(Iminium)thiolactone-Functional Hyaluronic Acid Hydrogels as Tissue Engineering Scaffolds

• Applicant: Dr. Stefan Mommer
• Subject Area: Polymer Materials ; Biomaterials
• Term: from 2017 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 392874313

A novel materials platform is established which is aimed for the treatment of chronic wounds. Chronic wounds play a major part for which millions of people suffer from and a substantial share of costs comes to burden of the national health insurance systems. They are mostly stuck in an inflammatory stage of the healing process. This inflammatory state hinders the supporting cells to sequester fresh and healthy components of the human extracellular matrix (ECM). The main component is hyaluronic acid, which has become a prominent ingredient for cosmetics or anti-aging products and is also found in the human ECM. Therefore, hyaluronic acid is modified with a chemical functionality (thiolactones). The synthesis of these thiolactones is accomplished, and strategies for the attachment to hyaluronic acid are elaborated. The tholactones bound the the hyaluronic acid backbone offer the possibity to bind peptides and proteins such as binding/growth factors directly to the hyaluronic acid for cell signaling and stimulation of growth. The thiolactones have often been used for the modification of large proteins or enzymes, because they show good reactivity towards the amino groups of respective proteins. In a second reaction step, either guest or host molecules for cucubituril chemistry are reacted with the thiols (released from the thiolactone after ring-opening at the first reaction step). Cucuriturils are macrocyclic molecules, which can host certain positively charged guest molecules to form stable inclusion complexes. The interaction of host and guest proceeds in a non-covalent manner. This reaction strategy will allow (i) the covalent incorporation of growth/binding factors, drug agents and peptides/proteins to the hyaluronic acid and (ii) the non-covalent cross-linking. The latter delivers a material which is extremely malleable and, through shape remodeling, maintains high surface area contact with a surface of interest. Thus, spacial adaption to the individual morphology of the wound is possible. Prior to this final application, the embedding and proliferation of healthy cells in this gel as 3D scaffold is investigated and tuned to favour the thriving and growth of the used cells. In our approach, this material can substitute the defective ECM and promote the embedded cells to remodel and regenerate naturally occuring ECM components. As the healing process is re-boosted, the artificial ECM will be slowly degraded and replaced by the body's own.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Oren Scherman