3D Extracellular Matrix Mimics: Fundamental Concepts and Role of Materials Chemistry to Influence Stem Cell Fate

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.

Tooth-Supporting Hard Tissue Regeneration Using Biopolymeric Material Fabrication Strategies

“…Collagen, as a natural polymer, is the most abundant extracellular matrix (ECM) protein; it is present within mineralized tissues, connective fibrous tissues, and various organs [ 55 , 56 , 57 ] and provides essential structures to support cell–tissue morphogenesis [ 58 , 59 , 60 ]. The interaction between collagen matrices and cells–tissues can produce various signaling molecules to regulate cell adhesion, proliferation, differentiation, and migration [ 61 ] and physiologically promote tissue development [ 58 , 62 ].…”

Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro

“…Scaffolds consisting of different elements of extracellular matrix (ECM) will provide variable stiffness and enable the assessment of the influence on the cellular dissemination and invasion related to metastasis [148]. The alteration of gene expression related to metastasis and invasion usually links to different phases of cancer aggressiveness and relapse which is affected by alteration of microenvironment stiffness.…”

Design and Synthesis of Chitosan—Gelatin Hybrid Hydrogels for 3D Printable in vitro Models

“…3D printing protocols are strongly related to the physical properties of the polymers employed. At the same time, cells embedded in the printable polymers need motifs and functional groups able to mimic biochemical signals and structures present in the natural extracellular matrix (Nicolas et al, 2020 ). The development of new accurately functionalized biopolymers that enable the properties of the final constructs to be tuned is therefore desirable.…”