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

• 批准号: 9238202
• 负责人: Mariah S Hahn
• 金额: $ 10万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 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/9238202
• 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; Engineering; Environment; Evaluation; Extracellular Matrix; Family suidae; Fibroblasts; Filler; Formulation; 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

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.

描述（由申请人提供）：声带疤痕是一种虚弱的条件，证明很难用当前的手术技术或标准注射填充剂来治疗。我们的漫长 术语的目的是设计可促进伤口修复并诱导组织再生的可注射产品，以治疗慢性人声折叠疤痕和其他细胞外基质（ECM）的缺陷。该建议旨在利用植入物质的能力调节入侵巨噬细胞和声带褶皱成纤维细胞的表型，以改善慢性人声折叠疤痕的恢复。我们将开发基于PEGDA的可注射水凝胶，该水凝胶将与先前鉴定为抗纤维化和/或免疫调节性的细胞因子共轭。我们的工作假设是，这些PEGDA细胞因子水凝胶将能够将慢性疤痕中发现的肌纤维细胞转移到正常的人声褶皱成纤维细胞表型，与正常的人声折叠层层粘膜层结构和功能相关。我们进一步假设，在我们发达的水凝胶的存在下，对于慢性声折叠疤痕恢复不良的经典活化表型将被修改为抗炎表型。我们将采用系统化学，体外细胞2D/3D单/CO培养研究，体内和体内研究的独特组合，以解决细胞生物材料特征之间的复杂相互作用，并影响细胞行为，生物力学和手术必需品，以创建合适的临床结果。我们的发现将为操纵慢性声带疤痕表型提供必要的基础工作，以此作为促进声带功能快速，完全恢复的一种机制。