Huang Xuyang, Ye Yongqing, Zhang Jianyong, Zhang Xuefeng, Ma Hongwei, Zhang Yongkang, Fu Xianhua, Tang JiaJia, Jiang Ning, Han Yuhan, Liu Hongmei, Chen Honglin
Department of Neurosurgery, The Suqian Clinical College of Xuzhou Medical University, Jiangsu University, Suqian 223800, People's Republic of China.
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou 221002, People's Republic of China.
ACS Appl Mater Interfaces. 2022 Jul 14. doi: 10.1021/acsami.2c04930.
Traumatic brain injury (TBI) is accompanied by the overload of reactive oxygen species (ROS), which can result in secondary brain injury. Although procyanidins (PCs) have a powerful free radical scavenging capability and have been widely studied in the treatment of TBI, conventional systemic drug therapy cannot make the drug reach the targeted area in the early stage of TBI and will cause systemic side effects because of the presence of the blood-brain barrier (BBB). To address this tissue, we designed and fabricated a ROS-scavenging functional hydrogel loaded PC (GelMA-PPS/PC) to deliver the drug by responding to the traumatic microenvironment. injection of the GelMA-PPS/PC hydrogel effectively avoided the BBB and was directly applied to the surface of brain tissue to target the traumatic area. Hydrophobic poly(propylene sulfide) (PPS), an ROS quencher and HO-responsive substance, was covalently bound to GelMA and exposed in response to the trauma microenvironment. At the same time, the HO response of PPS further caused the structure of the hydrogel to degrade and release the encapsulated PC. Then PC could regulate the oxidative stress response in the cells and synergistically deplete ROS to play a neurotrophic protective role. This work suggests a novel method for the treatment of secondary brain injury by inhibiting the oxidative stress response after TBI.
创伤性脑损伤(TBI)伴随着活性氧(ROS)过载,这会导致继发性脑损伤。尽管原花青素(PCs)具有强大的自由基清除能力,并且在TBI治疗中已得到广泛研究,但传统的全身药物治疗无法使药物在TBI早期到达靶区域,并且由于血脑屏障(BBB)的存在会引起全身副作用。为了解决这个问题,我们设计并制备了一种负载PC的ROS清除功能水凝胶(GelMA-PPS/PC),通过对创伤微环境的响应来递送药物。注射GelMA-PPS/PC水凝胶有效地避开了血脑屏障,并直接应用于脑组织表面以靶向创伤区域。疏水性聚(硫化丙烯)(PPS)是一种ROS淬灭剂和HO响应物质,与GelMA共价结合,并在创伤微环境的响应下暴露。同时,PPS的HO响应进一步导致水凝胶结构降解并释放包封的PC。然后PC可以调节细胞中的氧化应激反应并协同消耗ROS以发挥神经营养保护作用。这项工作提出了一种通过抑制TBI后氧化应激反应来治疗继发性脑损伤的新方法。