Brain injury can lead to the loss of neuronal functions and connections, along with the damage of the extracellular matrix (ECM). Thus, it ultimately results in devastating long-term damage, and recovery from this damage is a challenging task. To address this issue, we have designed a sulfo-group-functionalized injectable biocompatible peptide hydrogel, which not only mimics the ECM and supports the damaged neurons but also releases a neurotrophic factor around the injured sites of the brain in the presence of the matrix metalloproteinase 9 (MMP9) enzyme. It has also been observed that the driving force of hydrogel formation is a β-sheet secondary structure and π–π stacking interactions between Phe-Phe moieties. The hydrogel is able not only to promote neurite outgrowth of PC12-derived neurons and primary neurons cultured in its presence but also to nullify the toxic effects of anti-nerve growth factor (Anti-NGF)-induced neurons. It also promotes the expression of vital neuronal markers in rat cortical primary neurons, displays substantial potential in neuroregeneration, and also promotes fast recovery of the sham injured mice brain. Increased expression of reactive astrocytes in the hippocampal dentate gyrus region of the sham injured brain clearly suggests its tremendous ability in the neural repair of the damaged brain. Thus, we can convincingly state that our hydrogel is capable of repairing brain injury by mimicking an ECM-like environment and providing neuroprotection to the damaged neurons.

中文翻译：

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细胞外基质（ECM）模拟神经保护性注射的磺基功能化肽水凝胶修复脑损伤。

脑损伤可导致神经元功能和连接的丧失，以及细胞外基质（ECM）的损害。因此，它最终导致毁灭性的长期破坏，而从这种破坏中恢复是一项艰巨的任务。为了解决这个问题，我们设计了一种具有磺基功能的可注射生物相容性肽水凝胶，该凝胶不仅模仿ECM并支持受损的神经元，而且在存在基质金属蛋白酶的情况下，在大脑受伤部位周围释放神经营养因子。 9（MMP9）酶。还已经观察到，水凝胶形成的驱动力是β-折叠二级结构和Phe-Phe部分之间的π-π堆积相互作用。水凝胶不仅能够促进在其存在下培养的PC12衍生神经元和原代神经元的神经突向外生长，而且还能抵消抗神经生长因子（Anti-NGF）诱导的神经元的毒性作用。它还促进大鼠皮质原代神经元中重要神经元标志物的表达，在神经再生中显示出巨大潜力，并且还促进假伤小鼠大脑的快速恢复。假伤脑海马齿状回区域中反应性星形胶质细胞表达的增加清楚地表明了其在受损脑神经修复中的巨大能力。因此，我们可以令人信服地指出，我们的水凝胶能够通过模仿类似ECM的环境并为受损的神经元提供神经保护来修复脑损伤。