Designing Hydrogels for 3D Cell Culture Using Dynamic Covalent Crosslinking

Abstract

Designing simple biomaterials to replicate the biochemical and mechanical properties of tissues is an ongoing challenge in tissue engineering. For several decades, new biomaterials have been engineered using cytocompatible chemical reactions and spontaneous ligations via click chemistries to generate scaffolds and water swollen polymer networks, known as hydrogels, with tunable properties. However, most of these materials are static in nature, providing only macroscopic tunability of the scaffold mechanics, and do not reflect the dynamic environment of natural extracellular microenvironment. For more complex applications such as organoids or co‐culture systems, there remain opportunities to investigate cells that locally remodel and change the physicochemical properties within the matrices. In this review, advanced biomaterials where dynamic covalent chemistry is used to produce stable 3D cell culture models and high‐resolution constructs for both in vitro and in vivo applications, are discussed. The implications of dynamic covalent chemistry on viscoelastic properties of in vitro models are summarized, case studies in 3D cell culture are critically analyzed, and opportunities to further improve the performance of biomaterials for 3D tissue engineering are discussed.

3D Bioprinting of Multifunctional Dynamic Nanocomposite Bioinks Incorporating Cu‐Doped Mesoporous Bioactive Glass Nanoparticles for Bone Tissue Engineering

“…[ 61 ] As a result, those additional cell adhesion features provided to the dynamically responsive AG network can further promote cell mechanosensing for better spreading. [ 60,62 ]…”

The Intracellular and Extracellular Microenvironment of Tumor Site: The Trigger of Stimuli‐Responsive Drug Delivery Systems

“…In short, the response behavior of the TME can be summarized as bond breakages, hydrophobicity/hydrophilicity transitions, and ion bindings. [ 22 ] Further, the changes in these physical and chemical properties, in turn, realize the transformation of carrier properties, as shown in Figure , including: i) deshielding of polyethylene glycol (PEG); ii) exposure of functional groups; iii) conversion of the surface charge; iv) changes in carrier size/shape; and v) controlled release of drugs. It is this series of transformations that make the TME‐responsive nanoplatform handy in overcoming the barrier.…”

Three-Dimensional Avian Hematopoietic Stem Cell Cultures as a Model for Studying Disease Pathogenesis

“…For the achievement of homogenous localization, cells can be mixed in liquid hydrogels. After the addition of crosslinker or through temperature-induced solidification, the creation of solid hydrogels is achieved ( Rizwan et al, 2021 ). In the case of nanofiber scaffolds, cell localization is highly affected by pore size.…”