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; 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： 语音障碍是整个生命周期中最常见的沟通障碍之一。大约3- 包括儿童和成人在内的普通人群中有9％在任何给定的时间点都有语音问题。我们的 最终目标是使用注射或印刷的受伤，改变或功能失调的声带组织的永久修复 用于病变特异性应用的生物材料。关于VF维修的可注射生物材料的许多以前的工作已有 通过针对针对的靶向下皮注射。这种输送方法对于手术治疗很有用 允许针头注射针对天然LP的病理或肌肉进行VF内侧化。我们有 开发了复合生物活性组织工程生物材料，即与甘体 - 吉他式（GCS）水凝胶一起 嵌入的胶原蛋白纤维（Col I+III。在过去的一年中，我们的小组完善了GC的组成 水凝胶至高度多孔的粘弹性水凝胶（PVH）。 PVH的孔隙率提高有望增强 宿主细胞的浸润和存活，从而加速内源性组织再生。我们已经完成了 使用可注射形式的PVH形式的一系列体外实验。 我们建议建立新型的生物打印工具，这些工具可以提供生物材料在现场打扮的伤口。大 使用冷针或激光器通过手术切除等病变，创建大量空隙 穿过LP的方式，一直到肌肉。治愈，粘附和密封的新颖材料将是原位的 开发的目的是防止被移出并摄入气道。我们提出了一种快速的聚合材料， PVH-prt（在几分钟内都可以在几秒钟内治愈，并且可以通过喉镜在现场打印 使用针大小的喷嘴。现场逐层沉积和雕刻将重建切除的部分 使用机械强度，具有较高粘合力的新材料的VF，并迅速固化。 我们将使用基于基于的增材制造工具来调查以下策略 微流体学。我们将使用Ex Vivo Larynges和 VF复制品。我们将使用动物模型在体内对这种新颖概念进行试验研究。 我们将评估兔子的生物材料。异物反应，组织粘弹性和摄影 功能将分别通过组织学，机械测试和流台实验评估。到 补充动物研究的已知局限性并在先前的研究基础上建立，这是一种具有指的生物反应器 将用于系统地改变脚手架特性，类型和发音条件，并评估 工程性椎板的机械特性。我们的总体目标是翻译这些新的 在接下来的5个 年。