Directed Self Assembly of Complex Branching Micro-Tissues

复杂分支微组织的定向自组装

• 批准号: 7914348
• 负责人: Lambert Freund
• 金额: $ 33.66万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7914348
• 关键词: Address; Adhesions; Adhesives; Age; Anastomosis - action; Area; Automobile Driving; Behavior; Binding; Biological Models; Cadherins; Caliber; Canis familiaris; Cell Adhesion; Cell Adhesion Molecules; Cell Line; Cell Separation; Cell physiology; Cell surface; Cells; Cellular Structures; Cellular biology; Complex; Coupled; Cytoskeletal Proteins; Data; Devices; Diffusion; Endothelial Cells; Excision; Fibroblasts; Figs - dietary; Foundations; Goals; Hepatocyte; Hour; Human; Hydrogels; Image; Integrins; Intermediate Filaments; Legal patent; Length; Manuscripts; Measures; Mediating; Microfilaments; Modeling; Molds; Molecular; Mono-S; Myosin Type II; Organ; Organ Transplantation; Pharmaceutical Preparations; Process; Production; Property; Proteins; Radial; Regenerative Medicine; Relative (related person); Retinal Cone; Role; Sepharose; Shapes; Smooth Muscle Myocytes; Sorting - Cell Movement; Stress; Structure; Surface; Suspension substance; Suspensions; System; Technology; Testing; Time; Tissue Engineering; Tissue Model; Tissues; Transplantation; Umbilical cord structure; Variant; Vascularization; Veins; Width; base; bone; cell type; design; drug development; insight; mathematical model; new technology; novel; public health relevance; pulmonary artery endothelial cell; repaired; retinal rods; scaffold; self assembly

We've developed a new technology based on micro-molded nonadhesive agarose to guide the self assembly of 3D micro-tissues. Mono-disperse cells are pipetted into the micro-mold, they settle into the molded features, are unable to bind to the nonadhesive agarose and so spontaneously self assembly 3D micro-tissues. By making complex features in the micro-molds, we've shown for the first time that cells will self assembly complex structures such as rods, toroids and honeycombs. Little is understood about the rules that govern this directed cellular self-assembly process, especially for complex branching structures and so the overarching goal of this proposal is to define and quantify these rules. Our hypothesis is that the rules of selfassembly differ between specific cell types and that in addition to surface adhesive forces, cytoskeletal mediated tension/contraction contribute to cell specific differences and significantly influence the directed self assembly of complex micro-tissues. To test this hypothesis and define the rules of directed self assembly, we propose to use five cell lines and their mixtures, normal human fibroblasts (NHF), a hepatocyte cell line (H35), smooth muscle cells (SMC) and two endothelial cell lines; human umbilical cord vein endothelial cells (HUVEC) and calf pulmonary artery endothelial cells (CPAE) to test the following specific aims: Aim 1. To determine cell type differences in directed self assembly and their ability to generate complex shapes. Aim 2. To quantify the respective roles of cytoskeletal mediated contraction and cell surface adhesion proteins on directed self-assembly. Modified

我们开发了一种基于微成型非粘性琼脂糖的新技术，用于指导3D微组织的自组装。将单分散的细胞移液到微模具中，它们沉降到模制特征中，不能结合到非粘附性琼脂糖上，因此自发地自组装3D微组织。通过在微型模具中制造复杂的特征，我们首次展示了细胞将自我组装复杂的结构，如杆，环和蜂窝。关于控制这种定向细胞自组装过程的规则，特别是对于复杂的分支结构，人们知之甚少，因此本提案的首要目标是定义和量化这些规则。我们的假设是，自组装的规则在特定的细胞类型之间不同，除了表面粘附力，细胞骨架介导的张力/收缩有助于细胞特异性差异，并显着影响复杂微组织的定向自组装。为了验证这一假设并定义定向自组装的规则，我们建议使用五种细胞系及其混合物，正常人成纤维细胞（NHF），肝细胞系（H35），平滑肌细胞（SMC）和两种内皮细胞系;人脐带静脉内皮细胞（HUVEC）和小牛肺动脉内皮细胞（CPAE）来测试以下具体目标：目的1。确定定向自组装的细胞类型差异及其生成复杂形状的能力。目标二。量化细胞骨架介导的收缩和细胞表面粘附蛋白对定向自组装的各自作用。 改性

项目成果

Advances in the formation, use and understanding of multi-cellular spheroids.

• DOI: 10.1517/14712598.2012.707181
• 发表时间: 2012-10
• 期刊: Expert opinion on biological therapy
• 影响因子: 4.6
• 作者: Achilli TM;Meyer J;Morgan JR
• 通讯作者: Morgan JR

Directed self-assembly of large scaffold-free multi-cellular honeycomb structures.

• DOI: 10.1088/1758-5082/3/3/034110
• 发表时间: 2011-09
• 期刊: Biofabrication
• 影响因子: 9
• 作者: Tejavibulya N;Youssef J;Bao B;Ferruccio TM;Morgan JR
• 通讯作者: Morgan JR

Mechanotransduction is enhanced by the synergistic action of heterotypic cell interactions and TGF-β1.

异型细胞相互作用和 TGF-β1 的协同作用增强了机械转导。

• DOI: 10.1096/fj.11-199414
• 发表时间: 2012
• 期刊: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 作者: Youssef,Jacquelyn;Chen,Peng;Shenoy,VivekB;Morgan,JeffreyR
• 通讯作者: Morgan,JeffreyR

The Influence of Dimensionality on the Rate of Diffusive Escape From an Energy Well.

维数对能量井扩散逃逸速率的影响。

• DOI: 10.1115/1.4005895
• 发表时间: 2012
• 期刊: Journal of applied mechanics
• 作者: Freund,LB

Micro-mold design controls the 3D morphological evolution of self-assembling multicellular microtissues.

微模具设计控制自组装多细胞微组织的 3D 形态演化。

• DOI: 10.1089/ten.tea.2013.0297
• 发表时间: 2014
• 期刊: Tissue engineering. Part A
• 作者: Svoronos,AlexanderA;Tejavibulya,Nalin;Schell,JacquelynY;Shenoy,VivekB;Morgan,JeffreyR
• 通讯作者: Morgan,JeffreyR