3D Printed Collagen Tracheal Scaffolds with Biomimetic Microstructure

具有仿生微结构的 3D 打印胶原蛋白气管支架

基本信息

批准号：
10475263
负责人：
Joshua Tashman
金额：
$ 3.2万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10475263
关键词：
3-Dimensional 3D Print Adolescent Adult Age Allografting Anatomy Biocompatible Materials Biological Biomechanics Biomimetics Breathing Child Childhood Collagen Collagen Type I Connective Tissue Data Data Set Defect Development Developmental Biology Disease Engineering Environment Extracellular Matrix Extracellular Matrix Proteins Family suidae Fellowship Fiber Filament Finite Element Analysis Foundations Generations Geometry Goals Head and Neck Surgery Head and neck structure Human body Hydrogels Image Immunosuppression Individual Intervention Malignant Neoplasms Measurement Measures Mechanics Medical Imaging Microscopy Modeling Motion Natural regeneration Operative Surgical Procedures Optical Coherence Tomography Otolaryngologist Patients Pattern Physicians Physiological Printing Property Research Resolution Scientist Solid Source Specificity Stress Structure Surface Surgical sutures Techniques Technology Testing Tissue Engineering Tissues Trachea Training Transplantation Trauma Universities Variant Vascularization Work X-Ray Computed Tomography airway epithelium base biofabrication bioprinting clinically relevant design imaging Segmentation implantation improved innovation malformation mechanical load mechanical properties microCT neglect open source patient subsets pediatric patients pressure regenerative respiratory restenosis scaffold second harmonic success tissue support frame tool

项目摘要

PROJECT SUMMARY/ABSTRACT Approximately 1 in 2000 children are born with a congenital airway malformation and others develop tracheal defects due to disease or trauma; an important subset of these patients needs a tracheal graft to regain airway patency. Many impactful discoveries and innovative strategies have resulted from over 75 years of research into development of a tracheal replacement, but there remains a need for a tracheal graft that is patient-specific and can provide long-term, intervention free treatment while growing with the patient. The research goal of this fellowship is to engineer a patient-specific, 3D bioprinted collagen tracheal graft that recapitulates the mechanical properties of native trachea by incorporating biomimetic microstructure. 3D bioprinting is a technology ideally suited for tackling this challenge, as it allows us to use native biological materials, like collagen type I and decellularized tracheal ECM, to construct grafts that exactly match patient anatomy. The Feinberg lab has developed a new generation of Freeform Reversible Embedding of Suspended Hydrogels (FRESH) bioprinting that will allow me to control the microstructure of printed scaffolds to reproduce the extracellular matrix organization found in native trachea. By matching regional tracheal mechanics to physiologic loading using 3D patterned biomimetic microstructure, this proposal will take an important step towards a durable, patient-specific, immunosuppression free treatment for long-segment tracheal defects. In the first aim I will use high resolution volumetric imaging to interrogate native tracheal extracellular matrix microstructure. These data sets will be used to design regionally appropriate biomimetic microstructures for different sections of the trachea (e.g. ring, connective tissue). These microstructural patterns are expected to recapitulate physiologic mechanical properties in both finite element analysis (FEA) models and 3D bioprinted collagen constructs. In the second aim I will use age-specific tracheal measurement data and deidentified medical imaging datasets to produce patient- specific pediatric tracheal graft geometries using open-source imaging segmentation tools. Regionally appropriate biomimetic microstructure will be patterned throughout these graft geometries. These biomimetic tracheal grafts will be modelled in FEA and then printed in collagen and mechanically characterized (e.g. collapsing forces, compliance, suturability) to demonstrate recapitulation of physiologically essential native tracheal mechanics. To accomplish this research, I have assembled a team with significant expertise in biomechanics, developmental biology, tissue engineering, and extracellular matrix. I have worked with this team to develop a rigorous training plan that will take advantage of the world class environment of Carnegie Mellon University and the University of Pittsburgh to help me build the technical and professional skillsets necessary for a productive physician-scientist. This proposal will jumpstart my long-term goals of investigating regenerative, functional tissue scaffolds for treatment of congenital, traumatic, and oncologic head and neck tissue defects while practicing as an otolaryngologist with a subspecialization in head and neck surgery.

项目摘要/摘要 2000年，大约有1个儿童出生时出现了先天性气道畸形，而其他儿童则出现气管由于疾病或创伤引起的缺陷；这些患者的重要子集需要气管移植物来恢复气道通畅。许多有影响力的发现和创新策略是由超过75年的研究产生的开发气管置换，但仍需要患者特异性的气管移植物可以在与患者一起生长的同时提供长期，无干预的治疗。这个研究目标奖学金是设计一种患者特异性的3D生物打印胶原蛋白气管移植物，该胶原蛋白移植物概括了机械通过合并仿生微结构的天然气管的性质。 3D生物打印是一项理想的技术适合应对这一挑战的适用脱细胞气管ECM，以构建与患者解剖结构完全匹配的移植物。 Feinberg实验室有开发了新一代的自由形式可逆嵌入悬浮水凝胶（新鲜）生物打印这将使我能够控制印刷脚手架的微观结构以重现细胞外基质在本地气管中发现的组织。通过将区域气管力学与生理负荷相匹配，使用3D 图案化的仿生微观结构，该建议将朝着耐用，特定于患者的耐用，特定于患者迈出一步长段气管缺陷的免疫抑制治疗。在第一个目标中，我将使用高分辨率体积成像以询问天然气管外基质微结构。这些数据集将使用为气管的不同切片设计区域性适当的仿生微结构（例如环，结缔组织）。这些微观结构模式有望概括生理机械有限元分析（FEA）模型和3D生物打印胶原蛋白构建体中的性质。在第二个目标我将使用特定年龄的气管测量数据和去识别的医学成像数据集来产生患者 - 使用开源成像分割工具的特定小儿气管移植几何形状。区域在这些移植几何形状中，将对适当的仿生微观结构进行图案。这些仿生气管移植物将以FEA进行建模，然后用胶原蛋白印刷并进行机械表征（例如，崩溃的力，合规性，辅助性）证明了生理上必不可少的天然的概括气管力学。为了完成这项研究，我组建了一个具有重要专业知识的团队生物力学，发育生物学，组织工程和细胞外基质。我曾与这个团队合作制定一项严格的培训计划，以利用卡内基·梅隆的世界一流环境大学和匹兹堡大学，以帮助我建立必要的技术和专业技能生产性医师科学家。该建议将使我长期调查再生目标，用于治疗先天性，创伤性和肿瘤学头和颈部组织缺陷的功能性组织支架在作为耳鼻喉科医生的耳鼻喉科医生中练习的同时，在颈部手术中进行了专业化。