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

• Modified gelatin (gel-MOD) was successfully grafted on sodium alginate.
• The water-soluble copolymers could be cross-linked via three distinct pathways.
• The obtained hydrogels could be reinforced via Ca2+ complexation.
• At 40 °C, the mechanical properties were higher than of cross-linked gelatin.
• The materials displayed similar biological properties as gelatin methacrylamide.

When 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.

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