Translating a biostimulatory implant for the long-term treatment of glottic insufficiency

将生物刺激植入物用于声门功能不全的长期治疗

• 批准号: 10650269
• 负责人: James J. Daniero
• 金额: $ 60.06万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10650269
• 关键词: Accidents; Acute; Address; Adverse event; Biocompatible Materials; Biological; Biological Assay; Biomechanics; Cadaver; Cells; Characteristics; Clinical; Clinical Research; Clinical Trials; Communication impairment; Complex; Cytometry; Deglutition; Evaluation; Extracellular Matrix; Fingerprint; Functional disorder; Gel; Goals; Good Manufacturing Process; Homeostasis; Human; Hydrogels; Hypersensitivity; Immobilization; Implant; In Situ; Inflammation; Injectable; Injections; Intramuscular; Laryngeal Diseases; Larynx; Mechanics; Methods; Modeling; Modulus; Molecular; Nanoporous; Operative Surgical Procedures; Paralysed; Phase; Pilot Projects; Pliability; Porosity; Positioning Attribute; Pre-Clinical Model; Property; Radiation; Raman Spectrum Analysis; Retrieval; Safety; Secure; Testing; Time; Tissues; Titrations; Toxic effect; Toxicology; Translating; Trauma; Voice; common treatment; cytotoxicity; design; ergonomics; first-in-human; genotoxicity; high dimensionality; histiocyte; implantation; improved; in vivo; indexing; mechanical properties; nanoindentation; novel; particle; pre-clinical; research clinical testing; response; scaffold; standard of care; success; systemic toxicity; technology development; translational potential; vocal cord

RFA-DC-22-001: Translating a biostimulatory implant for the long-term treatment of glottic insufficiency Abstract Glottic insufficiency (GI) is a laryngeal disorder that can impair communication and swallowing function due to vocal fold paralysis, presbylarynges, trauma, surgery, or radiation. The most common treatment for GI is vocal fold augmentation with temporary nanoporous biomaterials that assist with glottic closure. However, currently available materials poorly restore the biomechanical properties of the native vocal fold and can be associated with dense histiocytic responses, while only lasting three to eighteen months. In addition, vocal folds are a complex laminar tissue capable of producing voice due to specific mechanical properties of the extracellular matrix and cellular components. However, the structural, cellular, and intrinsic mechanical effects of vocal fold augmentation have not yet been fully characterized, particularly after achieving homeostasis in situ. There is a need for a well characterized and purposefully-designed injectable implant that can restore permanent laryngeal function without producing inflammation or compromising vocal fold pliability. To address this need, we developed a novel iteration of microporous annealed particle (MAP) scaffold that is biomechanically matched to the vocal fold, capable of promoting tissue integration, and providing persistent tissue bulk. This proposal aims to (1) develop assays of MAP-associated de novo tissue formation, (2) characterize the clinical feasibility of in vivo delivery, (3) determine the toxicology profile and (4) initiate a first-in-human clinical trial of MAP hydrogel vocal fold augmentation.

RFA-DC-22-001：翻译生物刺激性植入物，用于长期治疗发光 不足 抽象的 鼻孔功能不全（GI）是一种喉部疾病，可能会损害沟通和吞咽 由于声带瘫痪，长老会，创伤，手术或辐射引起的功能。最常见的 GI的治疗是通过临时纳米多孔生物材料进行声带增强 闭合。但是，目前可用的材料恢复了很差的生物力学特性 天然声带，可以与密集的组织细胞反应相关联，而仅持续三个 到十八个月。此外，声带是一种能够产生声音的复杂层状组织 由于细胞外基质和细胞成分的特定机械性能。然而， 声带增强的结构，细胞和内在的机械效应尚未 充分表征，特别是在原位实现体内平衡之后。需要井 特征和有目的设计的可注射植入物，可以恢复永久性喉 功能而无需产生炎症或损害声带柔韧性。为了满足这种需求， 我们开发了一种新颖的微孔退火粒子（MAP）支架的迭代 生物力学与声带匹配，能够促进组织整合并提供 持续的组织散装。该建议旨在（1）开发与从头相关的de Novo的测定 组织形成，（2）表征体内递送的临床可行性，（3）确定 毒理学概况和（4）启动MAP水凝胶声折的首次人类临床试验 增强。