Identification and functional characterization of novel nanofiber-growth factor hybrid molecules for regeneration in a mouse traumatic brain injury model

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Mechanical injury of organs and tissues induces cavity formation resulting in cellular demise and disruption of cell-to-cell contacts. Research in tissue regeneration aims at enhancing recovery of such injured cells and reconstitution of cellular function. One approach in tissue engineering and regenerative medicine is to investigate and exploit the potential of new bioactive molecules that can be employed to fill such cavities in order to facilitate cellular and molecular regeneration processes.In this proposal we want to explore a new type of bioactive material in tissue regeneration. So-called self-assembling peptides (SAPs) are short sequences of amino acids (typically 6-12) that spontaneously polymerize into supramolecular nanofibers. Such nanofibers build higher ordered structures, for instance two- and three-dimensional networks resembling the extracellular matrix surrounding tissues in living organisms. The rational of this proposal is to use such nanofiber networks as "tissue glue" filling lesion gaps of injured organs to promote adhesion and growth of damaged cells. Based on our previous published work demonstrating already the positive activities of such SAP derived nanofibers in cell culture and in animal models we want to further improve the regeneration stimulating potential of this biomaterial. For this, SAP derived nanofibers will be further functionalized by chemical conjugation of additional biologically active molecules such as growth factors. The resulting assemblies will be analyzed for physico-chemical parameters that were previously correlated with high regenerative potential. Subsequently, such hybrid nanofibers will be tested in several regeneration experiments using the injured brain as model system. First of all, we analyze whether such functionalized nanofibers serve as growth substrate to enhance adhesion and axon growth of neurons in cell culture. Successful candidates will be carried forward to a mouse model of traumatic brain injury (TBI), one of the leading causes of mortality and disability in young adults. Here, nanofibers will be injected into the cavity of the injured brain and we will subsequently monitor regeneration animals by several parameters including recovery of motor performance. Expecting a positive activity of this new biomaterial in regeneration after TBI in an animal model we believe that regenerative approaches of other injured organs (e.g. bone, skin and muscle) might likewise benefit from this proposal.