Cardiopulmonary Organ Engineering

心肺器官工程

基本信息

批准号：
7270659
负责人：
WILLIAM R WAGNER
金额：
$ 118.8万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7270659
关键词：
Actins Acute Address Adhesions Adult Animal Model Animals Anisotropy Anticoagulation Aorta Area Arteries Arts Atherosclerosis Attention Autologous Beds Belief Biochemical Biocompatible Biocompatible Materials Biological Biology Biomechanics Biomedical Engineering Biopolymers Bioreactors Blood Blood Vessels Blood capillaries Bone Marrow Bone Marrow Cells CD34 Antigens CD34 gene Caliber Cardiac Cardiac Myocytes Cardiomyoplasty Cardiopulmonary Cardiopulmonary Bypass Cardiovascular Diseases Cardiovascular system Caring Cell Adhesion Cell Differentiation process Cell Separation Cell Survival Cell Transplantation Cells Cessation of life Characteristics Chemicals Chemistry Chronic Chronic lung disease Cicatrix Clinical Clonal Expansion Collagen Collagen Type I Condition Congestive Heart Failure Coronary Coronary Artery Bypass Coronary artery Coupling Cultured Cells Data Development Device Designs Devices Diagnosis Differentiation Antigens Diffusion Dorsal Echocardiography Edema Elastomers Electric Conductivity Embryo Endothelial Cells Endothelium Engineering Engraftment Ensure Environment Epitopes Evaluation Extracellular Protein Extracorporeal Membrane Oxygenation Family suidae Fiber Fibroblasts Gases Gel Generations Goals Growth Growth Factor Harvest Healthcare Heart Heart Diseases Heart Transplantation Heart failure Hematopoietic Hematopoietic stem cells Hemorrhage Heterogeneity Home environment Human Hyperplasia Hypertension Image Immunodeficient Mouse Implant In Situ In Vitro Individual Industry Infarction Infection Inflammatory Injection of therapeutic agent Injury Intercalated disc Interstitial Collagenase Investigation Ischemia Kidney Lasers Left Life Ligation Limb structure Location Lower Extremity Lung Marrow Mechanics Medial Membrane Mesenchymal Stem Cells Methodology Methods Microscopic Modeling Modification Molds Morphology Morus Motion Movement Mus Muscle Muscle Cells Myoblasts Myocardial Myocardial Infarction Myocardial Ischemia Myocardial perfusion Myocardial tissue Myocardium Myosin ATPase Natural regeneration Nature Necrosis Numbers Nutrient Omentum Operative Surgical Procedures Organ Organ failure Oryctolagus cuniculus Outcome Oxygen Oxygenators Paper Pathway interactions Patient Care Patients Pattern Perfusion Peripheral Permeability Pharmacologic Substance Phenotype Physiological Physiology Placement Polymer Chemistry Polymers Population Porosity Positioning Attribute Positron-Emission Tomography Postoperative Period Principal Investigator Procedures Process Property Proto-Oncogene Protein c-kit Protocols documentation Pump Rattus Reporting Research Research Personnel Risk Rodent Saphenous Vein Sea Seeds Series Signal Transduction Skeletal Muscle Skeletal Myoblasts Skeletal system Small Intestines Solutions Source Speed Staging Stem cells Stimulus Stress Stromal Cells Structure Submucosa Surface Surgeon Sus scrofa Syndrome Techniques Technology Testing Therapeutic Thrombosis Time Tissue Engineering Tissues Training Translating Translations Transplantation Transplanted tissue Trauma Tube Tubular formation Ultrasonography United Network for Organ Sharing United States Ursidae Family Vascular Endothelial Growth Factors Vascularization Vasomotor Veins Ventricular Virus Vision Week Work ameroid angiogenesis base blood oxygenator blood pump capillary carbon dioxide transport cell type cellular engineering clinical application clinically significant comparative conditioning day design desire elastomeric expectation experience fetal functional loss graft failure heart allograft heart function immunosuppressed implantation improved in vivo in vivo regeneration internal thoracic artery medical specialties migration model development mouse Smc1l1 protein mouse Smc1l2 protein novel older men precursor cell programs pulmonary function reconstruction repaired size soft tissue success vascular tissue engineering vasculogenesis ventricular assist device

项目摘要

DESCRIPTION (provided by applicant): The aim of this proposal is to design solutions for vascular, cardiac, and pulmonary organ failure by building interactive teams of researchers focused on specific aspects of cardiopulmonary organ engineering. Our efforts will encompass three projects: a tissue engineered blood vessel, a myocardial patch, and a biohybrid lung. The assembled research teams will function as cores of expertise that address common tasks associated with all three projects. Five research cores will be established in the following areas: 1) matrix synthesis and surface modification, 2) precursor cell isolation and characterization, 3) biomechanical testing and conditioning, 4) animal model development, and 5) construct assessment. For each of the three organ projects we have design objectives (Specific Aims) that will be achieved in the five-year period of proposed work: 1) Tissue engineered blood vessel - A biological blood vessel will be developed that achieves long-term potency in the rat model and is subsequently evaluated in the porcine model. The blood vessel will be a "biological equivalent" to autologous arteries from a mechanical and biofunctional perspective. During vessel development in vitro, specific mechanical training protocols that have been optimized to direct appropriate cell differentiation and expression of matrix components will be employed. 2) Myocardial patch - A process will be developed that allows the reconstruction of functional myocardium in ischemic or dysfunctional regions of the heart, This process will be characterized by the seeding of stem cells onto a bioerodible thermoplastic elastomer which has been designed to micromechanically transmit appropriate stresses to the stem cells during an in vitro seeding period and after placement within the diseased myocardium. Vascularization of this implanted construct will be achieved by surgical placement of omental tissue atop the placed myocardial patch. 3) Biohybrid lung - An oxygenator comprised of endothelialized microporous hollow fibers arranged in: plates and rotated to mix and pump the blood will serve as a biohyrid lung capable of providing gas exchange in a calf for 14 days. The hollow fibers will be surface modified to support the culture of autologous endothelial cells. The endothelial cells will act to reduce the anticoagulation requirements of the device while maintaining adequate fiber permeability.

描述（由申请人提供）：该提案的目的是通过建立针对心肺器官工程特定方面的研究人员的交互式研究团队来设计血管，心脏和肺部器官故障的解决方案。我们的努力将包括三个项目：组织工程血管，心肌斑块和生物杂化肺。组装的研究团队将充当专业知识的核心，以解决与所有三个项目相关的常见任务。将在以下区域中建立五个研究核心：1）基质合成和表面修饰，2）前体细胞分离和表征，3）生物力学测试和调节，4）动物模型开发，以及5）构造评估。对于三个器官项目中的每个项目，我们都有设计目标（特定目的），这些目标将在拟议的五年内实现：1）组织工程血管 - 将开发出生物血管，以实现长期的效力大鼠模型并随后在猪模型中评估。从机械和生物功能的角度来看，血管将是自体动脉的“生物学上”。在体外血管发育过程中，将采用已优化的特定机械训练方案，以指导基质组件的适当细胞分化和表达。 2）心肌斑 - 将开发一个过程，该过程允许在心脏的缺血性或功能失调区域重建功能性心肌，该过程的特征是干细胞的播种是在可生物适用的热塑性弹性体上的播种，该弹性剂旨在微机械旨在微机械传输适当的微机械传输在体外播种期间和在患病的心肌内放置后，对干细胞的压力。该植入构建体的血管形成将通过在放置的心肌斑块上的手术放置在手术上来实现。 3）生物杂化肺 - 一种充氧剂，由内皮化的微孔空心纤维组成：板和旋转以混合和泵送血液的氧化剂将作为能够在小牛中提供气体交换14天的生物hyriD肺。空心纤维将进行表面修饰，以支持自体内皮细胞的培养。内皮细胞将采取行动减少设备的抗凝要求，同时保持足够的纤维渗透性。

项目成果

期刊论文数量（31）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

In vivo performance of a phospholipid-coated bioerodable elastomeric graft for small-diameter vascular applications.

DOI：
10.1002/jbm.a.32997
发表时间：
2011-02
期刊：
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
影响因子：
4.9
作者：
Soletti, Lorenzo;Nieponice, Alejandro;Hong, Yi;Ye, Sang-Ho;Stankus, John J.;Wagner, William R.;Vorp, David A.
通讯作者：
Vorp, David A.

Biodegradable elastic patch plasty ameliorates left ventricular adverse remodeling after ischemia-reperfusion injury: a preclinical study of a porous polyurethane material in a porcine model.

DOI：
10.1016/j.jtcvs.2012.11.013
发表时间：
2013-08
期刊：
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
影响因子：
6
作者：
Hashizume, Ryotaro;Fujimoto, Kazuro L.;Hong, Yi;Guan, Jianjun;Toma, Catalin;Tobita, Kimimasa;Wagner, William R.
通讯作者：
Wagner, William R.

Tailoring the degradation kinetics of poly(ester carbonate urethane)urea thermoplastic elastomers for tissue engineering scaffolds.

DOI：
10.1016/j.biomaterials.2010.02.005
发表时间：
2010-05
期刊：
Biomaterials
影响因子：
14
作者：
Hong Y;Guan J;Fujimoto KL;Hashizume R;Pelinescu AL;Wagner WR
通讯作者：
Wagner WR

A small diameter, fibrous vascular conduit generated from a poly(ester urethane)urea and phospholipid polymer blend.

DOI：
10.1016/j.biomaterials.2009.01.013
发表时间：
2009-05
期刊：
BIOMATERIALS
影响因子：
14
作者：
Hong, Yi;Ye, Sang-Ho;Nieponice, Alejandro;Soletti, Lorenzo;Vorp, David A.;Wagner, William R.
通讯作者：
Wagner, William R.

Pericyte-based human tissue engineered vascular grafts.

DOI：
10.1016/j.biomaterials.2010.07.034
发表时间：
2010-11
期刊：
BIOMATERIALS
影响因子：
14
作者：
He, Wei;Nieponice, Alejandro;Soletti, Lorenzo;Hong, Yi;Gharaibeh, Burhan;Crisan, Mihaela;Usas, Arvydas;Peault, Bruno;Huard, Johnny;Wagner, William R.;Vorp, David A.
通讯作者：
Vorp, David A.