5D Click Printing

Mechanical and functional gradients are reasons for the abundance of functionalities and extraordinary mechanical properties in nature. Mechanical gradients are spatial smooth transitions from mechanically weak to strong structures resulting in materials with remarkable mechanical performance. In case of the in vivo cell environment, the extra-cellular matrix, there are not only mechanical gradients present but also functional gradients, such as an increasing concentration of a bio-active molecule in one dimension. These gradients play an important role in the organization of cells into functional tissues and organs. The imitation of these multidimensional structures by biocompatible and shapeable materials in a straightforward way is a critical challenge that will be addressed in this proposal. The research hypothesis is the development of a novel gradient printing approach, named 5D Click Printing, combining cutting-edge bioprinting technology with state-of-the-art materials and crosslinking chemistry. This will be realized by using functional nanocellulose and polyoxazoline as ink formulations to produce 3D objects with mechanical (+1D) and functional gradients (+1D). The proposed ink formulations are based on functional cellulose nanofibrils and polyoxazolines. These materials were chosen because of their established biocompatibilities, printabilities and the resemblance to the two main components of the extra-cellular matrices, fiber-forming proteins and non-fibrous glycoproteins. The functional groups on the polymers were carefully selected to allow gelation by spontaneous click chemistry, which can be conducted in the presence of living cells. The combination of these new materials and the state-of-the-art gradient printing technology at Queensland University of Technology (QUT) will allow the production of multidimensional objects with gradients in mechanical properties as well as functionality. This interdisciplinary project will be conducted at QUT in Brisbane (Australia), one of the leading centers in 3D printing. The host of this project is Prof. Hutmacher, a world-leading expert in additive manufacturing and the applicant will be further co-supervised by A/Prof. Dargaville with respect to polyoxazoline chemistry. During the return phase to the lab of Prof. Rosenau at University of Natural Resources and Life Sciences Vienna the gained experience and knowledge will be transferred, to establish an advanced gradient printing system in Austria. The 5D Click Printing technology will be further developed to fabricate multidimensional hydrogels with various functionalities. These gels will be used to assess and compare diverse characterization techniques to establish a methodology to visualize gradients in multidimensional objects. In conclusion, the developed technology will be the first straightforward avenue to shaped hydrogels with functional and mechanical gradients. 5D Click Printing will be used to fabricate, bioinspired and sophisticated tissue models for biomedical application, and to produce graded membranes for chromatographic separation of complex biopolymer mixtures.

5D Click Printing: Fabrication of Structures with Mechanical and Functional Gradients Mechanical and functional gradients are reasons for the abundance of functionalities and extraordinary mechanical properties in nature. Mechanical gradients are spatial smooth transitions from mechanically weak to strong structures resulting in materials with remarkable mechanical performance. In case of the in vivo cell environment, the extra-cellular matrix, there are not only mechanical gradients present but also functional gradients, such as an increasing concentration of a bio-active molecule in one dimension. These gradients play an important role in the organization of cells into functional tissues and organs. The imitation of these multidimensional structures by biocompatible and shapeable materials in a straightforward way is a critical challenge that was addressed in this proposal. The research hypothesis was the development of a novel gradient printing approach, named 5D Click Printing, combining cutting-edge bioprinting technology with state-of-the-art materials and crosslinking chemistry. This was realized by using functional nanocellulose, low-viscous gelatin, and polyethylene glycol as ink formulations producing 3D objects with mechanical (+1D) and functional gradients (+1D). Cellulose nanofibrils and gelatin-based inks were chosen because of their established biocompatibilities, printabilities, and the resemblance to the two main components of the extra-cellular matrices, fiber-forming proteins, and non-fibrous glycoproteins. A specific chemical functionalization of these materials enabled controllable gelation by UV crosslinking. For this purpose, a novel and selective production method of cellulose nanofibrils was developed. This method is versatile and allows targeted functionalization of the nanofibers with a variety of functional groups. A combination of these functionalized nanofibers with an established bioink allowed the preparation of hydrogels with functional gradients, in addition, a mechanical gradient was introduced by controlled UV crosslinking. Thus, new and effective methods for the fabrication of multidimensional objects with mechanical and functional gradients were developed. The research project was successfully completed abroad at QUT in Brisbane (Australia), at Julius-Maximilians-University Würzburg (Germany), and during the return phase at the University of Natural Resources and Life Sciences Vienna.