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.

项目概要 三十多年来，科学家们一直渴望创造出模仿非凡的工程组织 自然组织的生理和功能特性。这些组织和器官不仅可以用于 移植可以拯救生命，也可以用于离体组织芯片方法来测试药物 对病原体的反应。然而，我们仍然缺乏用三维组织模拟来制造组织的能力 脉管系统。没有 3D、光滑分支和多尺度的血管网络，有利于营养/氧气 在运输过程中，由于细胞死亡受到扩散限制，工程化的全层组织将无法完全发挥功能。作为 因此，仿生脉管系统网络对于可行且临床相关的组织构建非常重要。 我们提出了一种创新方法来解决仿生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 自由形式冰打印并使用它们 制造用于创建仿生血管化组织结构的支架。我们新颖的 3D 自由形式（与 逐层）冰印刷工艺独特地能够制造模仿冰的几何形状的冰模板 实际的脉管系统，包括复杂的形状、圆形横截面、不同的直径和分支 具有平滑过渡的结构。我们的基本假设是，我们的 3D 冰打印技术能够实现 使用仿生 3D 脉管系统网络创建组织支架。在这个 R21 项目中，我们的目标是开发我们的 基于3D冰打印的血管化组织制造平台，并通过创建来证明其可行性 具有 3D 仿生脉管系统的人体皮肤组织芯片系统，未来也可用于 组织植入。我们的初步结果表明我们具有打印多尺度冰结构、制造 具有血管导管的多孔支架，并在多孔可溶性上生长内皮细胞和成纤维细胞 脚手架。拟议的研究旨在展示我们创建血管化方法的可行性 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目标： 目标 1 将重点开发我们的 3D 冰打印技术，以可重复地创建定义的仿生材料 多孔组织支架内的脉管系统。目标 2 将展示我们创建 3D 血管化的方法 使用制造的支架和多细胞系统构建芯片上的组织。 我们的跨学科项目团队结合了互补的专业知识和研究基础设施， 直接解决拟议的项目。 PI 有着长达十年的强有力合作历史，包括 共同指导博士生和多篇共同撰写的出版物。我们期望这项工作的成果将带来 能够创建具有 3D 仿生血管系统的组织支架，以创建许多不同的血管化 未来的组织和器官。这将对组织工程领域产生深远的影响，影响组织- 芯片上、患者特异性器官移植和再生医学领域。