Cross-linkable alginate-graft-gelatin copolymers for tissue engineering applications

Abstract

a b s t r a c tWhen it comes to failing or injured tissues and organs, patients often end up on waiting lists for tissue or even organ transplantation negatively affecting the patient's quality of life. The multidisciplinary research field of tissue engineering may offer more innovative ways to replace or ideally regenerate failing tissues and organs. A widely used material in this research field is gelatin because of its biocompatibility and interesting hydrogel forming properties. However, at body temperature gelatin's mechanical properties are greatly reduced due to the dissolution of collagen-like triple helices. With the aim to obtain materials that retain their mechanical properties at body temperature, we propose to combine sodium alginate and methacrylamide-modified gelatin (Gel-MOD) in the form of a graft copolymer to obtain a material that closely resembles the extracellular matrix. The obtained materials can be cross-linked via three distinct pathways including cation mediated, temperature mediated or via covalent bond formation after UV irradiation in the presence of a photo-initiator. The current contribution covers the synthesis of the above mentioned alginate-graft-gelatin copolymers and the characterization of the resulting hydrogels. The materials developed are highly hydrophilic, showing high gel fractions and satisfactory mechanical properties. Moreover the attained storage moduli were tunable by divalent cation addition (72-275% increase at 21°C, 42-405% increase at 40°C). One formulation was found to outperform Gel-MOD in terms of mechanical properties at 40°C, thus indicating the proposed strategy can be used to improve the mechanical properties of gelatin-based hydrogels. Moreover, in vitro biocompatibility assays indicated that cell adhesion and proliferation improves with increasing gelatin content. The present paper illustrates that the developed triple cross-linkable materials are suitable cell carriers, promising to be applied for biomedical purposes.

Gelatin- and starch-based hydrogels. Part A: Hydrogel development, characterization and coating

“…Indeed, equilibrium swelling degrees ranging from 660% up to 4100% were observed for the hydrogel samples developed. These results are in good agreement with the results obtained by Graulus et al (2015) for gelatin hydrogels and hydrogels consisting of gelatin and alginate. (Graulus et al, 2015) …”

Development of Gelatin‐Alginate Hydrogels for Burn Wound Treatment

“…Gel‐MA crosslinking was already extensively studied earlier by our research group as well as the optimal amount of Irgacure2959, a biocompatible photo‐initiator, which was determined to be 2 mol% with respect to the amount of methacrylamides introduced . 2 mol% appeared to be sufficient for efficient crosslinking of gel‐MA while preserving its biocompatibility .…”

“…The results of the swelling experiments are expressed as swelling percentage and are calculated according to following equation with W d 0 = weight of dry gel at initial time point and W ht = weight of hydrated gel at time point.…”

“…The gel fraction, that is, the percentage of material that is chemically incorporated, was determined as follows with W de = dry weight after swelling and W d 0 = dry weight before swelling…”

Indirect Solid Freeform Fabrication of an Initiator‐Free Photocrosslinkable Hydrogel Precursor for the Creation of Porous Scaffolds

“…In the field of tissue engineering, it is of crucial importance to generate a 3D environment that mimics the natural extracellular matrix (ECM) to achieve optimal support for cellular adhesion and growth . Ideally, a scaffold, which provides mechanical support, is seeded with cells which then gradually substitute the scaffold material with ECM .…”