Dual Crosslinked Gelatin Methacryloyl Hydrogels for Photolithography and 3D Printing

Abstract

Gelatin methacryloyl (GelMA) hydrogels have been used in tissue engineering and regenerative medicine because of their biocompatibility, photopatternability, printability, and tunable mechanical and rheological properties. However, low mechanical strength limits their applications in controlled drug release, non-viral gene therapy, and tissue and disease modeling. In this work, a dual crosslinking method for GelMA is introduced. First, photolithography was used to pattern the gels through the crosslinking of methacrylate incorporated amine groups of GelMA. Second, a microbial transglutaminase (mTGase) solution was introduced in order to enzymatically crosslink the photopatterned gels by initiating a chemical reaction between the glutamine and lysine groups of the GelMA hydrogel. The results showed that dual crosslinking improved the stiffness and rheological properties of the hydrogels without affecting cell viability, when compared to single crosslinking with either ultraviolet (UV) exposure or mTGase treatment. Our results also demonstrate that when treated with mTGase, hydrogels show decreased swelling properties and better preservation of photolithographically patterned shapes. Similar effects were observed when three dimensional (3D) printed and photocrosslinked substrates were treated with mTGase. Such dual crosslinking methods can be used to improve the mechanical properties and pattern fidelity of GelMA gels, as well as dynamic control of the stiffness of tissue engineered constructs.

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“…The improved elastic modulus of the GM hydrogels most likely resulted from the increased polymer concentration and crosslinking sites [ 48 ]. These results also demonstrate that mTGase treatment improved the Young’s modulus of the hydrogels, which is in agreement with the results shown in previous studies [ 33 , 49 ]. Moreover, constructing composite hydrogels by mixing dhECM with G and GM allowed us to tune the Young’s modulus values in a wide range from 0.6 kPa to 18.4 kPa.…”

Tunable human myocardium derived decellularized extracellular matrix for 3D bioprinting and cardiac tissue engineering

“…The improved elastic modulus of GM hydrogels is most likely resulting from the increased polymer concentration and crosslinking sites [40]. These results also demonstrate that mTGase treatment improved the Young's modulus of the hydrogels which is in agreement with results shown in previous studies [32,41]. Moreover, constructing composite hydrogels by mixing dhECM with G and GM, allowed us to tune the Young's modulus values in a wide range from 0.6 kPa to 18.4 kPa.…”

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