mRNA-containing fibrous conduits for repair of long-gap peripheral nerve injury
含有 mRNA 的纤维导管用于修复长间隙周围神经损伤
基本信息
- 批准号:10588480
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-01-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AllograftingAutologousAutologous TransplantationBiocompatible MaterialsCellsChemicalsChicagoClinicalClinical MedicineCollaborationsComplications of Diabetes MellitusDNADefectDevelopmentDiabetes MellitusDiabetic NeuropathiesDiseaseDistalDrug Delivery SystemsExtracellular MatrixFiberFosteringGrowth FactorHarvestHealthImmunosuppressionInfiltrationInjuryInterdisciplinary StudyInvestigationLesionMacrophageMessenger RNAMilitary PersonnelModelingMorbidity - disease rateNatural regenerationNerveNerve RegenerationNerve TissueNeuritesNeurotrophin 3OutcomePatientsPeripheralPeripheral NervesPeripheral Nervous System DiseasesPeripheral nerve injuryPharmaceutical PreparationsPolymersPre-Clinical ModelPreparationProceduresProcessProductionProteinsPublicationsRattusRecoveryRecovery of FunctionRegenerative responseResearchResearch InstituteSchwann CellsScienceShapesSiteSpinal GangliaSurfaceSurgical suturesTestingTissue DonorsTissue EngineeringTissuesUnited StatesVeteransWorkaxon growthaxon regenerationbiodegradable polymerbioscaffoldcell growthcell motilitycomorbiditydesigndisabilityeffectiveness evaluationexperimental studyimplantationimprovedin vivo ModelinjuredinnovationmRNA deliverymilitary health systemmilitary veterannerve autograftnerve gapnerve injurynerve repairneuralnovelnovel strategiesperformance siteperipheral nerve regenerationperipheral nerve repairpoly-L-lactic acidpre-clinicalprotein expressionprototyperegenerativerepairedresponsescaffoldsciatic nervesmall moleculestem cellssural nervetooltumor
项目摘要
Project Summary/Abstract
Peripheral nerve injury remains a significant problem in the United States and among the Veteran population.
Even after decades of research, there are few clinically available approaches to treat long-gap peripheral nerve
injury. Often, long-gap peripheral nerve repair is facilitated through harvest and placement of sural nerve
autografts into the injury site. Sural nerve isolation induces donor site morbidity, and some patients are unable
to donate neural tissue due to other co-morbidities (such as diabetes). As alternatives to the autografts, nerve
allografts and biomaterial scaffolds have emerged as possible approaches to supplant the autograft. However,
allografts require extensive decellularization processes, and it is challenging to find size-matched allografts for
patients. Biomaterial conduits can be shaped into appropriate sizes. Many biomaterial conduits lack sufficient
extracellular matrix to promote extensive regeneration of axons. In total, autograft, allograft, and biomaterial
strategies routinely fail to completely rescue lost function. Thus, new strategies are needed to advance the
field. Biomaterial conduits that consist of aligned, electrospun fibers robustly promote axonal regeneration in
preclinical models of peripheral nerve injury. Fibrous materials are produced using synthetic, degradable
polymers that contain no extracellular matrix. Schwann cells migrating into the injury site are responsible for
producing sufficient ECM to foster robust regeneration. Unfortunately, Schwann cells immediately after
peripheral nerve injury reduce their production of key growth factors, such as neurotrophin-3 (NT-3). Therefore,
Schwann cells are unable to produce sufficient factors to create ECM and growth factors to robustly induce
regeneration. Inclusion of exogenous stem cells and Schwann cells that release regenerative factors or use of
biomaterials that release growth factors improve regeneration in preclinical models. However, cellular explants
from donor tissue require immunosuppression, and it is difficult to release proteins from degradable polymers
(which typically require harsh chemicals for polymer synthesis). Harsh chemicals used to fabricate biomaterial
scaffolds denature growth factors, requiring investigation of alternative approaches. In this SPiRE application,
we propose to develop mRNA-releasing fibrous scaffolds and assess the ability of the mRNA-releasing
scaffolds to promote peripheral regeneration in a pre-clinical injury model. In total, the development of new
biomaterial approaches to treat peripheral nerve injury may lead to new tools capable of promoting robust
peripheral nerve regeneration for the Veteran population.
项目摘要/摘要
在美国和退伍军人人口中,周围神经损伤仍然是一个重大问题。
即使经过数十年的研究,几乎没有临床上可用的方法来治疗长距离周围神经
受伤。通常,通过收获和舒适神经的放置来促进长距离周围神经修复
自体移植到伤害部位。 Sural神经隔离会引起供体部位的发病率,有些患者无法
由于其他合并症(例如糖尿病),捐赠神经组织。作为自体移植的替代品,神经
同种异体移植物和生物材料支架已成为取代自体移植的方法。然而,
同种异移植需要广泛的脱细胞过程,找到尺寸匹配的同种异体移植物是一项挑战
患者。生物材料的导管可以分为适当的尺寸。许多生物材料的导管缺乏足够的
细胞外基质以促进轴突的广泛再生。总共自体移植,同种异体移植和生物材料
策略通常无法完全挽救丢失的功能。因此,需要新的策略来推进
场地。由对齐的,电纺纤维组成的生物材料导管可靠地促进轴突再生
周围神经损伤的临床前模型。纤维材料是使用合成的,可降解的
没有包含细胞外基质的聚合物。 Schwann细胞迁移到伤害部位的原因是
产生足够的ECM来促进鲁棒的再生。不幸的是,Schwann细胞紧随其后
周围神经损伤减少了关键生长因子的产生,例如Neurotrophin-3(NT-3)。所以,
Schwann细胞无法产生足够的因素来创建ECM和生长因子以鲁棒性诱导
再生。包括释放再生因子或使用的外源干细胞和雪旺氏细胞
释放生长因子的生物材料改善了临床前模型的再生。但是,蜂窝外植体
从供体组织需要免疫抑制,并且很难从可降解的聚合物中释放蛋白质
(通常需要用于聚合物合成的刺激性化学物质)。用于制造生物材料的苛刻化学物质
脚手架变性生长因子,需要研究替代方法。在此尖峰应用中,
我们建议开发释放mRNA的纤维支架并评估mRNA释放的能力
在临床前损伤模型中促进外围再生的脚手架。总体而言,新的发展
治疗周围神经损伤的生物材料方法可能会导致能够促进强大的新工具
退伍军人人口的周围神经再生。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Ryan J. Gilbert其他文献
Construction of an Elastin-like Polypeptide Gene in a High Copy Number Plasmid Using a Modified Method of Recursive Directional Ligation
使用改进的递归定向连接方法在高拷贝数质粒中构建弹性蛋白样多肽基因
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Derek W. Nelson;Alexander Connor;Yu Shen;Ryan J. Gilbert - 通讯作者:
Ryan J. Gilbert
Ryan J. Gilbert的其他文献
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{{ truncateString('Ryan J. Gilbert', 18)}}的其他基金
Development of Poly (pro-curcumin) Polymer Coatings to Improve Cortical Electrode Biocompatibility
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- 批准号:
10352198 - 财政年份:2021
- 资助金额:
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开发聚(姜黄素原)聚合物涂层以改善皮质电极生物相容性
- 批准号:
10543083 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Development of Poly (pro-curcumin) Polymer Coatings to Improve Cortical Electrode Biocompatibility
开发聚(姜黄素原)聚合物涂层以改善皮质电极生物相容性
- 批准号:
10187720 - 财政年份:2021
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Enhanced Neuroprotection Following Acute SCI Using Fibrous Materials
使用纤维材料增强急性 SCI 后的神经保护
- 批准号:
9265525 - 财政年份:2015
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Development of Biomaterials that Release Therapeutic Agents to Modulate Inflammat
开发释放治疗剂来调节炎症的生物材料
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8192640 - 财政年份:2009
- 资助金额:
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