Cryobioprinting for Shelf-Ready Tissue Fabrication and Storage

用于货架组织制造和储存的冷冻生物打印

• 批准号: 10927669
• 负责人: Yu Shrike Zhang
• 金额: $ 49.93万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2024-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10927669
• 关键词: 3-Dimensional; Address; Adopted; Biological Assay; Cells; Clinical; Collagen; Cryopreservation; Cryopreserved Tissue; Cryoprotective Agents; Engineering; Formulation; Freezing; Future; Gelatin; Goals; Height; Hyaluronic Acid; Hydrogels; Implant; In Situ; In Vitro; Industrialization; Laboratories; Methodology; Methods; Organoids; Outcome; Performance; Printing; Process; Production; Property; Rodent; Sampling; Scheme; Shapes; Site; Structure; Techniques; Technology; Temperature; Testing; Tissue Engineering; Tissue Model; Tissue constructs; Tissues; Trachea; Transplantation Surgery; biofabrication; bioink; bioprinting; cell dimension; chorioallantoic membrane; clinical application; clinical translation; cold temperature; crosslink; cryogenics; design; experimental study; fabrication; in vivo; next generation; preservation; translational potential

Abstract Three-dimensional (3D) bioprinting has paved a new avenue for fabricating intricate cell-laden tissue constructs. So far, bioprinting has been adopted in myriad applications such as tissue engineering, tissue model engineering, and organoid production, among others. There are, however, challenges regarding the fabrication and storage of shelf-ready 3D-bioprinted tissue constructs. Due to the intrinsic complexities involved in most bioprinting processes, including the broadly adopted extrusion bioprinting, using this method as an on- site fabrication technique can be cumbersome, or sometimes impractical under a number of scenarios. Furthermore, the lack of a functional approach for long-term storage of cell-laden tissue constructs precludes the shelf-availability of pre-made bioprinted products. Here, we propose to develop a unique cryobioprinting strategy for simultaneously fabricating and storing cell-laden volumetric tissue constructs through seamlessly combining cell-laden extrusion bioprinting and cryopreservation. The cryobioprinting performances will be investigated by designing, fabricating, and storing cell-laden constructs made of cryoprotective bioinks using a freezing plate with precisely controllable temperature. The in situ freezing process is further anticipated to promote the printability of cell-laden hydrogel bioinks to achieve freeform structures otherwise oftentimes inconvenient with direct extrusion bioprinting. We believe that our cryobioprinting will emerge as a single-step method for concurrent tissue biofabrication and storage.

摘要 三维（3D）生物打印为制造复杂的细胞负载组织铺平了新的道路 结构。到目前为止，生物打印已被用于无数应用，如组织工程，组织工程，组织工程和组织工程。 模型工程和类器官生产等等。然而，在这方面存在着挑战。 制造和储存现成的3D生物打印组织构建体。由于涉及的内在复杂性 在大多数生物打印过程中，包括广泛采用的挤出生物打印，使用这种方法作为一种非生物打印方法， 现场制造技术在许多情况下可能是麻烦或有时是不切实际的。 此外，缺乏长期储存载有细胞的组织构建体的功能性方法， 预制生物打印产品的货架可用性。在这里，我们建议开发一种独特的低温生物打印技术， 同时制造和储存载有细胞的体积组织构建体的策略 结合载有细胞的挤压生物打印和低温保存。低温生物打印的表现将是 通过设计、制造和储存由冷冻保护生物墨水制成的载有细胞的结构， 温度可精确控制的冷冻板。进一步预计，原位冷冻过程将 促进载有细胞的水凝胶生物墨水的可印刷性以实现自由形式的结构 不便于直接挤出生物打印。我们相信，我们的低温生物打印技术将成为一个单一的步骤， 同时进行组织生物制造和储存的方法。