CoLOsAM - Collagen Laminates with Osteoinductive and AntiMicrobial properties

• Applicants: Professorin Dr.-Ing. Daniela Nickel; Professorin Dr. Ulrike Ritz; Professorin Dr. Katja Schmitz
• Subject Area: Biomaterials ; Synthesis and Properties of Functional Materials ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 400569699

Fracture healing of defects of critical sizes remains a challenge for surgeons all over the world. Until now, there is still no agreement concerning the ideal strategy for therapy. Many studies demonstrated that the critical point for bone tissue engineering is not the induction of bone growth but vascularization of the implant. Moreover, bacterial infection resulting from open wounds interferes with the healing of bone defects. There is substantial need for a flexible management of open fractures to avoid infection, and to support tissue regeneration depending on the severity of the open fractures.In the proposed project we want to develop and characterize a multilayer biomaterial – laminate like - based on collagen films with antibacterial, osteoinductive and angioinductive properties. Antibacterial, osteoinductive and / or angiogenesis-inducing agents will be incorporated into layers of biodegradable materials (collagen). Adsorption of bioactive antimicrobial compounds within the outer hydrogel layer will ensure an initial burst of antibiotics shortly after administration of the new biomaterial to eradicate contaminating bacteria. A burst of osteogenic as well as angiogenic agents will trigger osteoblast and stem cell migration and differentiation to initiate the healing process. The same compounds will be confined to the inner hydrogel layers by crosslinking to ensure sustained release as the matrix is gradually degraded by infiltrating cells. The macroscopic multilayer structure and microscopic reduction of the pore sizes of the biomaterial by crosslinking will permit customized assembly of biodegradable sheets with different compounds and loading densities according to the individual needs of the healing process. Compound release and biomaterial degradation will be characterized in vitro with different human cells (cell lines and primary cells) and correlated to loading methods and crosslinking. The influence of crosslinking and exposure on the different cell types on the mechanical properties of individual sheets and multi-sheet laminates will be elucidated to identify optimal parameters for crosslinking. By these means multi-sheet laminates with defined mechanical properties and release profiles for antimicrobials and osteoinductive compounds for application after trauma can be fabricated. With our flexible collagen laminate membrane system, surgeons could respond to the individual patients´ demands depending on severity of bacterial contamination, tissue and vascularization damage and optimize the combination and loading of the collagen laminate constituents. The three participants combine the expertise for developing and characterizing the laminate biomaterial: Daniela Nickel for material characterization and mechanical behavior, Katja Schmitz for loading and combining the laminate constituents and quantification of compound release and Ulrike Ritz for analyzing the biocompatibility and effects of compound release on bacteria and cells.

• DFG Programme: Research Grants