Macrophage And Fibroblast Modulation Toward Chronic Vocal Fold Scar Restoration

巨噬细胞和成纤维细胞对慢性声带疤痕修复的调节

基本信息

批准号：
8841337
负责人：
Mariah S Hahn
金额：
$ 46.38万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8841337
关键词：
Affect American Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Basic Science Behavior Biocompatible Biocompatible Materials Biological Biological Assay Biomechanics Biomimetics Cells Characteristics Chemicals Chronic Cicatrix Clinical Clinical Trials Coculture Techniques Complex Connective Tissue Data Defect Disease Drug Formulations Engineering Environment Evaluation Extracellular Matrix Family suidae Fibroblasts Filler Future Gel Healed Health Heterogeneity Human Hydrogels Implant In Vitro Inflammatory Influentials Injectable Injury Invaded Knowledge Lamina Propria Maintenance Measures Mechanics Methods Modeling Modification Molecular Mono-S Myofibroblast Operative Surgical Procedures Outcome Pathway interactions Phenotype Phonation Population Production Property Research Signal Transduction Structure Techniques Testing Tissue Engineering Tissues Translations Voice Disorders Work Wound Healing base biomaterial development cell behavior cytokine design healing implant material implantation improved in vivo innovation macrophage next generation novel poly(ethylene glycol)diacrylate pressure regenerative repaired response restoration scaffold screening success tissue regeneration viscoelasticity vocal cord

项目摘要

DESCRIPTION (provided by applicant): Vocal fold scarring is a debilitation condition that has proven difficult to treat with current surgical techniques or standard injectable fillers. Our long term aim is to engineer injectable products that promote wound repair and induce tissue regeneration to treat chronic vocal fold scarring and other extracellular matrix (ECM) defects of the lamina propria. This proposal aims to harness the capacity of implanted materials to modulate the phenotype of invading macrophages and vocal fold fibroblasts toward achieving improved restoration of chronic vocal fold scar. We will develop PEGDA based injectable hydrogels that will be conjugated to cytokines previously identified as anti-fibrotic and/or immunomodulatory. Our working hypothesis is that these PEGDA cytokine hydrogels will be able to shift myofibroblasts found in chronic scar toward a normal vocal fold fibroblast phenotype associated with normal vocal fold lamina propria structure and function. We further hypothesize that the classically activated phenotype that is undesirable for chronic vocal fold scar restoration will be modified to an anti-inflammatory phenotype in the presence of our developed hydrogels. We will employ a unique combination of systematic chemical, in vitro cell 2D/3D mono/co culture studies, in vivo and ex vivo studies to resolve the complex interactions among cell biomaterial characteristics, and influences on cell behavior, biomechanics and the surgical requisites necessary to create a suitable clinical outcome. Our findings will provide the necessary ground work for manipulating chronic vocal fold scar phenotypes as a mechanism to promote rapid, complete restoration of vocal fold function.