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

基本信息

  • 批准号:
    10299094
  • 负责人:
  • 金额:
    $ 34.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-05-01 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

ABSRTACT Despite major efforts to keep operating rooms sterile, surgical site infections (SSIs) remain a serious and stub- born problem, killing up to 8,200 patients a year in the U.S. Our long-term goal is to develop novel therapies that effectively minimize risk of SSIs and promote wound healing. During the previous funding cycles of this award, we have demonstrated that i) successful encapsulation and sustained release of vitamin D and other immuno- modulating compounds induced higher cathelicidin antimicrobial peptide (CAMP) gene and protein (hCAP18/LL- 37) levels in immune cells and keratinocytes in cell culture, a human CAMP transgenic mouse wound model and human skin explants; ii) topical vitamin D increased killing of Staphylococcus aureus in a skin wound-infection model using our human CAMP transgenic mouse; and iii) exosomes secreted from immune cells treated with vitamin D contained higher levels of hCAP18/LL-37. Furthermore, we developed a novel gas-foaming expansion technique to fabricate improved 3D nanofiber scaffolds eluting vitamin D that promoted immune cell infiltration, induced hCAP18/LL-37, decreased inflammation, and promoted neovascularization and collagen deposition in human immune system-engrafted mice. Building on these findings, and our preliminary data, the goal of our proposal focuses on the development of nanofiber-based dressings for enhancing innate immunity. Our over- arching hypothesis is that co-encapsulating immunomodulating compounds with exosomes secreted from treated immune cells in 3D nanofiber scaffolds will synergistically enhance protection against SSIs and promote wound healing better than either component alone. To accomplish this, there are three specific aims: 1) Demon- strate efficient encapsulation and elution of immunomodulating compounds from our improved 3D nanofiber scaffolds; 2) Determine the antimicrobial and wound-healing efficacy of exosomes derived from primed or human CAMP transfected immune cells; and 3) Demonstrate the efficacy of immunomodulating compounds and exo- somes - co-incorporated 3D nanofiber scaffolds to promote healing and prevent infection in our humanized trans- genic mouse model and ex vivo human skin explants. Building on work from our prior grant, we expect successful completion of the aims in this renewal will lay a strong foundation for developing the next generation of novel therapeutic anti-infective wound dressings that could greatly speed healing, reduce rates of SSIs and minimize development of antibiotic resistance. We also expect these dressings could serve as effective treatments for traumatic and combat-related injuries.
ABSRTACT

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(3)

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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:
    $ 34.08万
  • 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:
    $ 34.08万
  • 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:
    10433163
  • 财政年份:
    2022
  • 资助金额:
    $ 34.08万
  • 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:
    $ 34.08万
  • 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:
    $ 34.08万
  • 项目类别:
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:
    $ 34.08万
  • 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:
    $ 34.08万
  • 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:
    $ 34.08万
  • 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:
    $ 34.08万
  • 项目类别:

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