The applications of the research carried out in this project are found in medicine – in tissue engingeering, reproductive medicine and stem cell therapies. This refers to replacement of cells or tissue e.g. in cancer treatment due to loss of healthy cells hit by cytostatic agents or in brain or spinal cord injury. To produce the tissue or cells requires a medium mimicking the native environment around the cell and this is what this project aims to do. Cellular processes are hence crucially dependent on dynamic receptor-ligand interactions occurring at the interface between the cell membrane and the extracellular matrix (ECM) (J. Robertus, W. R. Browne, B. L. Feringa, Chem. Soc. Rev. 2010, 39, 354 – 378.) Changes in these interactions as a consequence of ECM remodeling, give rise to specific cell signaling and intracellular cascades. These processes are central in the physiology and pathological processes like tissue self-repair and tumorigenesis. As mimics of such dynamic interactions, artificial matrices with reversible display of bioactive ligands have attracted much attention. Surfaces capable of modulating cell-biomaterial interactions are commonly exploited for in-situ cell biology experimentation and in tissue engineering. Current methods to control reversible ligand presentation on biomaterial interfaces mainly rely on surface functionalization with reversible linkers (e.g. noncovalent or reversible covalent interactions) to which the bioactive ligand is tethered (Fig.1). For example, by means of host-guest chemistry, reversible covalent chemistry, molecular assembly or other multiple non-covalent interactions, the integrin-targeted cell adhesive peptide RGD (Arg-Gly-Asp) could be dynamically and reversibly immobilized on the biointerfaces to regulate cell adhesion behavior. These approaches towards simulating the reversible ligand presentation in a biological system have greatly promoted the development of dynamic biointerfaces and a new generation of artificial ECM materials. However, to date, only a few reversible linkage chemistries have been exploited and even fewer that can be geometrically adressed.
The overall objective of this project was to develop a new dynamic and geometrically addressable methodology for biofunctionalization and apply it to reversible cell adhesion and tissue engineering.
