Abstract

The development of artificial surfaces which can regulate or trigger specific functions of living cells, and which are capable of inducing in vivo-like cell behaviors under in vitro conditions has been a long-sought goal over the past twenty years. In this work, an alternative, facile and cost-efficient method for mass-producible cellular templates is presented. The proposed methodology consists of a cost-efficient, two-step, all-wet technique capable of producing ZnO-based nanostructures on predefined patterns on a variety of substrates. ZnO—apart from the fact that it is a biocompatible material—was chosen because of its multifunctional nature which has rendered it a versatile material employed in a wide range of applications. Si, Si3N4, emulated microelectrode arrays and conventional glass cover slips were patterned at the micrometer scale and the patterns were filled with ZnO nanostructures. Using HeLa cells, we demonstrated that the fabricated nanotopographical features could promote guided cellular adhesion on the pre-defined micron-scale patterns only through nanomechanical cues without the need for further surface activation or modification. The basic steps of the micro/nanofabrication are presented and the results from the cell adhesion experiments are discussed, showing the potential of the suggested methodology for creating low-cost templates for engineered cellular networks.

Highlights

  • In vitro cellular studies and analysis have become powerful tools in the hands of biology, drug discovery and our understanding of disease prevention, prognosis, and diagnosis

  • The patterned Si wafers were identical to the templates described in detail in [57] which had already been tested with another cell line, namely

  • The ambiguity mainly stemmed from two reasons

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Summary

Introduction

In vitro cellular studies and analysis have become powerful tools in the hands of biology, drug discovery and our understanding of disease prevention, prognosis, and diagnosis. Over the past twenty years, intense research efforts have focused on the development of man-made, artificial surfaces which can regulate or trigger specific functions of living cells, and which are capable of inducing in vivo-like cell behaviors under in vitro conditions. Materials 2016, 9, 256 over predefined pathways Such templates would enhance several biomedical fields covering the entire spectrum from fundamental cellular biology studies to cell-based biosensors for drug development [1,2], tissue engineering, and regenerative medicine [3]. Some characteristic examples which show the vast potential of cellular templates and scaffolds are the following: improving neurophysiological studies through the use of microelectrode arrays (MEAs), where each neuronal cell would be guided on top of a recording/stimulating electrode, while at the same time connected with other neuronal cells sitting on top of a matrix of electrodes, and their interconnectivity could be recorded (this is still an open issue) [4,5,6]; pharmacological studies via cellular networks of controlled topography and interconnectivity [7], and/or co-cultures [8]; cell-based biosensors and cell-on-chip applications, where the cells either play the role of the transducer itself [9,10] or remain the object under investigation [11,12]; cellular self-repair [13] or artificial generation of organs, bone tendons, ligaments, cartilage or even intervertebral discs to replace damaged parts without the need for transplants or in cases where transplants are not possible

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