High-throughput Spheroid Bioprinting Technology for Scalable Fabrication of Tissues

用于可扩展组织制造的高通量球体生物打印技术

• 批准号: 10744937
• 负责人: Ibrahim Ozbolat
• 金额: $ 52.82万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10744937
• 关键词: 3-Dimensional; Air; Alginates; Anatomy; Bathing; Benchmarking; Biocompatible Materials; Bone Tissue; Cell Density; Cell Survival; Cells; Collaborations; Complex; Craniofacial Abnormalities; Data; Defect; Deposition; Development; Device or Instrument Development; Disease model; Drug Screening; Effectiveness; Encapsulated; Exhibits; Extracellular Matrix; Gel; Goals; Human; Hydrogels; Individual; Industry; Ink; Knowledge; Measurable; Medical; Modeling; Nude Rats; Operative Surgical Procedures; Organ; Organoids; Pattern; Physiological; Polymers; Positioning Attribute; Process; Property; Rattus; Regenerative Medicine; Science; Shapes; Site; Speed; Structure; Structure of parenchyma of lung; Surface; Techniques; Technology; Testing; Tissue Engineering; Tissue Transplantation; Tissues; Translations; Work; bioprinting; bone; cell injury; craniofacial; craniofacial repair; craniomaxillofacial; density; design; drug testing; experience; fabrication; high throughput technology; instrument; manufacturing technology; new technology; novel; osteogenic; process repeatability; repaired; scaffold; self assembly; technology development; tool

ROJECT SUMMARY/ABSTRACT The ability to bioprint cellular aggregates, such as spheroids, in a high-throughput manner into desired patterns or cellular microenvironments is crucial to facilitate fabrication of scalable constructs with cell densities similar to that of native tissues and organs. Despite the progress in spheroid bioprinting technologies, the major shortcomings associated with them, such as poor positioning of spheroids, significant loss of viability and structural integrity, poor repeatability of the process when using non-uniform size spheroids, inability to form complex 3D shapes, and most importantly, the lack of scalability, limit their translation. In this project, we propose a highly unique technology, henceforth referred as “high-throughput spheroid (HTS) bioprinting,” that enables simultaneous bioprinting of several spheroids with an order of magnitude size range and minimal cellular damage, at a high positional precision and an unprecedented speed. The proposed technology is highly versatile and enables the bioprinting of complex structures either (1) onto the surface of gel substrates (i.e., hydrogels) in a scaffold-based manner or (2) within support baths (i.e., sacrificial microgels) in a scaffold-free manner for scalable fabrication of tissues. In Specific Aim 1, we propose to develop HTS bioprinting, which has the capability of depositing several spheroids simultaneously on 3D gel substrates, thus bioprinting a complete layer of the 3D tissue at once in a rapid fashion (i.e., 100 spheroids can be bioprinted in <20 sec). We will couple HTS bioprinting with extrusion-based bioprinting of gel substrates and explore the spheroid-gel interactions, across a wide range of hydrogels, during the bioprinting process. To exemplify the technology, we will demonstrate bioprinting intraoperatively via depositing osteogenically-committed bone spheroids for the repair of craniomaxillofacial bone defects in a rat model. In Specific Aim 2, we will reconfigure the HTS bioprinting technology for freeform positioning of spheroids within sacrificial support baths. Here, we will bioprint spheroids sequentially (one after the other) in a rapid manner and pattern them according to the target design. We will explore the gel-spheroid- bioprinting process interactions, where the effectiveness of the technology will be tested for multiple support baths, including alginate microgels to be fabricated using the air-jet assisted coaxial flow technique along with a commercially available benchmark. We will exemplify the utilization of the technology for fabrication of anatomically-relevant complex-shaped human bronchopulmonary segments. In this regard, we have formed a complementary collaboration that merges essential domain knowledge in bioprinting, bioprinting process and instrument development, biomaterials, craniofacial surgery, and bone and lung tissue engineering with the depth necessary to propel the proposed work towards meaningful advances that would otherwise not be possible. Successful completion of the proposed work is anticipated to give rise to an advanced bioprinting technology for HTS bioprinting and thereby provide a novel tool for fabrication of scalable tissues and organs.

项目概要/摘要 能够以高通量方式将细胞聚集体（例如球体）生物打印成所需的图案 或细胞微环境对于促进细胞密度类似于的可扩展构建体的制造至关重要 尽管球体生物打印技术取得了进展，但主要的技术仍然存在。 与它们相关的缺点，例如球体定位不良、活力显着丧失和 结构完整性，使用尺寸不均匀的球体时过程的重复性差，无法形成 复杂的 3D 形状，最重要的是，缺乏可扩展性，限制了它们的翻译。在这个项目中，我们建议。 一种独特的高科技，下文称为“高通量球体（HTS）生物打印”，能够实现 同时生物打印几个具有数量级尺寸范围和最小细胞的球体 所提出的技术具有高度的通用性。 并能够将复杂结构生物打印 (1) 到凝胶基底（即水凝胶）的表面上 基于支架的方式或（2）在支持浴（即牺牲微凝胶）内以无支架的方式进行 在具体目标 1 中，我们建议开发具有这种能力的 HTS 生物打印技术。 在 3D 凝胶基底上同时沉积多个球体，从而生物打印完整的 3D 层 一次快速组织（即，可以在 <20 秒内生物打印 100 个球体）。我们将结合 HTS 生物打印。 通过基于挤出的凝胶基质生物打印，并在广泛的范围内探索球体-凝胶相互作用 水凝胶，在生物打印过程中为了举例说明该技术，我们将演示生物打印。 术中通过沉积成骨定向骨球体来修复颅颌面 在特定目标 2 中，我们将重新配置自由形式的 HTS 生物打印技术。 将球体放置在牺牲支撑浴中 在这里，我们将依次对球体进行生物打印（一个后一个）。 另一个）快速地根据目标设计对它们进行图案化，我们将探索凝胶球体。 生物打印过程相互作用，将测试技术的有效性以获得多种支持 浴，包括使用喷气辅助同轴流技术以及 我们将举例说明该技术在制造中的应用。 解剖学上相关的复杂形状的人类支气管肺段在这方面，我们已经形成了一个。 互补的合作，融合了生物打印、生物打印过程和 仪器开发、生物材料、颅面外科、骨肺组织工程等具有深度 推动拟议的工作取得有意义的进展是必要的，否则这是不可能的。 成功完成拟议工作预计将产生先进的生物打印技术 HTS 生物打印从而为制造可扩展的组织和器官提供了一种新的工具。