A Novel High-Intensity Iontophoresis-Based Antibiotic Delivery Device for Efficacious Eradication of Chronic Wound Biofilms
一种新型高强度离子电渗疗法抗生素输送装置,可有效根除慢性伤口生物膜
基本信息
- 批准号:10433163
- 负责人:
- 金额:$ 16.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-03 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAmputationAntibiotic ResistanceAntibioticsBacteriaBiologicalBiological ModelsCell Culture TechniquesCellsCharacteristicsChronicComputer AssistedDevice DesignsDevicesDiffusionDrug Delivery SystemsDrug resistanceElementsExtracellular MatrixFormulationGoalsGrowthHealthHealth Care CostsHourHumanHydrogelsIn VitroInfectionInflammatoryInflammatory ResponseIonsIontophoresisMicrobial BiofilmsMissionModelingNational Institute of Arthritis and Musculoskeletal and Skin DiseasesOutcomePatientsPersonsPhasePolymersProcessPublic HealthQuality of lifeRattusResearchSafetySkinSkin TissueSurgical FlapsTechnologyTemperatureTimeTissuesTopical applicationTreatment EfficacyVancomycinVancomycin ResistanceWound Infectionantibiotic designbasechronic woundcombatdesignextracellularhealingimprovedin vivometabolic ratemethicillin resistant Staphylococcus aureusmortalitynanoparticlenon-healing woundsnovelpreventresistance genesimulationskin regenerationsmall moleculetherapeutically effectivewoundwound biofilmwound healing
项目摘要
PROJECT SUMMARY. In this study, we will develop a novel ion current-based iontophoresis device that can
safely apply high intensity currents to deliver a therapeutically effective concentration of antibiotics into biofilms
within a short period of time to achieve efficacious eradication of chronic wound biofilm infections. Chronic
wounds are currently affecting more than 6 million people in the US. More than 78% of chronic wounds have
biofilms, which arrest the wounds in a prolonged inflammatory phase and prevent wound healing. Biofilms are
difficult to treat, because biofilm bacteria are more resistant to antibiotics and a protective matrix of extracellular
polymeric substances reduce the diffusion rate of antibiotics into biofilms. As a result, current antibiotic delivery
technologies are not capable of delivering sufficient antibiotic concentrations to effectively eradicate chronic
wound biofilm infections.
Iontophoresis is a non-invasive, electrical current-based drug delivery technology. Conventional iontophoresis
devices have low antibiotic delivery efficiency due to the low current intensities they use. Although higher current
intensities increase antibiotic delivery efficiency, they can cause significant tissue burn due to the temperature
increase and the pH changes at the device/tissue interface. In this proposal, based on an ion current-conducting
hydrogel ionic circuit (HIC) invented in our lab, we aim to develop a novel iontophoresis device that can safely
apply current intensities that are significantly higher than what current iontophoresis devices use. Higher current
intensities will allow us to deliver significantly higher amount of antibiotics to efficaciously eliminate biofilm
bacteria and restore the normal wound healing process. In Specific Aim 1, we will first design and optimize an
HIC-based, skin-mountable iontophoretic antibiotic delivery device through computer-aided finite-element
simulation. We will then determine the antibiotic delivery efficiency and biofilm eradication efficacy of our device
using an excised human skin-based wound infection model. The safety of high-intensity ion current application
will also be evaluated using in vitro cell cultures and healthy rats. In Specific Aim 2, we will determine the in vivo
biofilm eradication efficacy and wound healing enhancement efficacy of our device using a rat bipedicled skin
flap-based ischemic wound infection model. Our outcome will establish an optimal device design and a critical
proof-of-concept for the in vivo safety, biofilm eradication efficacy, and chronic wound healing enhancement
efficacy of our high-intensity iontophoretic antibiotic delivery device. The enhanced healing of chronic wounds
enabled by our device will greatly improve the quality of life for patients and reduce the overall healthcare cost.
项目摘要。在本研究中,我们将开发一种新型的基于离子电流的离子电渗装置,
安全地施加高强度电流以将治疗有效浓度的抗生素递送到生物膜中
以实现慢性伤口生物膜感染的有效根除。慢性
目前,美国有超过600万人受到创伤的影响。超过78%的慢性伤口
生物膜,其在延长的炎症阶段阻止伤口并防止伤口愈合。生物膜是
很难治疗,因为生物膜细菌对抗生素和细胞外基质的保护性基质更具抗性。
聚合物物质降低抗生素向生物膜中的扩散速率。因此,目前的抗生素输送
技术不能提供足够的抗生素浓度来有效地根除慢性
伤口生物膜感染。
离子电渗疗法是一种非侵入性的、基于电流的药物递送技术。常规离子导入
装置由于其使用的电流强度低而具有低的抗生素输送效率。虽然目前
强度增加抗生素递送效率,它们可由于温度而引起显著的组织烧伤
增加,器械/组织界面的pH值发生变化。在该提议中,基于离子电流传导
本实验室开发的水凝胶离子电路(HIC),旨在开发一种新型的离子电渗装置,
施加明显高于当前离子电渗疗法装置使用的电流强度。较高电流
强度将允许我们递送显著更高量的抗生素以有效地消除生物膜
细菌和恢复正常的伤口愈合过程。在具体目标1中,我们将首先设计和优化
通过计算机辅助有限元的基于皮肤的可安装在皮肤上的离子电渗抗生素递送装置
仿真然后,我们将确定我们的装置的抗生素递送效率和生物膜根除功效
使用基于离体人类皮肤的伤口感染模型。高强度离子流应用的安全性
还将使用体外细胞培养物和健康大鼠进行评价。在具体目标2中,我们将确定体内
我们的装置使用大鼠双蒂皮肤的生物膜根除功效和伤口愈合增强功效
皮瓣缺血性伤口感染模型。我们的结果将建立一个最佳的设备设计和一个关键的
体内安全性、生物膜根除有效性和慢性伤口愈合增强的概念验证
我们的高强度离子电渗抗生素输送装置的功效。促进慢性伤口愈合
我们的设备所实现的功能将大大提高患者的生活质量,并降低整体医疗成本。
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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Jingwei Xie其他文献
Jingwei Xie的其他文献
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{{ truncateString('Jingwei Xie', 18)}}的其他基金
Multifunctional Intelligent Hierarchical Fibrous Biomaterials Integrated with Multimodal Biosensing and Feedback-Based Interventions for Healing Infected Chronic Wounds
多功能智能分层纤维生物材料与多模式生物传感和基于反馈的干预措施相结合,用于治愈感染的慢性伤口
- 批准号:
10861531 - 财政年份:2023
- 资助金额:
$ 16.41万 - 项目类别:
Strategies to Enhance Engineered Heart Tissue Based Myocardial Repair
增强基于工程心脏组织的心肌修复的策略
- 批准号:
10581419 - 财政年份:2023
- 资助金额:
$ 16.41万 - 项目类别:
A Novel High-Intensity Iontophoresis-Based Antibiotic Delivery Device for Efficacious Eradication of Chronic Wound Biofilms
一种新型高强度离子电渗疗法抗生素输送装置,可有效根除慢性伤口生物膜
- 批准号:
10634602 - 财政年份:2022
- 资助金额:
$ 16.41万 - 项目类别:
Biomimetic and Injectable Highly Porous Nanofiber Microsphere-based Platform for Alveolar Bone Regeneration
用于牙槽骨再生的仿生和可注射高孔隙纳米纤维微球平台
- 批准号:
10641000 - 财政年份:2022
- 资助金额:
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Engineering structural bone allografts for enhanced repair and reconstruction
工程结构同种异体骨移植以增强修复和重建
- 批准号:
9978190 - 财政年份:2020
- 资助金额:
$ 16.41万 - 项目类别:
Nanofiber-based Delivery of Combined Immune-modulating Compounds to Minimize Infection and Enhance Wound Healing
基于纳米纤维的组合免疫调节化合物的递送以最大程度地减少感染并促进伤口愈合
- 批准号:
10473866 - 财政年份:2017
- 资助金额:
$ 16.41万 - 项目类别:
Nanofiber-based Delivery of Combined Immune-modulating Compounds to Minimize Infection and Enhance Wound Healing
基于纳米纤维的组合免疫调节化合物的递送以最大程度地减少感染并促进伤口愈合
- 批准号:
10653967 - 财政年份:2017
- 资助金额:
$ 16.41万 - 项目类别:
Nanofiber-based Delivery of Combined Immune-modulating Compounds to Minimize Infection and Enhance Wound Healing
基于纳米纤维的组合免疫调节化合物的递送以最大程度地减少感染并促进伤口愈合
- 批准号:
10299094 - 财政年份:2017
- 资助金额:
$ 16.41万 - 项目类别:
Nanofiber-based Delivery of Combined Immune-modulating Compounds to Minimize Infection and Enhance Wound Healing
基于纳米纤维的组合免疫调节化合物的递送以最大程度地减少感染并促进伤口愈合
- 批准号:
10796228 - 财政年份:2017
- 资助金额:
$ 16.41万 - 项目类别:
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