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

器官和组织的机械损伤诱导空腔形成，导致细胞死亡和细胞与细胞接触的破坏。组织再生的研究旨在促进这些受损细胞的恢复和细胞功能的重建。组织工程和再生医学的一个重要方向是研究和开发新的生物活性分子，使其能够填充这些空洞，从而促进细胞和分子的再生过程，本研究旨在探索一种新型的生物活性材料用于组织再生。所谓的自组装肽（SAP）是短序列的氨基酸（通常为6-12个），其自发地折叠成超分子纳米纤维。这样的纳米纤维构建更高的有序结构，例如类似于活生物体中组织周围的细胞外基质的二维和三维网络。其合理性在于利用这种网状结构作为“组织胶”填充受损器官的损伤间隙，促进受损细胞的粘附和生长。基于我们先前发表的工作，已经证明了这种SAP衍生的纳米纤维在细胞培养物和动物模型中的积极活性，我们希望进一步提高这种生物材料的再生刺激潜力。为此，SAP衍生的纳米纤维将通过另外的生物活性分子如生长因子的化学缀合而进一步官能化。将分析所得组件的物理化学参数，这些参数先前与高再生潜力相关。随后，这种混合纳米纤维将在几个再生实验中使用受损的大脑作为模型系统进行测试。首先，我们分析了这种功能化的纳米纤维是否作为生长基质，以增强细胞培养中神经元的粘附和轴突生长。成功的候选人将被带到创伤性脑损伤（TBI）的小鼠模型中，这是年轻人死亡和残疾的主要原因之一。在这里，纳米纤维将被注射到受伤大脑的空腔中，我们随后将通过几个参数监测再生动物，包括运动性能的恢复。预期这种新的生物材料在动物模型中TBI后的再生中具有积极的活性，我们认为其他受损器官（例如骨骼、皮肤和肌肉）的再生方法也可能受益于该提议。

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.