Advances in 3D peptide hydrogel models in cancer research

Abstract

In vitro cell culture models on monolayer surfaces (2D) have been widely adapted for identification of chemopreventive food compounds and food safety evaluation. However, the low correlation between 2D models and in vivo animal models has always been a concern; this gap is mainly caused by the lack of a three-dimensional (3D) extracellular microenvironment. In 2D models, cell behaviors and functionalities are altered, resulting in varied responses to external conditions (i.e., antioxidants) and hence leading to low predictability. Peptide hydrogel 3D scaffolding technologies, such as PGmatrix for cell culture, have been recently reported to grow organoid-like spheroids physiologically mimicking the 3D microenvironment that can be used as an in vitro 3D model for investigating cell activities, which is anticipated to improve the prediction rate. Thus, this review focuses on advances in 3D peptide hydrogels aiming to introduce 3D cell culture tools as in vitro 3D models for cancer-related research regarding food safety and nutraceuticals.

Unravelling the antimicrobial activity of peptide hydrogel systems: current and future perspectives

“…This would mirror a similar approach to the use of hydrogels in 3D cell culture and the progress of tumour organoids in cancer research only in a microbial cell setting. 152 Peptide hydrogels could be tailored to serve as gel platforms to study the growth and maturation of planktonic bacteria into the biofilm phenotype. Capturing the early stage transition from planktonic to biofilm form would be especially beneficial.…”

Generation of 3D Spheroids Using a Thiol–Acrylate Hydrogel Scaffold to Study Endocrine Response in ER+ Breast Cancer

“…One of the major limitations of these techniques is weak cell-to-cell interactions resulting in spheroids that poorly mimic in vivo 3D TME. 9 , 23 Furthermore, pellet culture lacks throughput and generates 3D spheroids that are vulnerable to shear stress from centrifugation. 19 3D spheroids generated by spinner culture, magnetic levitation, or liquid overlay techniques exhibit significant heterogeneity in both size and shape.…”

“… 15 , 21 , 24 , 34 − 36 Recent studies suggest that, in the absence of ECM, 3D spheroids exhibit poorer cell-to-cell communication and are physiologically less relevant compared to spheroids generated in ECM-containing systems. 9 , 23 , 37 The droplet-based approach overcomes this limitation by incorporating different types of soft hydrogel materials that can serve as a scaffold for 3D cell culture. Several studies have demonstrated that a hydrogel scaffold provides mechanical forces for cancer cells to support spheroids possessing strong cell-to-cell interactions, extracellular matrix deposition between cells, and gradients in nutrient concentration from the core to the shell of the spheroid.…”

“…Several approaches exist to generate 3D cell culture (herein referred to as 3D spheroids) including pellet culture, hanging droplet arrays, spinner flasks, liquid overlay, and magnetic levitation. − While these approaches can successfully generate 3D spheroids, they suffer from several limitations. One of the major limitations of these techniques is weak cell-to-cell interactions resulting in spheroids that poorly mimic in vivo 3D TME. , Furthermore, pellet culture lacks throughput and generates 3D spheroids that are vulnerable to shear stress from centrifugation . 3D spheroids generated by spinner culture, magnetic levitation, or liquid overlay techniques exhibit significant heterogeneity in both size and shape. , Additionally, magnetic levitation is expensive with an overall low throughput coupled with the fact that the magnetic beads can be toxic at a higher concentration. , Similarly, 3D spheroids generated in hanging drop arrays are difficult to visualize after aggregation, which limits real-time imaging. , Recently, microfluidic devices have become a popular alternative to rapidly generate 3D spheroids.…”

Bacterial Nanocellulose as a Scaffold for In Vitro Cell Migration Assay

“…The reproduction of in vivo conditions for cell growth in 3D requires a gelatinous and flexible matrix, and BNC has adequate characteristics to serve this purpose. The mechanical strength and flexibility of BNC scaffolds compensate for the most common disadvantages of peptide hydrogel matrices used in current 3D cell culture settings [ 20 , 21 ]. Additionally, the BNC scaffolds represent an easily produced low-cost alternative to expensive peptide hydrogel matrices that remain expensive due to difficulties in their production.…”