Extrusion-Based 3D Printing of Photocurable Hydrogels in Presence of Flavin Mononucleotide for Tissue Engineering

Abstract

3D printing became a widely used technique for tissue engineering applications. This additive technology enables easy fabrication of very complicated structures. However, selection and preparation of initial compositions for 3D printing satisfying high biocompatibility and processability requirements still remains challenging. One of the most promising materials for mimicking of the living tissues are hydrogels possessing properties close to native tissues. In this work, the printability of hydrogels based on hyaluronic acid and poly(ethylene glycol) derivatives dissolved in phosphate buffer saline in presence of flavin mononucleotide as an endogenous photosensitizer has been studied. To produce a hydrogel pattern, the extrusion of photocurable composition has been combined with its simultaneous photoinduced crosslinking under laser irradiation at 450 nm. Cytotoxicity of fabricated films and 3D scaffolds has been tested in vitro using human fibroblasts BJ-5ta.Key words: extrusion; 3D printing; photocurable hydrogel; hyaluronic acid. Hоw to cite: Savelyev A.G., Sochilina A.V., Akasov R.A., Mironov A.V., Semchishen V.A., Generalova A.N., Khaydukov E.V., Popov V.K. Extrusion-based 3D printing of photocurable hydrogels in presence of flavin mononucleotide for tissue engineering. Sovremennye tehnologii v medicine 2018; 10(1): 88, https://doi

Preparing Modified Hyaluronic Acid with Tunable Content of Vinyl Groups for Use in Fabrication of Scaffolds by Photoinduced Crosslinking

“…For DS > 55%, it was impossible to prepare a sample that would retain its shape upon extrusion. We chose mHA with a vinyl group content of 40% as the optimal variant of DS for extrusion; PCCs prepared based on it were used in 3D printing, as described in Savelyev et al [15]. In preparing PCCs, flavin mononucleotide (also known as vitamin B2), which, like HA, is a biocompatible endogenous component of the composition, was used as the photoinitiator.…”

“…These steps were repeated if necessary, i.e., in cases when homogeneous compositions were not formed at the first attempt. The final proportions of the components were: 20 wt % of mHA, 5 wt % of PEGDA, and 0.01 wt % of flavin mononucleotide, which is the same as in a study by Savelyev et al [15]. To prevent premature photocuring, the PCCs were handled only under yellow light.…”

“…Photoinduced crosslinking reactions enable us to create materials with tailored physicochemical properties while preserving their biocompatibility and ability for biodegradation. Scaffolds can be fabricated by micromolding or 3D laser printing [14][15][16][17]; in addition, a construct can be prepared directly in a living body, i.e., without the preliminary in vitro stage [18].…”

Hydrogels: soft matters in photomedicine

“…From the beginning of complex hydrogel preparation, PSs have been used as components for the photogelation of hydrogels and for the photoinitiation 466 of grafting onto films. 159,467 A non-exhaustive list of examples includes eosin Y, 468,469,470,471,472,473 erythrosine B, 474 2,2dimethoxy-2-phenylacetophenone, 475 thioxanthone, 476 benzophenone, 477 riboflavin for localized photodynamic crosslinking, 478,479,480 flavin mononucleotide, 481 camphorquinone, 482 anthraquinone, 483 cinnamate moieties, 484,485 polyoxazoline, 486 anthracene, 487 TiO 2 , 394 and more. A careful selection of the respective PS is necessary if such methods are used for the construction of cell encapsulating systems 488 or for use in 3Dprinting.…”

“…A careful selection of the respective PS is necessary if such methods are used for the construction of cell encapsulating systems 488 or for use in 3Dprinting. 472,481,489 Naturally, standard photocycloaddition reactions can also be applied to cross-link hydrogels, but this typically requires UV irradiation. Recently, Truong et al utilized the 400-500 nm visible light [2+2] photocycloaddition of styrylpyrene to conjugate and cross-link PEG in water to hydrogels.…”