TRR 67:  Functional Biomaterials for Controlling Healing Processes in Bone und Skin - From Material Science to Clinical Application

• Subject Area: Biology ; Chemistry ; Materials Science and Engineering ; Medicine
• Term: from 2009 to 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 59307082

The demographic trends in Germany and other industrialized nations result in a considerable increase in patients with bone defects and chronic wounds. This requires the development of novel functional biomaterials, which improve bone and skin regeneration in an aging, multimorbid population. New knowledge about the role of the extracellular matrix (ECM) for the regeneration of tissues opens new opportunities for the design of innovative biomaterials. The structure and composition of ECM significantly influences cellular differentiation and function and the healing of tissues. The aim of the TRR 67 is to develop and investigate novel functional biomaterials based on artificial (a) ECM. Essential functional components of these materials are glycosaminoglycan derivatives and proteoglycan analogues in combination with structural proteins or synthetic carrier substances.In the current second funding period of the TRR 67, we demonstrated that certain aECM -based biomaterials facilitate healing processes in bone and skin; moreover the underlying molecular mechanisms could be identified. In the third funding period, the objective will be taken to a more complex level, by endowing the biomaterials with several functionalities in order to adapt them to the specific requirements of the different phases of regeneration in bone and skin. For example, biomaterials will be designed which combine anti-inflammatory, wound healing promoting with antibacterial or good adhesive properties. Furthermore, we shall investigate the molecular mechanisms by which these multifunctional biomaterials influence regenerative processes within tissues. In order to strengthen the translational aspect, the multifunctional aECM-based biomaterials will be incorporated in implant coatings, wound dressings, or as carrier systems for cell therapeutics, and evaluated in relevant preclinical models with impaired bone or skin regeneration. Subsequently a validation on cell or tissue samples from patients with restricted bone or skin regeneration is planned; however we do not apply for funding of clinical studies at this stage. The long-term goal is to individualize the aECM-based biomaterials for certain patient populations (e.g. osteoporosis, diabetes).

• DFG Programme: CRC/Transregios

Completed projects

• A01 - Three-dimensional aEZM polymer hybrid matrices for the characterization of artificial ECM components (Project Heads Hacker, Michael ;  Schulz-Siegmund, Michaela )
• A02 - Synthesis and characterization of ECM-specific polysaccharides (Project Heads Schiller, Jürgen ;  Schnabelrauch, Matthias )
• A03 - Development and characterization of artificial extracellular matrices based on collagen and glycosaminoglycan derivatives (Project Heads Hintze, Vera ;  Scharnweber, Dieter ;  Worch, Hartmut )
• A04 - Chemical modification of proteins for the characterization of matrix-protein interactions (Project Head Beck-Sickinger, Annette G. )
• A05 - Development of an optical platform to characterize (surface-)binding reactions between glycosaminoglycans and mediators (Project Head Schwille, Petra )
• A06 - Investigation of the interaction of mediators with matrix components and analysis of the extracellular matrix by NMR methods (Project Head Huster, Ph.D., Daniel )
• A07 - Modeling and simulation of glycosaminoglycan/protein interactions (Project Head Pisabarro, María Teresa )
• A08 - Chemoenzymatic synthesis of defined sulfated oligohyaluronans for binding studies and the construction of artificial extracellular matrices (Project Heads Rademann, Jörg ;  Schiller, Jürgen )
• A09 - Automated synthesis of glycosaminoglycans (Project Head Seeberger, Peter H. )
• A10 - Glycosaminoglycan-poly (ethylene glycol) hydrogels for improving dermal wound healing (Project Heads Freudenberg, Uwe ;  Werner, Carsten )
• B01 - Influence of artificial and native extracellular matrices on adhesion and differentiation of mesenchymal stem cells and osteoblasts (Project Head Hempel, Ute )
• B02 - Effects of sulfated glycosaminoglycans on bone regeneration through interactions with Wnt inhibitors (Project Heads Hofbauer, Lorenz C. ;  Hofbauer, Christine )
• B03 - Immune responses to native and artificial extracellular matrices (Project Heads Franz, Sandra ;  Simon, Jan-Christoph )
• B04 - Impact of artificial extracellular matrix on fibroblast functions (Project Heads Anderegg, Ulf ;  Saalbach, Anja )
• B05 - In vivo- and in vitro-investigation of the effects of artificial matrices on implant surfaces in long bones (Project Heads Pietzsch, Jens ;  Rammelt, Stefan ;  Zwipp, Hans )
• B06 - Analysis of newly designed implant surface coatings: a maxillofacial animal model (Project Heads Eckelt, Uwe ;  Mai, Ronald )
• B08 - Three-dimensional analysis of in vivo reactions to artificial extracellular matrices (Project Heads Scharnweber, Dieter ;  Scheler, Ulrich )
• B09 - Modulation of tissue regeneration by the glycosaminoglycan-binding anti-inflammatory cytokine interleukin-10 (Project Head Roers, Axel )
• B10 - In situ characterization of mediator controlled immune cell interaction in GAG-modified aECM (Project Head Pompe, Tilo )
• B11 - The role of heparan sulfate proteoglycans during zebrafish bone regeneration (Project Heads Brand, Michael ;  Knopf, Franziska )
• T01 - Sulfated glycoaminoglycans as coating for endoprostheses to improve osseointegration (Project Heads Hofbauer, Lorenz C. ;  Rammelt, Stefan ;  Schnabelrauch, Matthias )
• Z01 - Central administration of collaborative research centre (Project Heads Scharnweber, Dieter ;  Simon, Jan-Christoph )
• Z02 - Integrated Research Training Group "Matrix Engineering" (Project Heads Beck-Sickinger, Annette G. ;  Scharnweber, Dieter ;  Werner, Carsten )
• Z03 - Synthesis and allocation of oligomeric and polymeric glycosaminoglycans and artificial extracellular matrices (Project Heads Giannis, Athanassios ;  Scharnweber, Dieter ;  Schiller, Jürgen ;  Schnabelrauch, Matthias )
• Z04 - Proteomics platform for analysis of matrix-induced effects in in vivo- and in vitro-model systems (Project Heads Averbeck, Marco ;  von Bergen, Martin ;  Kalkhof, Stefan ;  van Pée, Karl-Heinz )

• Applicant Institution: Universität Leipzig
• Co-Applicant Institution: Technische Universität Dresden
• Participating University: Freie Universität Berlin
• Participating Institution: Helmholtz-Zentrum für Umweltforschung - UFZ; Themenbereich Chemikalien in der Umwelt; Department Molekulare Systembiologie; INNOVENT Technologieentwicklung Jena e.V.; Forschungsbereich Biomaterialien; Leibniz-Institut für Polymerforschung Dresden e.V.; Institut Biofunktionelle Polymermaterialien; im Max Bergmann Center of Biomaterials Dresden; Helmholtz-Zentrum Dresden-Rossendorf (HZDR); Institut für Radiopharmazeutische Krebsforschung
• Spokesperson: Professor Dr. Jan-Christoph Simon