Development of lipoplex-loaded model surface coatings for the in-situ transfection in the field of bone regeneration

• Applicant: Dr. Christian Wölk
• Subject Area: Pharmacy ; Biomaterials
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 396823779

The German legislation modernised and expanded the definition of medicines for new therapies by including the advanced therapy medicinal products (ATMPs) in the § 4b of the German Medicines Act (AMG). The term ATMPs covers gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineered products, which are defined in the EU guideline 2009/120/EG. An interesting field of research and one application of gene therapy is the DNA-induced bone regeneration in the field of regenerative medicine. In the Western World 5 to 10% of bone fractures show insufficient healing which results in a longer leave of absence and higher costs for the health care system. Hence, numerous strategies in the regenerative medicine focus on initiating fast osteogenesis on artificial scaffolds to stimulate the healing of bone fractures. However, these strategies primary use recombinant proteins to induce osteogenesis, which may result in complex biotechnological manufacturing and therefore high therapy costs.The vision of the project is to produce material films loaded with DNA. Due to gene therapy, the material films induce the local osteogenic differentiation of mesenchymal stem cells which results in rapid bone healing. To realize this vision the proposed project has a number of objectives. First, functionalised material coatings will be developed based on polyelectrolyte multi layers (PEMs). These PEMs are composed of biocompatible polymers and will be loaded with layers of DNA. The incorporated DNA will be complexed by highly effective cationic lipid composites. This lipid encapsulation has protective and transfection enhancing effects. The project focuses on the development of methods to achieve effective loading of the PEMs with lipid/DNA complexes (lipoplexes) and on the intensive characterization using surface sensitive biophysical methods. The second aim is the investigation of the interaction of cells with the functionalized PEMs by using molecular biological methods to investigate cell-film-interactions, viability parameters, effectivity as well as time-scale of the DNA transfer. The third focus is set on the screening of the ability of highly effective PEMs with long-lasting gene transfer to initiate the osteogenic differentiation of cells in in-vitro models.

• DFG Programme: Research Grants