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.

项目概要/摘要大约每 2000 名儿童中就有 1 名出生时患有先天性气道畸形，其他儿童则患有气管畸形由于疾病或创伤造成的缺陷；这些患者中的一个重要部分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源自超过 75 年的研究气管替代物的开发，但仍然需要针对患者特定且适合的气管移植物可以提供长期、免干预的治疗，同时与患者一起成长。本次研究的目的该奖学金的目的是设计一种针对患者的 3D 生物打印胶原蛋白气管移植物，以重现机械通过结合仿生微观结构来模拟天然气管的特性。 3D生物打印是一种理想的技术适合应对这一挑战，因为它允许我们使用天然生物材料，如 I 型胶原蛋白和脱细胞气管 ECM，构建与患者解剖结构完全匹配的移植物。范伯格实验室有开发了新一代自由形式可逆嵌入悬浮水凝胶（FRESH）生物打印这将使我能够控制打印支架的微观结构以复制细胞外基质原生气管中发现的组织。使用 3D 将区域气管力学与生理负荷相匹配图案化的仿生微观结构，该提案将朝着耐用的、针对患者的、长段气管缺损的免免疫抑制治疗。在第一个目标中，我将使用高分辨率体积成像来询问天然气管细胞外基质微观结构。这些数据集将被使用为气管的不同部分设计适合区域的仿生微结构（例如环、结缔组织）。这些微观结构模式有望重现生理力学有限元分析 (FEA) 模型和 3D 生物打印胶原蛋白结构的特性。在第二个目标中我将使用特定年龄的气管测量数据和去识别化的医学成像数据集来生成患者- 使用开源成像分割工具特定的儿科气管移植物几何形状。地区性的适当的仿生微观结构将在这些移植物几何形状中形成图案。这些仿生气管移植物将在 FEA 中建模，然后用胶原蛋白打印并进行机械表征（例如，塌陷力、顺应性、可缝合性）以展示生理学上必需的天然物质的重演气管力学。为了完成这项研究，我组建了一个在以下领域拥有丰富专业知识的团队：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过制定严格的培训计划，利用卡内基梅隆大学的世界一流环境大学和匹兹堡大学帮助我建立必要的技术和专业技能一位多产的医师科学家。这个提案将启动我研究再生的长期目标，用于治疗先天性、创伤性和肿瘤性头颈部组织缺陷的功能性组织支架同时担任耳鼻喉科医师，专攻头颈外科。