Ultrafast Laser Phonosurgery for Biomaterial Localization in Scarred Vocal Folds

超快激光声外科手术用于疤痕声带生物材料定位

• 批准号: 9751242
• 负责人: ADELA BEN-YAKAR
• 金额: $ 49.61万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751242
• 关键词: Ablation; Address; Affect; Air; American; Animal Model; Animals; Area; Biocompatible Materials; Biocompatible Materials Testing; Canis familiaris; Cheek structure; Cicatrix; Clinic; Clinical; Clinical Data; Collagen; Coupled; Custom; Data; Development; Dysphonia; Educational process of instructing; Endoscopy; Epithelial; Fiber; Fibrosis; Geometry; Goals; Hamsters; Human; Hyaluronic Acid; Hydrogels; Image; Image Analysis; Impairment; Inflammation; Injectable; Injections; Lamina Propria; Laryngoscopes; Larynx; Laser Surgery; Lasers; Location; Methods; Microscope; Microscopy; Modeling; Morphology; Occupations; Operative Surgical Procedures; Optics; Outcome; Patients; Performance; Phonation; Physiologic pulse; Polyethylene Glycols; Preclinical Testing; Property; Resistance; Site; Speed; Surface; Techniques; Technology; Testing; Tissue Differentiation; Tissues; Translating; Voice; Voice Disorders; Work; Wound Healing; base; clinical development; common treatment; design; ergonomics; experimental study; flexibility; functional improvement; healing; image guided; image processing; imaging capabilities; improved; in vivo; in vivo Model; innovation; miniaturize; optical fiber; optical imaging; optimal treatments; pre-clinical; pressure; prevent; prototype; response; response to injury; success; tool; vibration; viscoelasticity; visual feedback; vocal cord

Vocal fold scarring is a major cause of voice disorders like dysphonia, affecting an estimated 2 to 6 million people in the US alone. Vocal fold scarring results from the replacement of the vibratory superficial lamina propria (SLP) with stiff collagenous scar tissue. The modified viscoelastic properties of the SLP impairs vocal fold’s vibration and results in poor phonation. Over the last decade, injectable biomaterials have been investigated as a means to restore the viscoelasticity of scarred vocal folds. Unfortunately, poor localization due to increased resistance of biomaterial flow in stiff scar tissue adversely affects repeatable and reliable outcomes. To address this critical issue, we hypothesize that voids created by ultrafast laser pulses focused below the surface at the scar site will aid biomaterial injection and localization in the desired location. We base our hypothesis on a) the unique ability of ultrafast lasers to non-invasively create sub-surface cuts in bulk tissue, b) the fact that biomaterials preferentially flow through the path of least resistance, c) ex vivo experiments that resulted in reduced injection pressures and successful biomaterial localization in voids created by focused ultrafast laser pulses in scarred tissue, and d) Preliminary in vivo surgery experiments that resulted in long lasting biomaterial localization inside the ablated voids in healthy tissue with no detectable fibrosis (no scarring) around the void. To demonstrate the said hypothesis, we will develop larynx-specific, image guided ultrafast laser probes and test our surgery method in vivo using small (hamster) and large (canine) animal models. We will advance our goals in this project through three Specific Aims: 1) quantify the healing response of tissue to ultrafast laser ablation and characterize the void formation and biomaterial injection techniques in vivo in scar tissues using a table-top microscope and a proven hamster cheek pouch scar model, 2) design and develop larynx-specific ultrafast laser surgery probes that will be capable of sub-surface ablation in large animals (and eventually in human patients) and provide visual feedback and guidance through non-linear microscopy, and 3) evaluate the efficacy and ergonomics of the laser probes in a canine vocal fold scar model in vivo to ultimately assess the impact of localization of injected biomaterials on the functional improvement of vocal folds. Successful completion of the project will result in a new pre-clinically tested surgery tool that will enable controlled and repeatable testing of injectable biomaterials for the treatment of scarred vocal folds in human patients. This highly interdisciplinary project will provide innovations in achromatic, miniaturized optics, micro- manufacturing, large air-core optical fiber technologies for ultrafast laser delivery and non-linear endoscopy, high speed videostroboscopy image analysis and quantitative analysis methods for differentiating tissue morphologies using non-linear microscopy.

声带疤痕是导致发声困难等声音障碍的主要原因，估计影响 2 至 600 万人 仅在美国，声带疤痕是由振动固有层浅层 (SLP) 置换引起的。 具有僵硬的胶原疤痕组织的 SLP 的粘弹性特性会损害声带的振动。 在过去的十年里，人们对可注射生物材料进行了研究。 不幸的是，由于阻力增加，定位不良。 僵硬疤痕组织中生物材料的流动会对可重复和可靠的结果产生不利影响。 为了解决这个关键问题，我们勇敢地面对超快激光脉冲在聚焦下方产生的空隙。 疤痕部位的表面将有助于生物材料注射和定位在所需位置。 假设 a) 超快激光在大块组织中非侵入性地产生亚表面切割的独特能力，b) 事实上，生物材料优先流过阻力最小的路径，c) 离体实验 导致注射压力降低，并成功地将生物材料定位在由聚焦产生的空隙中 疤痕组织中的超快激光脉冲，以及 d) 初步的体内手术实验，产生了持久的效果 生物材料定位在健康组织的消融空隙内，周围没有可检测到的纤维化（无疤痕） 为了证明上述假设，我们将开发喉部特异性的图像引导超快激光探头。 并使用小型（仓鼠）和大型（犬）动物模型在体内测试我们的手术方法。 我们将通过三个具体目标推进我们在该项目中的目标：1）量化治疗反应 组织超快激光消融并表征体内空隙形成和生物材料注射技术 使用台式显微镜和经过验证的仓鼠颊囊疤痕模型在疤痕组织中，2) 设计和 开发喉部特异性超快激光手术探针，能够对大型动物进行表面下消融 （最终在人类患者中）并通过非线性显微镜提供视觉反馈和指导， 3) 评估激光探针在犬声带疤痕体内模型中的功效和人体工程学 最终评估注射生物材料的定位对声带功能改善的影响。 该项目的成功完成将产生一种新的临床前测试手术工具，该工具将能够实现受控 用于治疗人类患者疤痕声带的可注射生物材料的可重复测试。 这个高度跨学科的项目将在消色差、微型光学、微光学等领域提供创新。 制造、用于超快激光传输和非线性内窥镜的大型空芯光纤技术、高 用于区分组织的高速视频频闪图像分析和定量分析方法 使用非线性显微镜观察形态。