Completely biological tissue-engineered pulmonic valve grown in vitro from human cells for pediatric patients

完全生物组织工程肺动脉瓣，由人体细胞在体外培养，供儿科患者使用

• 批准号: 10188591
• 负责人: ROBERT T TRANQUILLO
• 金额: $ 72.11万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188591
• 关键词: 3-Dimensional; Address; Adolescent; Adult; Animal Model; Area; Biochemical; Biological; Biological Assay; Caliber; Cardiac Surgery procedures; Cells; Cellularity; Child; Childhood; Clinical; Code; Commissure; Computer-Aided Design; Consensus; Data; Defect; Dimensions; Drops; Elements; Engineering; Ensure; Face; Failure; Fibroblasts; Funding; Geometry; Goals; Growth; Harvest; Heart Valves; Histology; Human; Immunohistochemistry; Implant; In Situ; In Vitro; Length; Liquid substance; Longitudinal Studies; Lung; Measurement; Measures; Modeling; Monitor; Outcomes Research; Patients; Performance; Phenotype; Physiologic pulse; Plant Roots; Positioning Attribute; Pre-Clinical Model; Preclinical Testing; Pulmonary artery structure; Pulmonary valve structure; Sheep; Site; Skin; Solid; Sterility; Stress; Structure; Surface; Surgical sutures; System; Systolic Pressure; Testing; Time; Tissue Engineering; Tissues; Translations; Tube; Ultrasonography; Validation; aortic valve; aortic valve disorder; aortic valve replacement; base; cardiac tissue engineering; clinically relevant; conditioning; design; experience; hemodynamics; implantation; lamb model; mechanical properties; novel; pediatric patients; pressure; shear stress; sheep model; success

Abstract The goal of this project is to create a heart valve that can grow with children and never require replacement. Using a biologically-engineered collagenous matrix in the form of a tube that has been shown to grow as a pulmonary artery replacement in lambs, and a novel design for a heart valve made from these tubes and degradable suture that confers durable commissures as well as valve growth potential, we will design, optimize, test, and implant tri-tube valves in a juvenile sheep model to demonstrate valve growth. Aim 1 will use computer-aided design (a fluid-structure interaction model for valve opening and finite element model for the closed valve state) to screen combinations of design parameters (defining coaptation area and geometry) for efficient valve function, Aim 2 will test the optimal designs in a pulse duplicator and validate/refine the CAD models, and Aim 3 will involve studies of the valve in growing juvenile sheep. Long-term studies of pulmonary and aortic valve replacement are designed with measurements to rigorously address valve growth.

摘要 该项目的目标是创造一种可以与儿童一起成长并且永远不需要更换的心脏瓣膜。 使用一种生物工程化的胶原基质，以一种管的形式，已经显示出作为一种细胞生长， 肺动脉置换术，以及由这些管制成的心脏瓣膜的新设计， 可降解缝线，赋予持久的连合以及瓣膜生长潜力，我们将设计， 在幼年绵羊模型中优化、测试和植入三管瓣膜，以证明瓣膜生长。目标1将 使用计算机辅助设计（阀门开启的流体-结构相互作用模型和 关闭的瓣膜状态）以筛选设计参数的组合（限定接合面积和几何形状） 为了有效地发挥阀门的功能，目标2将在脉冲复制器中测试最佳设计，并验证/改进计算机辅助设计 目标3将涉及在成长中的幼年绵羊中研究瓣膜。肺部的长期研究 和主动脉瓣置换术设计有严格解决瓣膜生长的测量。

项目成果

6-month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep.

• DOI: 10.1016/j.biomaterials.2015.09.016
• 发表时间: 2015-12
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Syedain Z;Reimer J;Schmidt J;Lahti M;Berry J;Bianco R;Tranquillo RT
• 通讯作者: Tranquillo RT

Pediatric tubular pulmonary heart valve from decellularized engineered tissue tubes.

• DOI: 10.1016/j.biomaterials.2015.05.009
• 发表时间: 2015-09
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Reimer, Jay M.;Syedain, Zeeshan H.;Haynie, Bee H. T.;Tranquillo, Robert T.
• 通讯作者: Tranquillo, Robert T.

Cyclic Stretch and Perfusion Bioreactor for Conditioning Large Diameter Engineered Tissue Tubes.

• DOI: 10.1007/s10439-015-1437-x
• 发表时间: 2016-05
• 期刊: Annals of biomedical engineering
• 影响因子: 3.8
• 作者: Schmidt JB;Tranquillo RT
• 通讯作者: Tranquillo RT

Effects of Intermittent and Incremental Cyclic Stretch on ERK Signaling and Collagen Production in Engineered Tissue.

• DOI: 10.1007/s12195-015-0415-6
• 发表时间: 2016-03-01
• 期刊: Cellular and molecular bioengineering
• 影响因子: 2.8
• 作者: Schmidt JB;Chen K;Tranquillo RT
• 通讯作者: Tranquillo RT

Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs.

• DOI: 10.1038/ncomms12951
• 发表时间: 2016-09-27
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Syedain, Zeeshan;Reimer, Jay;Lahti, Matthew;Berry, James;Johnson, Sandra;Tranquillo, Robert T.
• 通讯作者: Tranquillo, Robert T.