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 高度组织化和血管化的三维（3D）组织构建体的体外开发具有重要意义。 组织工程的重要性，因为天然肌肉组织表现出高度组织化的3D复合体， 由细胞外基质（ECM）、不同细胞类型以及化学和物理性质组成的结构 信号提示生物打印已经成为开发高度复杂的3D结构的新技术; 然而，仍然存在许多挑战，例如需要精确定位/切换 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，并创建图案 类似于体内环境的物理特性。为了应对这些挑战，我们计划开发 - 嵌入式多材料生物打印（EMB）技术，其采用自修复支持水凝胶， 可编程微流体装置。多材料生物打印（MB）系统可以通过以下方式开发： 直接写入3D生物打印系统与高精度可编程微流体打印头的集成， 其可以容易且快速地在不同的材料、试剂和细胞之间切换。多轴挤压 系统能够产生用于肌肉束和可灌注血管网络的多尺度微纤维， 模仿其空间组织的自然对应物的机械性能和结构。虽然 难以精确控制材料在Z方向上的位置以产生独立的水凝胶结构， 我们将通过结合嵌入式3D生物打印技术， 通过使用自我修复的支撑水凝胶。此外，支持水凝胶将能够实现快速 在X-Y-Z方向上沉积所需的预聚物溶液，而无需额外的凝胶化处理。通过 将这种嵌入式打印策略与包含MB技术的微流体装置相结合， 我们打印具有生物相关架构的多组分/多细胞组织构建体， 这些特征目前很难或不可能生物打印。此外，使用载有细胞的生物墨水， 模拟肌肉组织的机械和生物特性，可以作为一个平台， 肌肉前体的分化和成熟，以及改善的收缩活性。可以设想 该项目的成功开发将对肌肉愈合能力产生重大影响， 创伤以及推进肌肉组织工程领域。此外，该方法可以容易地 应用于再生医学的其他领域，以产生新的器官。