Thiol-Ene Alginate Hydrogels as Versatile Bioinks for Bioprinting

Huey Wen Ooi, Carlos Mota, A. Tessa ten Cate, Andrea Calore, Lorenzo Moroni, and Matthew B. Baker

Published: 13/08/2018


Bioprinting is a powerful technique that allows precise and controlled 3D deposition of biomaterials in a predesigned, customizable, and reproducible manner. Cell-laden hydrogel (“bioink”) bioprinting is especially advantageous for tissue engineering applications as multiple cells and biomaterial compositions can be selectively dispensed to create spatially well-defined architectures. Despite this promise, few hydrogel systems are easily available and suitable as bioinks, with even fewer systems allowing for molecular design of mechanical and biological properties. In this study, we report the development of a norbornene functionalized alginate system as a cell-laden bioink for extrusion-based bioprinting, with a rapid UV-induced thiol-ene cross-linking mechanism that avoids acrylate kinetic chain formation. The mechanical and swelling properties of the hydrogels are tunable by varying the concentration, length, and structure of dithiol PEG cross-linkers and can be further modified by postprinting secondary cross-linking with divalent ions such as calcium. The low concentrations of alginate needed (<2 wt %), coupled with their rapid in situ gelation, allow both the maintenance of high cell viability and the ability to fabricate large multilayer or multibioink constructs with identical bioprinting conditions. The modularity of this bioink platform design enables not only the rational design of materials properties but also the gel’s biofunctionality (as shown via RGD attachment) for the expected tissue-engineering application. This modularity enables the creation of multizonal and multicellular constructs utilizing a chemically similar bioink platform. Such tailorable bioink platforms will enable increased complexity in 3D bioprinted constructs.

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