Gelatin Methacryloyl Hydrogel, from Standardization, Performance, to Biomedical Application

Abstract

Gelatin methacryloyl (GelMA), a photocurable hydrogel, is widely used in 3D culture, particularly in 3D bioprinting, due to its high biocompatibility, tunable physicochemical properties, and excellent formability. However, as the properties and performances of GelMA vary under different synthetic conditions, there is a lack of standardization, leading to conflicting results. In this study, a uniform standard is established to understand and enhance GelMA applications. First, the basic concept of GelMA and the density of the molecular network (DMN) are defined. Second, two properties, degrees of substitution and ratio of solid content, as the main measurable parameters determining the DMN are used. Third, the mechanisms and relationships between DMN and its performance in various applications in terms of porosity, viscosity, formability, mechanical strength, swelling, biodegradation, and cytocompatibility are theoretically explained. The main questions that are answered: what does performance mean, why is it important, how to optimize the basic parameters to improve the performance, and how to characterize it reasonably and accurately? Finally, it is hoped that this knowledge will eliminate the need for researchers to conduct tedious and repetitive pre‐experiments, enable easy communication for achievements between groups under the same standard, and fully explore the potential of the GelMA hydrogel.

Matrix stiffness triggers chemoresistance through elevated autophagy in pancreatic ductal adenocarcinoma

“…GelMA contains abundant arginine-glycine-aspartic acid (RGD) sequences that favor cell attachment. 36 Intriguingly, TCP group exhibited more elongation and spreading form, while for hydrogel group, the cells displayed spheroid-like aggregation and clustering, and the mean diameter of stiff group was larger than that of soft group. The biocompatibility of GelMA hydrogel was determined with a calcein AM/PI cell viability/cytotoxicity assay kit (green: live cell; red: dead cell) (Fig.…”

Hydrogels as Scaffolds in Bone‐Related Tissue Engineering and Regeneration

“…Presently, gelatin methacryloy can be used separately or in combination with other factors to form scaffolds relevant for bone engineering. [102,103] One of such scaffolds was developed by Zhang et al, [56,57] who designed a construct combining deferoxamine@poly(𝜖caprolactone) nanoparticles (DFO@PCL NPs), manganese carbonyl (MnCO) nanosheets, and a polylactide-hydroxyapatite (PLA-HA) with gelatin methacryloyl hydrogel. The idea behind the scaffold was to balance the mechanisms driving the immune system and bone metabolism.…”

Optimization of Gelatin Methacryloyl Hydrogel Properties through an Artificial Neural Network Model

“…Another paper from our group demonstrated that the transfection efficiency of PEGylated and plasmid-encapsulated chitosan nanoparticles could be promoted and that ANN could be an important tool for nanoparticle-mediated gene delivery systems . To date, researchers have investigated the parameters affecting hydrogel stiffness; ,,− the machine-learning-driven prepolymer formulation for GelMA hydrogels required for different biomedical applications is yet to be found. Our study is unique and original for two reasons: (i) the stiffness and mechanical properties of previously published papers have no physiological relevance and so they do not have potential for tissue engineering applications and clinical use, and (ii) for the first time in the literature, we combined an ANN model with our experimental observations to standardize and effectively predict the critical parameters of GelMA hydrogels.…”

“…Protein-based hydrogels, including collagen, fibrin, elastin, and gelatin, have been widely employed in various biomedical applications . Gelatin methacryloyl (GelMA) is the most commonly studied hydrogel in tissue engineering applications − such as 3D culture, , organ-on-a-chip, 3D bioprinting, ,, tissue engineering, , and drug/gene delivery. − GelMA contains cell-binding (Arg-Gly-Asp (RGD)) and matrix-metalloproteinase (MMP)-sensitive degradation sites and may be customized to match many of the key characteristics of the natural extracellular matrix (ECM) …”

“…Das et al demonstrated that matrix stiffness affects the commitment and cellular fate of mesenchymal stem cells . Therefore, the mechanical properties of GelMA hydrogels need to be optimized by altering the cross-linking density for different biomedical applications . By tuning the photo-cross-linking conditions, it is possible to create functional GelMA hydrogels for 3D cell cultures of various tissue types.…”