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：将生物刺激植入物用于声门型喉癌的长期治疗 不足 摘要 声门闭合不全（GI）是一种喉部疾病，可损害沟通和吞咽 声带麻痹、老年喉、外伤、手术或放射线导致的功能障碍。最常见的 GI的治疗是使用临时纳米多孔生物材料进行声带增强， 声门闭合然而，目前可用的材料很难恢复生物力学性能， 天然声带，可以与密集的组织细胞反应，而只有持续三个 到十八个月。此外，声带是一个复杂的层状组织能够产生声音 这是由于细胞外基质和细胞组分的特定机械性质。然而，在这方面， 声带增大的结构、细胞和内在机械效应尚未被 充分表征，特别是在原位实现体内平衡之后。需要一口井 特征化和有目的地设计的可注射植入物， 而不产生炎症或损害声带柔韧性。为了满足这一需求， 我们开发了一种新的微孔退火颗粒（MAP）支架， 生物力学匹配声带，能够促进组织整合，并提供 持久的组织块。该提案旨在（1）开发MAP相关的从头检测方法， 组织形成，（2）表征体内递送的临床可行性，（3）确定 毒理学特征和（4）启动MAP水凝胶声带的首次人体临床试验 增强