Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

Abstract

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain.

The Horizon of the Emulsion Particulate Strategy: Engineering Hollow Particles for Biomedical Applications

“…[10] Previous studies have reported the adhesion ligand modified microparticles for cell adsorptions and proliferations, which combined the advantages of both 2D adherent cultures and 3D suspension cultures. Considering the challenging survival rates of the implanted stem cells, it was rather vital to expand the stem cells while maintaining the self-proliferation and multipotency.…”

“…[2] Furthermore, the tunable nanostructures and the distinct properties (e.g., acoustic sensitivity and photomanipulation activity) have paved the ways for high-throughput multiplex assay, noninvasive diagnosis, stimuli-responsive therapy, and tissue regeneration. [10] Through the integration of "yin" and "yang," emulsion particulate technique may shed light on the development of novel hollow structures for improved biomedical applications. [10] Through the integration of "yin" and "yang," emulsion particulate technique may shed light on the development of novel hollow structures for improved biomedical applications.…”

Three‐Dimensional Osteosarcoma Models for Advancing Drug Discovery and Development

“…[24] The new vascular network not only supplies the oxygen and nutrients essential for tumor survival but also provides a route for tumor cell intravasation and extravasation, supporting the tumor development and key events of the metastatic cascade and drug resistance. [9,26,27] The protein portion of the ECM mainly includes collagen, elastin, laminin, and fibronectin, being its spatial distribution dependent of tissue type. [9,26,27] The protein portion of the ECM mainly includes collagen, elastin, laminin, and fibronectin, being its spatial distribution dependent of tissue type.…”

“…[29] This protein network integrates negatively charged polysaccharides produced by the cells which fill the interstitial space by the formation of glycosaminoglycans (GAGs) and proteoglycans, contributing to the compressive resistance of the tissues. [9] Native tissues show mechanical properties that vary from effective elastic moduli of 0.1 kPa in "soft" neural tissues to effective elastic moduli of 20 million times higher in stiff ("hard") bony tissues. The dynamic interaction and structural arrangement of the ECM is closely related with the mechanical stiffness of the tissue and, in turn, with its biological function.…”

“…[9] It means that although intracellular signaling is autonomous, the extracellular microenvironment is responsible for the regulation of important signaling pathways involved in cell survival through the activation of cell membranes receptors (e.g., integrins). In this context, the extracellular matrix (ECM) exhibits a key role depending on its structural features, including the mesh of proteins, stiffness/viscoelasticity, adhesion motifs density, and biophysical properties.…”