Abstract

A major hurdle in studying biological systems and administering effective tissue engineered therapies is the lack of suitable cell culture models that replicate the dynamic nature of cell-microenvironment interactions. Advances in the field of surface chemistry and polymer science have allowed researchers to develop novel methodologies to manipulate materials to be extrinsically tunable. Usage of such materials in modeling tissues in vitro has offered valuable insights into numerous cellular processes including motility, invasion, and alterations in cell morphology. Here, we discuss novel techniques devised to more closely mimic cell-tissue interactions and to study cell response to distinct physico-chemical changes in biomaterials, with an emphasis on the manipulation of collagen scaffolds. The benefits and pitfalls associated with using collagen are discussed in the context of strategies proposed to control the engineered microenvironment. Tunable systems such as these offer the ability to alter individual features of the microenvironment in vitro, with the promise that the molecular basis of mechanotransduction in vivo may be laid out in future.

Highlights

  • Tissue structure is one result of the evolutionary pressures imposed to satisfy some of the most complex needs for heat, mass, and fluid transfer within the human body

  • Methods to confine the distribution of extracellular matrix (ECM) ligands and non-adhesive molecules using microcontact printing have enabled the creation of patterns that can prescribe the polarization of cells cultured on 2D surfaces

  • In vivo imaging has revealed cells moving at speeds as high as 3 μm/min; it is expected that the faster modes of cell migration may be best explored in these aligned collagen-substrates

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Summary

Introduction

Tissue structure is one result of the evolutionary pressures imposed to satisfy some of the most complex needs for heat, mass, and fluid transfer within the human body. Due to the complexities involved in studying live tissues in real-time, most research on cell behavior has traditionally focused on two-dimensional (2D) cell culture [1] and more recently, on culturing cells within three-dimensional (3D) matrices [2,3,4] (Figure 1). While the general focus in recent literature has been moving from simple, non-representative systems to more complex systems mimicking real tissues more closely, discrepancies between in-vitro observations and in-vivo behavior continue to be numerous. We examine some of the recent advances in the modulation of cellular microenvironment aimed at mimicking real tissues more closely. Reprinted from [12] with permission from Elsevier; (d) and (e) show the effect of fiber alignment on cell morphology for cells inside 3D collagen matrices with and without imposed alignment respectively. Reprinted from [14] with permission from Elsevier

Engineering the Two Dimensional Landscape
Moving into the Third Dimension
Matrix Tension and Fiber Alignment
Bones to Pick
Conclusions

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