Project: Biofabrication of 3D soft tissue models with a tissue-printing technology and a biosynthetic nanocellulose Cellink.

The aim of this project is to develop a technology platform which will enable biofabrication of 3D living human tissues, “tissue-on-a-plate”, stable for time periods ranging from a few weeks to several months. We focus on biofabrication of soft tissues using bioprinting with a new generation of 3D printer and nanocellulose as an injectable scaffold/cellink. We have selected as the first targets; skin tissue - which is highly desired by the cosmetic industry as a model to evaluate new cosmetic products instead of animal testing; and cartilage tissue which is of interest as an arthritis disease model and also for translation of stem cell technologies for reconstructive surgery. _x000D__x000D_The first phase in our project will be to define the specifications for the new software, the bioprinter and accessories, such as printing nozzles, the control unit, and the cell compatible nanocellulose injectable scaffold/cellink to biofabricate selected 3D soft tissue models (skin and cartilage). The major effort in WP1 will be performed by the Institute for Biomechanics, ETH, Switzerland. This group has access to unique equipment and is able to image soft tissues. Imaging of soft tissue is demanding since there is a lack of contrast which is normally coming from calcium elements in hard tissues. Microarchitecture of soft human tissues will be determined by imaging and developing a generalized model of 3D architecture skin and cartilage. The ETH group will perform imaging from several donors and build up the library of microarchitecture of human soft tissue and develop a universal model of skin and cartilage tissues. Later, these models will be converted from imaging files such as dicom into stl files which can control the motion of the bioprinter. This library will contain 3D scaffold architectures which include pore size and porosity but also mechanical properties. All this will affect cell migration, attachment, proliferation and finally differentiation. In addition the inherent mechanical properties play an important role in controlling cellular fate processes. The biomaterial that constitutes the scaffold also plays a crucial role in the differentiation process of stem cells. Biosynthetic Nanocellulose is a biomaterial with several FDA approvals for clinical applications, and is produced by bacteria giving a unique combination of biocompatibility and biomechanics. This nano-biomaterial has been shown to be cell friendly and is very attractive as a scaffold. _x000D__x000D_The second task in this project is development (WP2), of firstly the nanocellulose suspensions with optimal rheological properties to be used as cellink in the 3D printer, and secondly, the bioprinter. This first task will be performed by Swedish SME Advanced Polymer Technology AB. Cellink development will include study of the effect of nanofiber dimensions and concentration and shear stress on the viscosity of nanocellulose suspension. Advanced Polymer Technology AB has access to medical grade biosynthetic nanocellulose which is critical to guarantee biocompatibility. The optimal composition will be forwarded to Swiss SME, regenHU which produces bioprinters. Bioprinter development will be performed in this EUROSTARS project by regenHU, and will include development of the printer nozzle and printing head controlling functions to convert nanocellulose Cellink into 3D scaffolds with the microarchitecture defined by the model developed in WP1. In this task special attention will be paid to spatial control of the nanocellulose suspension deposition which will be affected by the rheological properties of the nanocellulose Cellink. The bioprinting protocols developed by regenHU will include options for cell deposition making it possible to biofabricate skin and cartilage tissue in one step. An alternative procedure is to biofabricate 3D scaffolds which are later seeded with cells. _x000D__x000D_In WP3, 3D nanocellulose scaffolds with defined microarchitecture will be evaluated with regards to cytotoxicity, biocompatibility and mechanical integrity by BBV Laboratory at Chalmers in Sweden. After approval of the 3D scaffold structures all Ps, in WP4, will assemble and introduce to market the package which is: Bioprinter with cell- and bio-compatible cellink for use with a software incorporating a suite of soft tissue models with defined architecture._x000D__x000D_The innovation in this collaborative project is to develop nanocellulose as an injectable scaffold/cellink in a consortium involving RegenHU, Advanced Polymer Technology AB, ETH, and Chalmers; as well as to further develop the bioprinter and accessories for material deposition. Together this Swiss-Swedish R&D consortium will provide a solution for reproducible biofabrication of 3D tissue research and diagnostics. In the later phase of this Eurostars project the application will be evaluated with select customers within cosmetic industry and academic institutions. _x000D_

Acronym CELLINK (Reference Number: 8355)
Duration 01/10/2013 - 31/03/2016
Project Topic Development of a technology platform to biofabricate (bioprint) 3D soft tissues (skin, and cartilage) with defined microarchitecture and structural integrity using Nanocellulose as a cell compatible, injectable scaffold/ cellink and _x000D_ regenHU´s bioprinter.
Network Eurostars
Call Eurostars Cut-Off 10

Project partner

Number Name Role Country
4 Chalmers University of Technology Partner Sweden
4 Advanced Polymer Technology AB Partner Sweden
4 ETH Zurich Partner Switzerland
4 regenHU Ltd Coordinator Switzerland