Squarate Cross-Linked Gelatin Hydrogels as Three-Dimensional Scaffolds for Biomedical Applications

Abstract

Hydrogels are useful platforms as three-dimensional (3D) scaffolds for cell culture, drug-release systems, and regenerative medicine applications. Here, we propose a novel chemical cross-linking approach by the use of 3,4-diethoxy-3-cyclobutene-1,2-dione or diethyl squarate for the preparation of 5 and 10% w/v gelatin-based hydrogels. Hydrogels showed good swelling properties, and the 5% gelatin-based hydrogel proved suitable as a 3D cell culture scaffold for the chondrocyte cell line C28/I2. In addition, diffusion properties of different sized molecules inside the hydrogel were determined.

Concentration Selection of Biofriendly Enzyme-Modified Gelatin Hydrogels for Periodontal Bone Regeneration

“…Consistent with the hydrophilicity results, the group 20-5 had the highest degree of swelling (420.940 ± 90.198%), while the 40-10 group had the lowest (233.120 ± 85.269%). Besides, as Stucchi reported, 40 we also observed that the hydrogel with 5% gelatin displayed a significantly higher swelling ratio and suggested that the gelatin concentration could be negatively correlated with the swelling rate.…”

Engineering Hydrogels for Affinity-Based Release of Therapeutic Proteins

“…It retains the same functional groups and amino acid sequences as collagen while exposing additional motifs, such as the RGD (Arg-Gly-Asp) motif, which is often important for cell adhesion . As such, cross-linking methods for gelatin are similar to those for collagen; they can be cross-linked via amino acid side chains with genipin, glutaraldehyde, glyceraldehyde (a nontoxic alternative to glutaraldehyde), dextran dialdehyde, and 3,4-diethoxy-3-cyclobutene-1,2-dione − or through modification with reactive functional groups such as methacryloyl, acrylate, and norbornene groups. An example for the chemical cross-linking of gelatin using EDC/NHS chemistry is the gelatin–chondroitin sulfate gel, which was cross-linked through carboxylate and amino functional groups under acidic conditions at 4 °C .…”

Polysquaramides

“…30 Additionally, tripodal squaramide-based monomers self-assembled into fibrillar supramolecular polymers form self-healing hydrogels under physiological conditions and have been successfully utilized as 3D cell culture media. 29 In addition to their self-assembly ability, squaramides function as effective gelators and covalent probes, as illustrated by their use in forming gelatin-based hydrogels 34 and amine-reactive probes 35 through efficient cross-linking and regioselective reaction of lysine residues with squarates.…”