Bioprintable composite materials and microfluidic tools for vocal fold restoration and repair

用于声带修复和修复的生物打印复合材料和微流体工具

• 批准号: 10543434
• 负责人: LUC MONGEAU
• 金额: $ 49.26万
• 依托单位: MCGILL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10543434
• 关键词: 3D Print; Acceleration; Acoustics; Adhesions; Adhesives; Adult; Animal Model; Animals; Atomic Force Microscopy; Benign; Biocompatible Materials; Biological; Bioreactors; Canada; Cells; Characteristics; Chemicals; Chemistry; Child; Clinic; Collagen; Collagen Fiber; Communication impairment; Complement; Custom; Deposition; Devices; Dysphonia; Elastin; Endoscopy; Engineering; Epithelium; Excision; Extracellular Matrix; Foreign Bodies; Gel; General Population; Goals; Grant; Head and neck structure; Histology; Hoarseness; Human; Hydrogels; Image; Image Analysis; Immune response; Immunohistochemistry; Implant; In Situ; In Vitro; Incubators; Infiltration; Ingestion; Injectable; Injections; Injury; Lamina Propria; Laryngoscopes; Larynx; Laser Scanning Microscopy; Lasers; Legal patent; Lesion; Location; Longevity; Magnetic Resonance Imaging; Malignant - descriptor; Measurement; Mechanics; Medial; Methods; Microfluidics; Morphology; Muscle; Natural regeneration; Needles; Operative Surgical Procedures; Optics; Oryctolagus cuniculus; Otolaryngology; Outcome Study; Oxygen; Pathology; Patients; Performance; Permeability; Phonation; Pilot Projects; Polymers; Porosity; Printing; Production; Property; Resected; Rheology; Series; Site; Speed; Surgical Injuries; Surgical Models; Testing; Time; Tissue Engineering; Tissues; Translating; United States; Voice; Voice Disorders; Work; bioprinting; cancer surgery; clinical translation; cytotoxicity; design; experimental study; fabrication; glycol-chitosan; healing; in vivo; in vivo evaluation; injury and repair; manufacture; novel; nutrition; polymerization; prevent; prophylactic; reconstruction; repaired; response; restoration; scaffold; seal; tissue regeneration; tool; viscoelasticity; vocal cord; wound; wound dressing

PROJECT SUMMARY/ABSTRACT: Voice disorders are among the most common communication disorders across the lifespan. Approximately 3- 9% of the general population, including children and adults, have a voice problem at any given point in time. Our ultimate aim is the permanent repair of injured, altered or dysfunctional vocal fold tissue using injected or printed biomaterials for lesion-specific application. Much previous work on injectable biomaterials for VF repair has targeted sub-epithelial injections through a needle. Such delivery method is useful for the surgical treatment of pathologies allowing needle injection into the native LP, or into the muscle for VF medialization. We have developed composite bioactive tissue-engineered biomaterials, namely glycol-chitosan (GCS) hydrogels with imbedded collagen fibers (COL I+III. Within the past year, our group has refined the composition of the GCS hydrogel to a highly porous viscoelastic hydrogel (PVH). The increased porosity of PVH is expected to enhance infiltration and survival of host cells and thus accelerate endogenous tissue regeneration. We have completed a series of in vitro experiments using an injectable form of PVH. We propose to build novel bioprinting tools that can deliver biomaterials to dress wounds on site. When large lesions such as cancer are surgically removed using cold knifes or lasers, large voids are created possibly all the way through the LP, down to the muscle. Novel materials that cure, adhere and seal quickly in situ will be developed to prevent being dislodged and ingested into the airway. We propose a fast polymerization material, PVH-prt, that cures in seconds, as opposed to minutes, and that can be printed on site through a laryngoscope using needle-sized nozzles. On-site layer-by-layer deposition and sculpting would rebuild the resected portion of the VF using new materials that are mechanically tough, with high adhesive strength, and that solidify quickly. We will investigate strategies to lay such implants using additive manufacturing tools that are based on microfluidics. We will test custom-made endoscopic size surgical “3D printing pens” using ex vivo larynges and VF replicas. We will perform pilot studies of this novel concept in vivo using an animal model. We will evaluate our biomaterials in rabbits. Foreign body response, tissue viscoelasticity and phonatory functions will be evaluated with histology, mechanical tests and flow-bench experiments, respectively. To complement the known limitations of animal studies and build on previous studies, a phonomimetic bioreactor will be used to systematically vary scaffold properties, types and phonation conditions, and assess the mechanical characteristics of the engineered lamina propria. Our overarching goal is to translate these new biomaterials and bioprinting tools into otolaryngology clinics in the United States and Canada within the next 5 years.

项目概要/摘要： 声音障碍是一生中最常见的沟通障碍之一。 9% 的普通人群，包括儿童和成人，在任何特定时间点都存在声音问题。 最终目标是使用注射或打印技术永久修复受伤、改变或功能失调的声带组织 用于特定病变应用的生物材料之前有很多关于用于 VF 修复的可注射生物材料的工作。 通过针进行靶向上皮下注射，这种输送方法可用于手术治疗。 我们有允许将针注射到天然 LP 或肌肉中进行 VF 内侧化的病理学。 开发了复合生物活性组织工程生物材料，即乙二醇壳聚糖（GCS）水凝胶 嵌入胶原纤维（COL I+III）。在过去的一年里，我们组改进了GCS的成分 水凝胶转变为高水多孔粘弹性凝胶（PVH）PVH 的孔隙率增加预计会增强。 宿主细胞的浸润和存活，从而加速内源性组织再生。 使用可注射形式的 PVH 进行的一系列体外实验。 我们建议建造新型生物打印工具，可以在伤口较大时提供生物材料来包扎伤口。 使用冷刀或激光通过手术切除癌症等病变，可能会产生大的空隙 穿过 LP 直至肌肉的新型材料将在原位快速固化、粘附和密封。 我们开发了一种快速聚合材料，以防止脱落和摄入气道。 PVH-prt，在几秒钟内固化，而不是几分钟，并且可以通过喉镜现场打印 使用针头大小的喷嘴现场逐层沉积和雕刻将重建切除的部分。 VF 采用机械坚韧、粘合强度高且固化速度快的新材料。 我们将研究使用基于增材制造工具的植入物的策略 我们将使用离体喉部和微流体技术来测试定制的内窥镜尺寸的手术“3D 打印笔”。 VF 复制品。我们将使用动物模型对这一新颖概念进行体内试验研究。 我们将在兔子身上评估我们的生物材料的异物反应、组织粘弹性和发声能力。 将分别通过组织学、机械测试和流动台实验来评估功能。 补充动物研究的已知局限性，并以先前的研究为基础，拟音生物反应器 将用于系统地改变支架特性、类型和发声条件，并评估 我们的首要目标是转化这些新的工程固有层的机械特性。 未来 5 年内将生物材料和生物打印工具引入美国和加拿大的耳鼻喉科诊所 年。