Design and Synthesis of Chitosan—Gelatin Hybrid Hydrogels for 3D Printable in vitro Models

Abstract

The development of 3D printable hydrogels based on the crosslinking between chitosan and gelatin is proposed. Chitosan and gelatin were both functionalized with methyl furan groups. Chemical modification was performed by reductive amination with methyl furfural involving the lysine residues of gelatin and the amino groups of chitosan to generate hydrogels with tailored properties. The methyl furan residues present in both polymers were exploited for efficient crosslinking via Diels-Alder ligation with PEG-Star-maleimide under cell-compatible conditions. The obtained chitosan-gelatin hybrid was employed to formulate hydrogels and 3D printable biopolymers and its processability and biocompatibility were preliminarily investigated.

Combined Analytical Approaches to Standardize and Characterize Biomaterials Formulations: Application to Chitosan-Gelatin Cross-Linked Hydrogels

“…Type A gelatin from skin porcine and water-soluble chitosan were employed as starting biopolymers [ 41 , 42 , 43 , 44 ]. These biopolymers were previously investigated in our group for the development of 3D bioprintable GelChiDA hydrogels for 3D cell cultures and tissue engineering purposes [ 15 ]. Briefly, both gelatin and chitosan were functionalized with methylfuran (MF), exploiting, respectively, the amino group of lysine residues of gelatin and the amino group of chitosan by reductive amination.…”

“…Functionalization of Gelatin and Chitosan with methylfuran. Gelatin and chitosan were functionalized with methylfuran as already reported [ 15 ]. Briefly, both polymers were reacted with 5-methylfurfural and NaBH 3 CN performing a reductive amination.…”

“…The combination of different classes of biopolymers, such as proteins and polysaccharides, characterized by different impacts on cells viability and behavior, is a promising approach to build up structures mimicking the complex ECM architectures and role [ 11 , 12 , 13 , 14 ]. To accurately reproduce the ECM properties, new hybrid biomaterials made of natural and/or synthetic polymers are usually designed and synthesized by covalent cross-linking, taking advantage of functional groups already present in the polymer chains or properly introduced [ 15 , 16 , 17 ]. Furthermore, the combination of different polymers increases the system complexity, providing additional motifs for fine control over crucial features for the desired applications [ 18 ].…”

3D Bioprinting of In Vitro Models Using Hydrogel-Based Bioinks

“…Appropriate materials should be carefully chosen for the desired purpose, since each material for the hydrogel bioink has intrinsic characteristics. Blended polymers have been used to complement the characteristics of each polymer material to improve printability and mechanical, physicochemical, and biological properties of the bioink [55]. In particular, photo-cross-linkable polymers (e.g., PEGDA (poly(ethylene glycol) diacrylate) and GELMA (gelatin methacrylate)) are broadly used as solidifiers, and contribute to the solidification of blended bioinks using UV light [56,57].…”

Biomedical Hydrogels Fabricated Using Diels–Alder Crosslinking

“…A hybrid hydrogel, based on gelatin and chitosan to mimic respectively proteic and polysaccharidic components of ECM, was developed and formulated with different methodologies, including 3D bioprinting, to generate 3D scaffolds. [ 42 ] Methyl furan functional groups was introduced on gelatin and chitosan backbones via reductive amination. The obtained methyl furan derivatives were employed in combination with star‐PEG‐maleimideto to fabricate 3D in vitro tumoral brain models.…”