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.

项目摘要/摘要： 语音障碍是一生中最常见的沟通障碍之一。大约3- 9%的总人口，包括儿童和成人，在任何给定的时间点都有声音问题。我们的 最终目标是使用注射或打印的方法永久修复受损、改变或功能障碍的声带组织 用于特定病变应用的生物材料。许多以前关于用于室颤修复的可注射生物材料的工作已经 通过针对准上皮下注射。这种递送方法对于外科治疗是有用的。 允许针头注射到原生LP或肌肉中进行室颤调节的病理。我们有 开发了具有生物活性的复合组织工程生物材料，即乙二醇壳聚糖(GCS)水凝胶 嵌入的胶原纤维(Col I+III)。在过去的一年里，我们的团队改进了GCS的组成 水凝胶转变为高孔性粘弹性水凝胶(PVH)。PVH增加的孔隙率有望增强 宿主细胞的渗透和存活，从而加速内源组织的再生。我们已经完成了一个 使用注射形式的PVH进行的一系列体外实验。 我们建议建立新的生物打印工具，可以将生物材料运送到现场包扎伤口。当大的时候 像癌症这样的病变是用冷刀或激光手术切除的，可能会产生巨大的空洞。 从腰椎到肌肉。能够快速就地固化、粘接和密封的新型材料将是 开发的目的是防止被排出和吸入呼吸道。我们提出了一种快速聚合材料， PVH-PRT，可以在几秒钟内治愈，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、粘接强度高、固化速度快的新材料。 我们将研究使用添加剂制造工具放置此类植入物的策略，这些工具基于 微流体学。我们将测试定制的内窥镜大小的外科“3D打印笔”使用体外喉和 VF复制品。我们将使用动物模型在体内对这一新概念进行初步研究。 我们将在兔子身上评估我们的生物材料。异物反应、组织粘弹性和发音 功能将分别通过组织学、力学测试和流动台实验进行评估。至 补充动物研究的已知局限性，并在先前研究的基础上，建立一个仿音生物反应器 将用于系统地改变支架的属性、类型和发声条件，并评估 工程化固有层的力学特性。我们的首要目标是将这些新的 生物材料和生物打印工具在未来5年内进入美国和加拿大的耳鼻喉科诊所 好几年了。