Abstract

Synthetic 3D extracellular matrices (ECMs) find application in cell studies, regenerative medicine, and drug discovery. While cells cultured in a monolayer may exhibit unnatural behavior and develop very different phenotypes and genotypes than in vivo, great efforts in materials chemistry have been devoted to reproducing in vitro behavior in in vivo cell microenvironments. This requires fine-tuning the biochemical and structural actors in synthetic ECMs. This review will present the fundamentals of the ECM, cover the chemical and structural features of the scaffolds used to generate ECM mimics, discuss the nature of the signaling biomolecules required and exploited to generate bioresponsive cell microenvironments able to induce a specific cell fate, and highlight the synthetic strategies involved in creating functional 3D ECM mimics.

Highlights

  • In vitro cell cultures are widely used in different key biomedical applications such as cellular and organismic biology, drug discovery, or regenerative medicine

  • Cell biology principles, drug activities, cell responses to endogenous and exogenous perturbations, mechanisms involved in cell development,[1] and tissue morphogenesis have been determined by 2D cell culture studies

  • In this Review, we will first present the fundamentals of extracellular matrices (ECMs) and cover the most relevant findings on ECM mimics developed as 3D cell constructs, with emphasis on synthetic strategies to control the morphology, the physical properties, and their functionalization with the different biochemical cues required for cell fate regulation

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Summary

INTRODUCTION

In vitro cell cultures are widely used in different key biomedical applications such as cellular and organismic biology, drug discovery, or regenerative medicine. Despite 2D cell cultures allowing the study of the correlation between cell functions and some components of the microenvironment,[2] such a bidimensional cell environment is obviously unnatural It likely induces different cell behaviors with respect to the natural three-dimensional (3D) microenvironment, lacking most of the interactions occurring in the native 3D tissue. Review involved in disease progressions and the design of efficient cell culture models for biomedical purposes require the use of 3D ECM mimics In this Review, we will first present the fundamentals of ECM and cover the most relevant findings on ECM mimics developed as 3D cell constructs, with emphasis on synthetic strategies to control the morphology, the physical properties, and their functionalization with the different biochemical cues required for cell fate regulation

ECM AND CELL MICROENVIRONMENT
Biochemical and Structural Regulation through
ECM MIMICS
SYNTHETIC STRATEGIES TO MIMIC EXTRACELLULAR MATRICES
Artificial ECMS
CONCLUSION AND FUTURE PERSPECTIVES
■ ACKNOWLEDGMENTS
■ REFERENCES
A 96-Well Microplate Bioreactor Platform Supporting Individual
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