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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.

项目总结/文摘