Azide-modified extracellular matrix as a biomaterial with variably adjustable properties

Dissertation of Silke Keller M. Sc.

The extracellular matrix (ECM) represents the natural microenvironment of the cells within a tissue. It is composed of a complex network of biomolecules like fiber proteins, proteoglycans, and glycosaminoglycans, as well as electrolytes, water, and signaling molecules. The ECM is essential for cellular processes, for instance cell adhesion and –migration, biomechanical stimuli, or the transduction of signals. Due to its unique tissue-specific composition of biomolecules and the resulting high biological activity, the human ECM represents the ideal biomaterial for applications in medical engineering and regenerative medicine.

Extracellular matrix with click functionalities (clickECM). (c)
Extracellular matrix with click functionalities (clickECM).

In order to adjust and modify this exceptional biomaterial according to the varying requirements, scientists of the University of Stuttgart’s Institute of Interfacial Process Engineering and Plasma Technology IGVP in cooperation with the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB developed a functional ECM, which is - even outside of the human body - able to promote cellular behavior and which can customizable be adjusted to the biological scope or to the distinct material. This cell-derived ECM distinguishes itself through the presence of chemical click groups which can afterwards be addressed in a selective and biocompatible chemical reaction with the appropriate binding partner. This click reaction can be used e. g. to bind this so called »clickECM« covalently and therefore stable, to a material surface.

Addition of the modified sugar molecules to the cell culture media. (c)
Addition of the modified sugar molecules to the cell culture media.
Fluorescence microscopic analysis of the clickECM. (c)
Fluorescence microscopic analysis of the clickECM.

To modify the natural ECM with these chemical click groups, the natural metabolism of the cells is used. During cell culture, cells, which were beforehand isolated from a human biopsy, are treated with sugar molecules. Other than conventional sugars, these molecules are modified with the reactive click groups. Through the cell culture media, cells take up this click-functional sugar and use it as a building block for the production of intra- and extracellular molecules.

In order to develop a biomaterial with adaptable properties, the objective is now to investigate and to characterize the clickECM in depth, so that the resulting material can be perfectly adjusted to the distinctive task.

Just like a building set, this versatile biomaterial could in the future display adjustable parameters which could be freely combined in order to achieve the desired functions within the patient’s body. Parameters of such a variable combination could e. g. be the tissue specifity of the ECM, which could be – according to the requirement of the biomaterial – be linked with chemical molecules like hydrogels, growth factors, antibiotics or particular drug carriers.

Silke Keller M. Sc.
 

Silke Keller M. Sc.

Alumni, Ph. D. student, Chemical-Physical Interfaces

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