography technique was employed in the process to form a conductive bioimprint that possesses desirable properties for functional cell culture platforms such as good conductivity, biocompatibility, stretchability, high replication resolution, and water resistance [63]

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Summary

Introduction

Over the past two decades, the application of micro fabrication in the field of biology has stimulated interest and experiments on cell growth on topographically modified surfaces. Bioengineering 2021, 8, 204 have previously been reported These studies have been used to understand cell–surface interactions, growth, adhesion, spreading, morphology, proliferation and differentiation of biological cells, as well as cell respond to anticancer drugs [8], as a response to surface topography and substrate material [2,3,4]. As an example, they have shown that cells, which would normally grow randomly on a flat surface in vitro, would align along the surface patterns if grown on parallel lines [2,3,4,9,13,14,15]. The electrical properties of the substrate and how it can be utilised for monitoring cells’ response is something which has not been looked into

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