Huang Abel Po-Hao, Lai Dar-Ming, Hsu Yi-Hua, Tsai Hsin-Han, Su Chia-Yi, Hsu Shan-Hui
Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, ROC; Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, ROC.
Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, ROC.
Mater Sci Eng C Mater Biol Appl. 2021 Feb;121:111799. doi: 10.1016/j.msec.2020.111799. Epub 2020 Dec 16.
Hemostasis plays a fundamental and critical role in all surgical procedures. However, the currently used topical hemostatic agents may at times undesirably induce inflammation, infection, and foreign body reaction and hamper the healing process. This may be serious in the central nervous system (CNS), especially for some neurosurgical diseases which have ongoing inflammation causing secondary brain injury. This study was aimed to develop a hemostatic agent with anti-inflammatory property by incorporating carboxyl-functionalized biodegradable polyurethane nanoparticles (PU NPs) and to evaluate its functionality using a rat neurosurgical model. PU NPs are specially-designed anti-inflammatory nanoparticles and absorbed by a commercially available hemostatic gelatin powder (Spongostan™). Then, the gelatin was implanted to the injured rat cortex and released anti-inflammatory PU NPs. The time to hemostasis, the cerebral edema formation, and the brain's immune responses were examined. The outcomes showed that PU NP-contained gelatin attenuated the brain edema, suppressed the gene expression levels of pro-inflammatory M1 biomarkers (e.g., IL-1β level to be about 25%), elevated the gene expression levels of anti-inflammatory M2 biomarkers (e.g., IL-10 level to be about 220%), and reduced the activation of inflammatory cells in the implanted site, compared with the conventional gelatin. Moreover, PU NP-contained gelatin increased the gene expression level of neurotrophic factor BDNF by nearly 3-folds. We concluded that the PU NP-contained hemostatic agents are anti-inflammatory with neuroprotective potential in vivo. This new hemostatic agent will be useful for surgery involving vulnerable tissue or organ (e.g., CNS) and also for diseases such as stroke, traumatic brain injury, and neurodegenerative diseases.
止血在所有外科手术中都起着至关重要的作用。然而，目前使用的局部止血剂有时可能会意外地引发炎症、感染和异物反应，并阻碍愈合过程。这在中枢神经系统（CNS）中可能很严重，尤其是对于一些存在持续炎症导致继发性脑损伤的神经外科疾病。本研究旨在通过将羧基功能化的可生物降解聚氨酯纳米颗粒（PU NPs）纳入其中来开发一种具有抗炎特性的止血剂，并使用大鼠神经外科模型评估其功能。PU NPs是经过特殊设计的抗炎纳米颗粒，并被市售的止血明胶粉（Spongostan™）吸收。然后，将明胶植入受伤的大鼠皮质并释放抗炎的PU NPs。检测止血时间、脑水肿形成情况以及大脑的免疫反应。结果表明，与传统明胶相比，含PU NP的明胶减轻了脑水肿，抑制了促炎M1生物标志物的基因表达水平（例如，IL-1β水平降至约25%），提高了抗炎M2生物标志物的基因表达水平（例如，IL-10水平升至约220%），并减少了植入部位炎症细胞的活化。此外，含PU NP的明胶使神经营养因子BDNF的基因表达水平提高了近3倍。我们得出结论，含PU NP的止血剂在体内具有抗炎和神经保护潜力。这种新型止血剂将有助于涉及脆弱组织或器官（如中枢神经系统）的手术，也可用于治疗中风、创伤性脑损伤和神经退行性疾病等疾病。
