Bioactive Bioinks for Micro Cell Manipulation

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, ClexBio can produce tissue mimics featuring structures that are as thin as a single human hair. In the BioMatrix project, ClexBio developed 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 desired cell responses were systematically evaluated. Using the newly developed materials and state-of-the-art microfluidic tools, the consortium has produced encapsulated living human cells in microscopically small hydrogel structures that can be used as building blocks to grow new tissues such as skin or blood vessels in the lab. Notably, 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 in 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. The developed know-how and technologies represent a huge leap towards overcoming the central limitations of current tissue engineering methods and are a valuable asset from biological research to drug development all the way to organ transplantation.

he BioMatrix project formed the foundation for current and future R&D and commercial activities at ClexBio. The project developed a library of modular, bioactive biomaterials for tissue engineering and single-cell analysis applications. This resulted in new IP protecting the newly developed proprietary methods as well as a novel commercial product for the encapsulation of single-cells in physiologically relevant 3D microniches. On top of this, the project developed considerable know-how covering the production, characterization, and bio evaluation of cell-laden microgels that enable the consortium partners to continue developing further innovative solutions within biotechnology and medicine. The developed expertise and methods enable completely new approaches to (i) grow human tissues for transplantation in the lab, and (ii) analyze primary cells such as those taken from a patient biopsy in a physiologically relevant 3D environment. The new tissue engineering methods will have a global impact on both providing novel, cost-effective treatments to currently unmet medical needs and overcoming availability issues of tissue transplants. The single-cell encapsulation technologies have been made commercially available to researchers worldwide and contribute to improved diagnostics, preclinical drug development, and personalized treatment for prevalent conditions such as cancer.

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.