The group around Dr. Gerald Dräger and Prof. Dr. Andreas Kirschning involved in the cluster of excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy) strongly focus on the development of cardiac tissue formation using polysaccharides as extracellular matrix (ECM). We developed a cross-linking method using the hydrazone formation of modified polysaccharide-aldehydes and hydrazides. This method was applied on various polysaccharides such as hyaluronic acid, alginate, dextran, pullulan, glycogen, cellulose and others.
We successfully applied this cross-linking method on various polysaccharides like alginate and hyaluronic acid to perform several tissue engineering experiments resulting in a novel myocardial tissue based on polysaccharides.
Besides the modification of polysaccharides with respect to later crosslinkage, we produce and use the cyclic pentapeptide RGDfK to enhance the biocompatibility and cell adhesion of our materials. Therefore, we successfully studied the [1,3]-dipolar cycloaddition between an azide-modified RGDfK and a linker-modified polysaccharide.
Our current aim is the development of new crosslinking methods and their application on a library of polysaccharides with different origin. Besides, we are focusing on the synthesis of monomeric model systems of the used polysaccharides. Through those we were able to elucidate the structure of different sideproducts via NMR comparison with the modified polysaccharides.
Another topic of high importance for the REBIRTH group is the mutasynthetic approach to a semisynthetic access to ansamytocin. Ansamitocins are natural products with high cytotoxic properties in the low nanomolar range that are produced by the microorganism A. pretiosum. Therefore, these are very interesting compounds for medical applications. Mutasynthesis in combination with the precursor directed biosynthesis (PDB) and semisynthesis can lead to new natural product derivatives of ansamitocins that can be attached to superparamagnetic nanoparticles by a thermocleavable linker system.
Here, our group developed a method after which the ansamytocin-nanoparticle conjugate can be released via inductive heating procedure. Through the use of an alternating magnetic field a high temperature gets applied on the nanoparticle and hence a retro-Diels-Alder induced that leads to a precise and local release of the desired drug. In our case the derivatives of ansamytocin.
We combined this system with a hyperthermia approach for several studies as alternative to chemotherapy as cancer treatment.
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