Yuanfang Huo , Yannan Cheng , Xianzhen Dong , Qiang Cheng , Xinyue Liang , Ping Duan , Yongle Yu , Lesan Yan , Tong Qiu , Zhenyu Pan , Honglian Dai
{"title":"Pleiotropic effects of nitric oxide sustained-release system for peripheral nerve repair","authors":"Yuanfang Huo , Yannan Cheng , Xianzhen Dong , Qiang Cheng , Xinyue Liang , Ping Duan , Yongle Yu , Lesan Yan , Tong Qiu , Zhenyu Pan , Honglian Dai","doi":"10.1016/j.actbio.2024.05.012","DOIUrl":null,"url":null,"abstract":"<div><p>The regenerative microenvironment after peripheral nerve injury is imbalanced and difficult to rebalance, which is mainly affected by inflammation, oxidative stress, and inadequate blood supply. The difficulty in remodeling the nerve regeneration microenvironment is the main reason for slow nerve regeneration. Traditional drug treatments have certain limitations, such as difficulty in penetrating the blood-nerve barrier and lack of pleiotropic effects. Therefore, there is an urgent need to build multifunctional nerve grafts that can effectively regulate the regenerative microenvironment and promote nerve regeneration. Nitric oxide (NO), a highly effective gas transmitter with diatomic radicals, is an important regulator of axonal growth and migration, synaptic plasticity, proliferation of neural precursor cells, and neuronal survival. Moreover, NO provides potential anti-inflammation, anti-oxidation, and blood vessel promotion applications. However, excess NO may cause cell death and neuroinflammatory cell damage. The prerequisite for NO treatment of peripheral nerve injury is that it is gradually released over time. In this study, we constructed an injectable NO slow-release system with two main components, including macromolecular NO donor nanoparticles (mPEG-P(MSNO-EG) nanoparticles, NO-NPs) and a carrier for the nanoparticles, mPEG-PA-PP injectable temperature-sensitive hydrogel. Due to the multiple physiological regulation of NO and better physiological barrier penetration, the conduit effectively regulates the inflammatory response and oxidative stress of damaged peripheral nerves, promotes nerve vascularization, and nerve regeneration and docking, accelerating the nerve regeneration process.</p></div><div><h3>Statement of significance</h3><p>The slow regeneration speed of peripheral nerves is mainly due to the destruction of the regeneration microenvironment. Neural conduits with drug delivery capabilities have the potential to improve the microenvironment of nerve regeneration. However, traditional drugs are hindered by the blood nerve barrier and cannot effectively target the injured area. NO, an endogenous gas signaling molecule, can freely cross the blood nerve barrier and act on target cells. However, excessive NO can lead to cell apoptosis. In this study, a NO sustained-release system was constructed to regulate the microenvironment of nerve regeneration through various pathways and promote nerve regeneration.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4000,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Biomaterialia","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1742706124002472","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
The regenerative microenvironment after peripheral nerve injury is imbalanced and difficult to rebalance, which is mainly affected by inflammation, oxidative stress, and inadequate blood supply. The difficulty in remodeling the nerve regeneration microenvironment is the main reason for slow nerve regeneration. Traditional drug treatments have certain limitations, such as difficulty in penetrating the blood-nerve barrier and lack of pleiotropic effects. Therefore, there is an urgent need to build multifunctional nerve grafts that can effectively regulate the regenerative microenvironment and promote nerve regeneration. Nitric oxide (NO), a highly effective gas transmitter with diatomic radicals, is an important regulator of axonal growth and migration, synaptic plasticity, proliferation of neural precursor cells, and neuronal survival. Moreover, NO provides potential anti-inflammation, anti-oxidation, and blood vessel promotion applications. However, excess NO may cause cell death and neuroinflammatory cell damage. The prerequisite for NO treatment of peripheral nerve injury is that it is gradually released over time. In this study, we constructed an injectable NO slow-release system with two main components, including macromolecular NO donor nanoparticles (mPEG-P(MSNO-EG) nanoparticles, NO-NPs) and a carrier for the nanoparticles, mPEG-PA-PP injectable temperature-sensitive hydrogel. Due to the multiple physiological regulation of NO and better physiological barrier penetration, the conduit effectively regulates the inflammatory response and oxidative stress of damaged peripheral nerves, promotes nerve vascularization, and nerve regeneration and docking, accelerating the nerve regeneration process.
Statement of significance
The slow regeneration speed of peripheral nerves is mainly due to the destruction of the regeneration microenvironment. Neural conduits with drug delivery capabilities have the potential to improve the microenvironment of nerve regeneration. However, traditional drugs are hindered by the blood nerve barrier and cannot effectively target the injured area. NO, an endogenous gas signaling molecule, can freely cross the blood nerve barrier and act on target cells. However, excessive NO can lead to cell apoptosis. In this study, a NO sustained-release system was constructed to regulate the microenvironment of nerve regeneration through various pathways and promote nerve regeneration.
周围神经损伤后的再生微环境失衡且难以恢复,主要受炎症、氧化应激和供血不足的影响。神经再生微环境难以重塑是神经再生缓慢的主要原因。传统的药物治疗存在一定的局限性,如难以渗透血神经屏障、缺乏多效性等。因此,建立能有效调节再生微环境、促进神经再生的多功能神经移植物迫在眉睫。一氧化氮(NO)是一种含有二原子自由基的高效气体递质,是轴突生长和迁移、突触可塑性、神经前体细胞增殖和神经元存活的重要调节因子。此外,NO 还具有潜在的抗炎、抗氧化和促进血管的作用。然而,过量的 NO 可能会导致细胞死亡和神经炎症细胞损伤。NO 治疗周围神经损伤的先决条件是它能随着时间的推移逐渐释放。本研究中,我们构建了一种可注射的 NO 缓释系统,该系统主要由两部分组成,包括大分子 NO 供体纳米颗粒(mPEG-P(MSNO-EG) 纳米颗粒,NO-NPs)和纳米颗粒的载体 mPEG-PA-PP 可注射温敏水凝胶。由于NO的多重生理调节作用和较好的生理屏障渗透作用,该导管能有效调节受损周围神经的炎症反应和氧化应激,促进神经血管化和神经再生对接,加速神经再生进程。意义声明:周围神经再生速度慢的主要原因是再生微环境的破坏。具有药物输送功能的神经导管有望改善神经再生的微环境。然而,传统药物受到血神经屏障的阻碍,无法有效靶向损伤区域。NO是一种内源性气体信号分子,可以自由穿越血神经屏障,作用于靶细胞。然而,过量的 NO 会导致细胞凋亡。本研究构建了一种 NO 持续释放系统,通过多种途径调节神经再生的微环境,促进神经再生。
期刊介绍:
Acta Biomaterialia is a monthly peer-reviewed scientific journal published by Elsevier. The journal was established in January 2005. The editor-in-chief is W.R. Wagner (University of Pittsburgh). The journal covers research in biomaterials science, including the interrelationship of biomaterial structure and function from macroscale to nanoscale. Topical coverage includes biomedical and biocompatible materials.