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

Simone Stucchi,Antonino Natalello,Maddalena Collini,Laura Cipolla,Piersandro Pallavicini,Barbara Costa,Alessia D’Aloia,Margaux Bouzin,Michela Ceriani,Roberto Guizzardi,Danilo Colombo

doi:10.1021/acs.langmuir.1c02080

Simone Stucchi, Antonino Natalello + Show 9 more

Open Access

https://doi.org/10.1021/acs.langmuir.1c02080

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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.

Highlights

In recent years, hydrogels have become popular as threedimensional (3D) scaffolds for cell culture providing robust platforms for investigating cell physiology,[1−3] pathology,[4] tissue regeneration,[5,6] drug discovery,[7] and delivery.[8]Depending on the chemistry of the polymeric constituents, and of the cross-linking strategy, hydrogels show different physico-chemical and biological features, accompanied by peculiar advantages and limitations
The cross-linking to the bisamide product was checked by Fourier transform infrared (FTIR) spectroscopy (Figure 2)
diethyl squarate (DES) resulted an effective cross-linking agent for the production of gelatin-based hydrogels; in particular, the 5% gelatin-DES hydrogels resulted in a suitable 3D scaffold for chondrocyte adhesion and spreading

Summary

Introduction

Hydrogels have become popular as threedimensional (3D) scaffolds for cell culture providing robust platforms for investigating cell physiology,[1−3] pathology,[4] tissue regeneration,[5,6] drug discovery,[7] and delivery.[8]. Depending on the chemistry of the polymeric constituents, and of the cross-linking strategy, hydrogels show different physico-chemical and biological features, accompanied by peculiar advantages and limitations. In this framework, the search for new hydrogels and cross-linking strategies is still ongoing, in order to ameliorate their performances toward the desired application. The mechanical properties of gelatin can be improved with different cross-linking agents, that is, exploiting the chemistry of the amino acid side chains through suitable crosslinkers (i.e., glutaraldehyde, genipin, and dextran dialdehyde) and chemistries (thiol−ene, Michael addition, Huisgen cycloaddition, carbodiimide chemistry, epoxy chemistry, etc.).[11−13]

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