Programmable multimaterial bioprinting of 3D vascularized tissue constructs

3D 血管化组织结构的可编程多材料生物打印

• 批准号: 9788446
• 负责人: Su Ryon Shin
• 金额: $ 21.98万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788446
• 关键词: 3-Dimensional; Address; Affect; American; Architecture; Area; Automobile Driving; Biocompatible Materials; Biological; Blood Vessels; Cell Differentiation process; Cell Maturation; Cell Survival; Cells; Characteristics; Chemicals; Complex; Cues; Dependence; Deposition; Development; Diffusion; Dimensions; Disease; Elasticity; Endothelial Cells; Engineering; Environment; Exhibits; Extracellular Matrix; Gelatin; Human; Hydrogels; In Vitro; Mechanics; Microfabrication; Microfluidic Microchips; Microfluidics; Modeling; Muscle; Muscle Fibers; Myoblasts; Natural regeneration; Nutrient; Operative Surgical Procedures; Organ; Organ failure; Oxygen; Patients; Pattern; Polymers; Positioning Attribute; Printing; Problem Solving; Process; Property; Prunella vulgaris; Reagent; Recombinants; Regenerative Medicine; Risk; Signal Transduction; Skeletal Muscle; Structure; System; Technology; Time; Tissue Engineering; Tissue Transplantation; Tissues; Transplanted tissue; Trauma; Traumatic injury; Tropoelastin; Ursidae Family; Writing; angiogenesis; base; bioprinting; blood perfusion; cell type; clinically relevant; cost; healing; improved; in vivo; injured; mechanical properties; new technology; novel; physical property; programs; technology development; three dimensional structure; tumor ablation

Project Summary In vitro development of highly organized and vascularized three-dimensional (3D) tissue constructs is of great importance in tissue engineering, since native muscle tissues exhibit highly organized 3D complex architectures composed of an extracellular matrix (ECM), different cell types, and chemical and physical signaling cues. Bioprinting has emerged as a new technology to develop highly complex, 3D structures; however, there are many remaining challenges, such as the necessity for precise positioning/switching of different cell-types and materials to create multi-cellular 3D structures with various sizes, and creating patterns that resemble the physical properties of in vivo environments. To address these challenges, we plan to develop an embedded multi-material bioprinting (EMB) technology that employs a self-healing supporting hydrogel and a programmable microfluidic device. The multi-material bioprinting (MB) system can be developed by integration of a direct-write 3D bioprinting system with a high precision, programmable microfluidic printhead, which can easily and quickly switch between different materials, reagents and cells. The multi-axial extrusion systems are able to create multi-scale microfibers for muscle bundles and perfusable blood vessel networks to mimic the mechanical properties and architecture of their spatially organized natural counterparts. While it is difficult to precisely control the materials’ position in Z directions to create freestanding hydrogel architectures, we will improve the high print fidelity of the MB system by combining an embedded 3D bioprinting technology by using a self-healing supporting hydrogel. In addition, the supporting hydrogel will be able to achieve fast deposition of the desired pre-polymer solution in X-Y-Z directions without additional gelation processing. By combining this embedded printing strategy with the microfluidic device incorporated MB technology, it will allow us to print multi-component/multi-cellular tissue constructs with biologically relevant architectures and characteristics that are difficult or impossible to bioprint at present. Furthermore, the use of a cell-laden bioink, which mimics the mechanical and biological properties of muscle tissue, can act as a platform to promote differentiation and maturation of muscle precursors, as well as improved contractile activity. It is envisioned that the successful development of this project will have a significant impact on the ability to heal muscle trauma as well as to advance the field of muscle tissue engineering. Furthermore, this process can be readily applied to other areas of regenerative medicine to generate new organs.

项目摘要 高度组织和血管化的三维（3D）组织构建体的体外发展非常好 在组织工程中的重要性，因为天然肌肉时间暴露了高度有条理的3D复合物 由细胞外基质（ECM），不同的细胞类型以及化学和物理的体系结构 信号提示。生物印刷已成为一种开发高度复杂的3D结构的新技术。 但是，还有许多剩余的挑战，例如精确定位/切换的必要挑战 不同的细胞类型和材料，以创建具有各种尺寸的多细胞3D结构，并创建模式 这类似于体内环境的物理特性。为了应对这些挑战，我们计划发展 一种嵌入的多物质生物打印（EMB）技术，该技术采用了支持水凝胶的自我修复和 可编程的微流体设备。多物质生物打印（MB）系统可以由 集成具有高精度，可编程的微流体Printhead的直接3D生物打印系统 可以轻松，快速地在不同的材料，试剂和细胞之间切换。多轴扩展 系统能够为肌肉束和灌注血管网络创建多尺度的超纤维 模仿其空间组织的自然对应物的机械性能和结构。虽然是 难以精确控制材料在z方向上的位置，以创建独立的水凝胶体系结构， 我们将通过组合嵌入式3D生物打印技术来提高MB系统的高印刷保真度 通过使用支撑水凝胶的自我修复。此外，支撑水凝胶将能够快速实现 所需的预聚合物溶液在X-Y-Z方向上的沉积，而无需额外的凝胶化处理。经过 将这种嵌入式打印策略与微流体设备合并的MB技术相结合，它将允许 我们要使用具有生物学相关架构的多组分/多细胞组织结构 目前难以或不可能生物的特征。此外，使用含有细胞的生物学 模仿肌肉组织的机械和生物学特性，可以作为促进的平台 肌肉前体的分化和成熟，以及改善的收缩活性。它是设想的 该项目的成功发展将对治愈肌肉的能力产生重大影响 创伤以及促进肌肉组织工程领域。此外，这个过程很容易 应用于再生医学的其他领域来产生新的器官。