Biofabrication methods provide great potential to go beyond 2D tissue engineering towards 3D functional tissues and organs for application in regenerative medicine strategies. Despite this promise, the library of materials suitable for fabrication strategies remains relatively small, poorly customizable, and most lack the mechanical complexity of natural extra-cellular matrix (ECM). Towards expanding the materials and strategies for biofabrication, two examples of customized alginate polymers will be presented. Firstly, in order to facilitate 3D bioprinting of large cell laden constructs, we have recently developed a thiol-ene cross-linked alginate hydrogel which can support cell viability, proliferation, and the extrusion based fabrication of 3D structures via UV <i>in situ</i> crosslinking. This hydrogel’s material properties can be rationally tuned and can support the creation of constructs with multifunctional bioactive cues or multiple cell types. Secondly, in order to recapitulate the complex viscoelastic and stress relaxation properties of native ECM, imine-type (dynamic covalent) cross-linked oxidized alginate has also successfully been developed as a bioink platform. The mechanical properties, printability, and self-healing of the resultant hydrogel greatly depend on the nature of the imine type crosslink (oxime is the most elastic while hydrazine is the most viscoelastic) and can be rationally tuned via knowledge of small molecule thermodynamics and kinetics. Furthermore, we have observed significant changes in cell morphology and behavior in this series of hydrogels whereby the most dynamic hydrogels facilitate cell spreading and aggregate formation, while the static hydrogels do not (in 2D and 3D). Both of the presented systems elevate the complexity and tunability of bioinks for 3D printing via simple, yet powerful, crosslinking strategies. Not only does this introduce new materials with biomimietic properties into biofabrication, but also provides some design cues for dynamically cross-linked hydrogel biomaterials.

Development of dynamically cross-linked hydrogels for 3D printing of cell-laden bioinks

2019 Spring National Meeting

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