3D Bioprinted Collagen Vascular Conduits For Use In Patients With Congenital Heart Defects

3D 生物打印胶原血管导管用于先天性心脏病患者

• 批准号: 10537817
• 负责人: Syed Faaz Ashraf
• 金额: $ 7.62万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10537817
• 关键词: 3-Dimensional; Anastomosis - action; Anatomy; Animal Model; Animals; Area; Autologous; Biomechanics; Biomedical Engineering; Bioreactors; Blood Vessels; Cardiac; Cells; Cellular Infiltration; Characteristics; Child; Clinical; Collagen; Common Ventricle; Complex; Computer Models; Congenital Abnormality; Congenital Heart Defects; Development; Electrospinning; Endothelium; Engineering; Extracellular Matrix; Foundations; Future; Geometry; Goals; Goretex; Growth; Histologic; Histology; Human; Hydrogels; Immunohistochemistry; Implant; Inferior vena cava structure; Inflammation; Lead; Liquid substance; MRI Scans; Measures; Mechanics; Methods; Modification; Monitor; Newborn Infant; Obstruction; Operative Surgical Procedures; Optical Coherence Tomography; Patients; Performance; Polyglycolic Acid; Porosity; Printing; Production; Property; Psychological reinforcement; Pulmonary artery structure; Rattus; Resistance; Resolution; Scientist; Specificity; Sprague-Dawley Rats; Stenosis; Surgeon; Testing; Thick; Thrombosis; Tissue Engineering; Tissue Viability; Tissues; Training; Tubular formation; Vascular Graft; Venous Pressure level; Work; base; biodegradable scaffold; biomaterial compatibility; biomechanical test; bioprinting; cost; design; hemodynamics; immunogenicity; implantation; improved; in vivo; mechanical properties; microCT; mouse model; pressure; scaffold; shear stress; simulation; tissue support frame; ultrasound; vascular tissue engineering

PROJECT SUMMARY/ABSTRACT Congenital heart defects (CHDs) are the most common birth defect in the US, with half of all newborns with CHD requiring surgical intervention. Surgical treatment of many CHDs involves implantation of synthetic conduits such as Gore-Tex™ due to their low cost, ease of surgical handling, and lack of alternatives. An example of this application is the extra-cardiac Fontan conduit for single ventricle anomalies, that connects the inferior vena cava to the pulmonary artery. Use of synthetic grafts as conduits in children, however, is complicated by progressive obstruction and lack of growth potential. Tissue engineered vascular grafts (TEVGs) are a potential solution, where a biodegradable scaffold with autologous cells mature into a functional blood vessel as the scaffold degrades. Recent work suggests that TEVG scaffold porosity is essential for cellular infiltration. Current TEVG production methods, however, are only able to produce simple tubular constructs that do not match the wide array of anatomies in children with CHDs. Patient specific Fontan conduits designed using Computational Fluid Dynamics (CFD) have been shown, in simulations, to improve their hemodynamic profile resulting in better flow distribution, improved energy efficiency and reduced wall shear stress. Thus, there remains critical need for patient specific conduits that are biocompatible and grow with the patient. The Feinberg lab has developed a 3D bioprinting platform called freeform reversible embedding of suspended hydrogels (FRESH) that enables printing of high-strength and microporous collagen-based ECM into functional, patient specific tissue scaffolds with unprecedented resolution (20 µm) and structural complexity. I hypothesize that the microporosity of FRESH printed, collagen-based, vascular conduits will drive in-vivo cellular infiltration and facilitate robust cellular remodeling towards neo-tissue formation, and that FRESH can produce conduits that meet the geometric demands required of children with CHD. In Aim 1 I will FRESH bioprint simple straight conduits, implant them into rats IVC and monitor their function as a conduit longitudinally via repeated in-vivo ultrasound. At pre- determined timepoints I will explant these TEVGs and assess the biomechanical and histological changes brought upon by in vivo cellular remodeling. In Aim 2 I will use computational modelling to determine wall shear stress on patient specific Fontan conduits, segmented from patients MRI scans, and reinforce areas of high wall shear stress by increasing regional or circumferential wall thickness. I will then FRESH 3D bioprint these patient specific Fontan conduits, gauge for accuracy and perform biomechanical tests on them. Completion of these aims is an important step towards our ability in creating patient specific, tissue engineered Fontan conduits that are suited to the array of anatomical geometries seen in patients with CHD, are modified with computational fluid dynamics to improve their long-term hemodynamic performance, are biocompatible and can grow with the patient. This work will allow us to move on to the next steps of large animal implantations of our TEVGs.

项目总结/文摘