Biomimetic Hydrogels in the Study of Cancer Mechanobiology: Overview, Biomedical Applications, and Future Perspectives

Abstract

Hydrogels are biocompatible polymers that are tunable to the system under study, allowing them to be widely used in medicine, bioprinting, tissue engineering, and biomechanics. Hydrogels are used to mimic the three-dimensional microenvironment of tissues, which is essential to understanding cell–cell interactions and intracellular signaling pathways (e.g., proliferation, apoptosis, growth, and survival). Emerging evidence suggests that the malignant properties of cancer cells depend on mechanical cues that arise from changes in their microenvironment. These mechanobiological cues include stiffness, shear stress, and pressure, and have an impact on cancer proliferation and invasion. The hydrogels can be tuned to simulate these mechanobiological tissue properties. Although interest in and research on the biomedical applications of hydrogels has increased in the past 25 years, there is still much to learn about the development of biomimetic hydrogels and their potential applications in biomedical and clinical settings. This review highlights the application of hydrogels in developing pre-clinical cancer models and their potential for translation to human disease with a focus on reviewing the utility of such models in studying glioblastoma progression.

Beyond stiffness: deciphering the role of viscoelasticity in cancer evolution and treatment response

“…Here, the focus is on studies that systematically vary the viscoelasticity of the polymeric matrix to decipher the relationship between ECM viscoelasticity and cancer progression, with the purpose of identifying trends and gaps in the literature. While several reviews have been published in recent years on the impact of matrix viscoelasticity on cancer cell behavior [104,106,107], they do not discuss how different studies characterize the mechanical properties of tumor models. As will be discussed below, this can have a significant impact on the mechanical parameters obtained.…”

A Critical Review on Classified Excipient Sodium-Alginate-Based Hydrogels: Modification, Characterization, and Application in Soft Tissue Engineering

“…During the oxidation of sodium alginate, the number of aldehyde groups increases, and these groups can undergo Schiff's base reaction with amino/hydrazide-modified polymers to generate covalent crosslinks. This crosslinking method can be used to create structurally stable composite hydrogels without the use of an exogenous crosslinking agent or any other crosslinking process [89,90]. Sodium alginate oxide, polyethene glycol, and chitosan can be used together to make an injectable hydrogel that self-crosslinks.…”

The Mechanical and Biological Performance of Photopolymerized Gelatin‐Based Hydrogels as a Function of the Reaction Media

“…In particular, hydrogels, polymeric networks that become hydrated in aqueous media, are being used as artificial matrices trying to mimic the ECM. [4,5] It is nowadays well-known that not only the biochemical features of the ECM but also local physical properties such as stiffness play a key role in the cell biological processes. [6] Hence, it is imperative mimicking not only the biochemistry of the matrix but also the ECM mechanics which has turned out to be a challenging but essential step in this research area.…”