3D Cell Culture: Recent Development in Materials with Tunable Stiffness.

Désirée Baruffaldi,Gianluca Palmara,Francesca Frascella,Candido Pirri

doi:10.1021/acsabm.0c01472

Abstract

It is widely accepted that three-dimensional cell culture systems simulate physiological conditions better than traditional 2D systems. Although extracellular matrix components strongly modulate cell behavior, several studies underlined the importance of mechanosensing in the control of different cell functions such as growth, proliferation, differentiation, and migration. Human tissues are characterized by different degrees of stiffness, and various pathologies (e.g., tumor or fibrosis) cause changes in the mechanical properties through the alteration of the extracellular matrix structure. Additionally, these modifications have an impact on disease progression and on therapy response. Hence, the development of platforms whose stiffness could be modulated may improve our knowledge of cell behavior under different mechanical stress stimuli. In this review, we have analyzed the mechanical diversity of healthy and diseased tissues, and we have summarized recently developed materials with a wide range of stiffness.

Highlights

Until about 20 years ago, the earliest attempts to grow cells in three dimensions (3D) showed great promise as this culturing method allowed scientists to better mimic the anatomical structures that are present in the human body
Cells of glioblastoma multiform (GBM) showed differential expression in genes involved in cell and cell−cell adhesion, chemokine and cytokine signaling, nervous system development, and focal adhesion pathways when cultured in 3D scaffolds compared to 2D monolayers.[4]
We reviewed recent developments regarding the synthesis and modification of soft materials that can be used to mimic the mechanical properties of real tissue, thereby serving as an ideal and tunable 3D matrix

Summary

INTRODUCTION

Until about 20 years ago, the earliest attempts to grow cells in three dimensions (3D) showed great promise as this culturing method allowed scientists to better mimic the anatomical structures that are present in the human body. ACS Applied Bio Materials cytoskeletal structure and cell-matrix protein organization, which are linked to important processes such as cell division, migration, and apoptosis.[11] As well depicted in the review of Kechagia and colleagues, integrins on cell membranes act as sensors of mechanical signals derived from ECM. They could form multiprotein plaques in response to an elastic strain leading to cytoskeletal rearrangement, gene transcription, and activation of signaling proteins. Since the fundamental importance of stiffness in tissues and pathology development, in this review, we show how mechanical properties of 3D matrices could be modulated to mimic tissue-specific features

TISSUE STIFFNESS MEASUREMENT

TISSUE MECHANICAL PROPERTIES

CONCLUSIONS AND PERSPECTIVES

Findings

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