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NANO2021-Nanoteknologi og nye materiale

Bioactive Bioinks for Micro Cell Manipulation

Alternative title: Innkapsling av Celler i Bioaktive Strukturer på Mikroskala

Awarded: NOK 6.3 mill.

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2020 - 2022


Every day patients die because they do not get a life-saving organ transplant or medical treatment in time. Many lives could be saved if human tissues and organs could be recreated in the lab. Considerable technological advancements like 3D bioprinting have brought this vision within arm's reach. These technologies aim at building artificial tissue and organ structures. These structures are made out of a matrix of jelly-like hydrogel materials containing living human cells. However, the currently existing methods fail to fabricate tissues with real biological function due to the lack of methods to build cell-laden, living 3D structures at the required size scale of only a few micrometers, which is required to reproduce complex architectural features of functional organs like blood capillaries. The innovative CLEX technology has pushed this boundary by enabling the fabrication of defined hydrogel microstructures in the presence of living cells. Using advanced microfabrication devices combined with the CLEX hydrogel technology, CLEX BIO can produce tissue mimics featuring structures that are as thin as a single human hair. Within this project, CLEX BIO is developing a new generation of advanced CLEX materials and microfabrication methods together with its partners at NTNU and SINTEF. Different strategies to modify the CLEX hydrogels to stimulate deliberate biological responses are systematically evaluated. Additionally, the company has started to produce and test prototypes of new tools to fabricate cellularized microstructures that will form the essential building blocks to create living human tissues in the lab. Notably, to date, the BioMatrix project has facilitated the development of two entirely new methods and one new commercial product. The newly developed methods make it possible to grow strong and healthy human tissues with or without blood vessels with unprecedented efficiency and nearly any shape. The commercial launch of the CYTRIX hydrogel kit together with UK-based microfluidic expert Sphere Fluidics, on the other hand, enables researchers around the world to harness CLEX for studying individual cells in 3D microenvironments that mimic the natural cell environment. If the project is successful, the results will allow overcoming the central limitations of current tissue engineering technologies and be an invaluable asset from biological research to drug development all the way to organ transplantation.

CLEX BIO alongside research partners are developing innovative bioactive hydrogel materials toward tissue engineering and single-cell analysis applications. The study and manipulation of cells in three-dimensional environments is a crucial aspect of understanding cell physiology, building improved laboratory models and engineering tissues for clinical applications. Yet, attempts to engineer cellular tissue structures are presently hampered by a lack of biomaterials that can support normal cell physiology while allowing structuring into tissue-like architectures. The patented technology of CLEX BIO allows structuring of materials using microfluidic technology for encapsulation of live cells at micrometre resolution, addressing important challenges and limitations of currently available solutions. The objective of the BioMatrix project is to produce and characterise functionalised alginates in the development of generic cell- and tissue-stimulating "bioinks", that can be structurally tailored towards specific applications. The functionalisation aims at providing attachment points for cell interaction and motility within the material, and tuneable mechanical properties and biodegradability of the materials. New microfluidic devices will be developed for implementation of these bioinks with the CLEX technology to allow mild and precisely controlled encapsulation of live cells in microfibres and microspheres in processes with high throughput and reproducibility. Lastly, the project will assess cell proliferation and tissue development in vital proof-of-concept studies for benchmarking the efficacy of the bioinks and the micro-structuring technology. In addition to stimulating the commercial development and research activities of CLEX BIO, the project will address central knowledge gaps and contribute novel materials and methodology for biomaterial-based cell encapsulation and tissue engineering.


NANO2021-Nanoteknologi og nye materiale