3D Freeform Ice Printing to Create Tissues with Biomimetic Vasculature

3D 自由形式冰打印可创建具有仿生脉管系统的组织

• 批准号: 10584519
• 负责人: Burak O. Ozdoganlar
• 金额: $ 13.95万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584519
• 关键词: 3-Dimensional; 3D Print; Address; Area; Artificial tissue; Biocompatible Materials; Biological Assay; Biomimetics; Bladder; Blood Vessels; Blood flow; Cartilage; Cell Culture Techniques; Cell Death; Cell Survival; Cells; Cellular Assay; Collaborations; Collagen; Complex; Data; Dermal; Development; Diameter; Diffusion; Electron Microscopy; Endothelial Cells; Endothelium; Engineering; Excision; Fibroblasts; Freeze Drying; Future; Geometry; Goals; Heart; Heart Valves; Human; Ice; Image; Immunofluorescence Microscopy; Life; Liquid substance; Liver; Mechanics; Microfabrication; Natural regeneration; Nutrient; Organ; Organ Transplantation; Patients; Pharmacologic Substance; Physiological; Porosity; Printing; Process; Property; Publications; Publishing; Recording of previous events; Regenerative Medicine; Reproducibility; Research; Research Infrastructure; Scientist; Shapes; Skin; Skin Tissue; Spatial Distribution; Structure; Students; System; Techniques; Testing; Thick; Time; Tissue Engineering; Tissue constructs; Tissues; Transplantation; Vascularization; Water; Waxes; Work; acetyl-LDL; bone; clinically relevant; doctoral student; experience; experimental study; fabrication; human tissue; implantation; innovation; knowledge of results; manufacture; microsystems; mimetics; novel; organ on a chip; oxygen transport; pathogen; response; scaffold; sublimation; tissue support frame; transplantation medicine; uptake; wasting

PROJECT SUMMARY For more than three decades, scientists have aspired to create engineered tissues that mimic the remarkable physiological and functional properties of natural tissues. Such tissues and organs can be used not only for transplantation to save lives but also for ex vivo tissue-on-a-chip approaches to test pharmaceuticals the response to pathogens. However, we still lack the ability to create tissues with three-dimensional tissue-mimetic vasculature. Without 3D, smooth branched, and multi-scale vascular networks, which facilitate nutrient/oxygen transport, engineered full-thickness tissues will not be fully functional due to cell death limited by diffusion. As such, biomimetic vasculature networks are very important for viable and clinically relevant tissue constructs. We propose an innovative approach to address the challenge of fabricating tissue constructs with biomimetic vasculature. Our approach involves 3D freeform ice printing of sacrificial vasculature templates and uses them to fabricate scaffolds for creating biomimetic vascularized tissue constructs. Our novel 3D freeform (as opposed to layer-by-layer) ice printing process uniquely enables fabricating ice templates that mimic the geometry of the actual vasculature, including complex shapes, circular cross-sections, and varying diameters and branched structures with smooth transitions. Our fundamental hypothesis is that our 3D ice printing technique enables the creation of tissue scaffolds with biomimetic 3D vasculature networks. In this R21 project, we aim to develop our 3D ice printing-based vascularized tissue fabrication platform and to demonstrate its feasibility by creating human-skin tissue-on-a-chip systems with 3D biomimetic vasculature that also in the future can be used for tissue implantation. Our preliminary results show our general ability to print multi-scale ice structures, fabricate porous scaffolds with vasculature conduits, and grow endothelial and fibroblasts cells on porous dissolvable scaffolds. The proposed studies aim to show the feasibility of our approach towards creating vascularized tissues. Our approach, based on our preliminary data and published experience, will involve two Specific Aims: Aim 1 will focus on the development of our 3D ice printing technique to reproducibly create defined biomimetic vasculature within porous tissue scaffolds. Aim 2 will demonstrate our approach for creating 3D vascularized tissue-on-a-chip constructs using the fabricated scaffolds and multiple cell systems. Our interdisciplinary project team combines complementary expertise and research infrastructure that directly addresses the proposed project. The PIs have a decade-long history of strong collaboration, including co-advised PhD students and multiple co-authored publications. We expect the results of this work will bring the ability to create tissue scaffolds with 3D biomimetic vasculature toward creating many different vascularized tissues and organs in the future. This will have a profound effect on the tissue engineering field, impacting tissue- on-a-chip, patient-specific organ transplantation, and regenerative medicine areas.

项目摘要 三十多年来，科学家一直渴望创建模仿非凡的工程组织 天然组织的生理和功能特性。这样的组织和器官不仅可以用于 移植以挽救生命，但也用于实体组织，以测试药物 对病原体的反应。但是，我们仍然缺乏创建具有三维组织模拟组织的组织的能力 脉管系统。没有3D，平滑的分支和多尺度的血管网络，可促进营养/氧气 由于细胞死亡受到扩散的限制，运输，设计的全厚组织将无法完全发挥功能。作为 这样的仿生脉管网络对于可行和临床相关的组织结构非常重要。 我们提出了一种创新的方法，以应对用仿生型制造组织结构的挑战 脉管系统。我们的方法涉及牺牲脉管系统模板的3D自由形式冰印并使用它们 制造脚手架来产生仿生的血管化组织构建体。我们的小说3D Freeform（而不是 逐层）冰印过程独特地使制造模仿几何形状的冰模板 实际的脉管系统，包括复杂形状，圆形横截面以及直径变化和分支 具有平稳过渡的结构。我们的基本假设是我们的3D冰印技术使得 用仿生3D脉管网络创建组织支架。在这个R21项目中，我们旨在发展我们的 基于3D冰印的血管组织制造平台，并通过创建创建其可行性 带有3D仿生脉管系统的人体皮组织，将来也可以用于 组织植入。我们的初步结果表明我们打印多尺度冰结构的一般能力，制造 带有脉管导管的多孔脚手架，生长内皮和成纤维细胞在多孔溶解上 脚手架。拟议的研究旨在展示我们创建血管化的方法的可行性 组织。根据我们的初步数据和已发表的经验，我们的方法将涉及两个具体的目标： AIM 1将专注于我们3D冰印技术的开发，以重复创建定义的仿生型 多孔组织支架内的脉管系统。 AIM 2将展示我们创建3D血管化的方法 使用制造的脚手架和多个细胞系统的芯片组织构造。 我们的跨学科项目团队结合了补充专业知识和研究基础设施， 直接解决拟议项目。 PI有十年的牢固合作历史，包括 共同审议的博士生和多个共同的出版物。我们希望这项工作的结果将带来 能够创建具有3D仿生脉管系统的组织支架，以创建许多不同的血管化 将来的组织和器官。这将对组织工程领域产生深远的影响，从而影响组织 片上，特定于患者的器官移植和再生医学领域。