3D Bioprinting of Strong Living Scaffolds

坚固生命支架的 3D 生物打印

• 批准号: 10682568
• 负责人: Yonghui Ding
• 金额: $ 25.41万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10682568
• 关键词: 3-Dimensional; 3D Print; Address; Allografting; Anatomy; Biocompatible Materials; Biological; Biological Process; Biological Products; Biomechanics; Blood Vessels; Cartilage; Categories; Cell Survival; Cells; Chemicals; Chemistry; Clinical Research; Complex; Data; Defect; Deposition; Development; Diffusion; Disease; Elasticity; Emulsions; Encapsulated; Engineering; Family; Fibroblasts; Fibrocartilages; Formulation; Gel; Gelatin; Goals; Growth Factor; Hydrogels; In Vitro; Infiltration; Injury; Ink; Knee; Ligaments; Liquid substance; Mechanics; Medical; Meniscus structure of joint; Methods; Modality; Modeling; Modulus; Musculoskeletal; Natural regeneration; Oils; Organic solvent product; Orthopedic Surgery; Oryctolagus cuniculus; Patients; Phase; Polymers; Proliferating; Property; Quality of life; Regenerative engineering; Research; Risk; Sedimentation process; Technology; Temperature; Tendon structure; Testing; Tissues; Water; Work; adipose derived stem cell; aqueous; bioink; biomaterial compatibility; bioprinting; bioscaffold; bone; cartilage regeneration; clinical practice; cytotoxic; design; fabrication; falls; implantation; in vivo; innovation; manufacture; mechanical properties; meetings; novel; preservation; repaired; scaffold; shear stress; sound; stem cells; tissue regeneration; tissue repair; tissue support frame; transforming growth factor beta3

Project Summary The regeneration of damaged or diseased tissues that serve biomechanical functions, such as musculoskeletal tissues, has been a long-standing challenge in clinical practice and research. Regenerative engineering offers a promising alternative to auto- or allografts for tissue regeneration by combining biomaterial scaffolds, viable cells, and bioactive factors. Engineering scaffolds that provide both mechanical support and biological activities is critical for regenerating such tissues with biomechanical functions. However, currently existing scaffolds, which include either tough polymers with limited bioactivities or soft hydrogels with poor mechanical properties, fall short of meeting both mechanical and biological needs. To address this issue, we propose the development of a novel family of emulsion bioinks to enable the 3D bioprinting of strong living scaffolds with built-in mechanical robustness and desirable biological functions for tissue regeneration. The encapsulation of biologics (cells and bioactive factors) within scaffolds presents an attractive strategy to equip the scaffolds with desired biological functions. The major roadblocks to encapsulate biologics within tough polymers include their lack of bioactivity and the frequent usage of harmful chemicals, such as organic solvents and/or toxic reactants. In this study, a water-in-oil emulsion bioink is designed by dispersing an aqueous internal phase of hydrogel droplets (microgels) with encapsulated biologics in an external phase of tough polymer solution. It is hypothesized that microgels will protect the functions of encapsulated biologics from harmful chemicals by limiting their diffusion from the external to internal phases. The solidification of tough polymer around each dispersed microgel during 3D-bioprinting will mainly contribute to mechanical robustness of the final scaffold. The preliminary data demonstrates that: 1) >95% viability of fibroblast cells is achieved in an emulsion bioink; and 2) the resulting emulsion scaffolds afford both the mechanical robustness (elastic moduli 5-40 MPa) and >90% cell viability. This project will initiate with the development of cytocompatible and bioprintable cell- laden emulsion bioinks, followed by characterization of 3D-bioprinted emulsion scaffolds, and conclude with validating the functions of encapsulated bioactive factors and cells within scaffolds for meniscus regeneration as a test model. This model will include assessments of proliferation, fibrochondrogenic differentiation in vitro, and neo-menisci formation in vivo. Overall, our approach presents a new method to produce mechanically strong and biologically functional living scaffolds by integrating emulsion chemistry and 3D bioprinting technology. We anticipate that this work will have a broad and significant impact on regenerative engineering by benefiting repair or regeneration of broad-spectrum tissues with biomechanical functions.

项目概要 具有生物力学功能的受损或患病组织的再生，例如肌肉骨骼 组织，一直是临床实践和研究中长期存在的挑战。再生工程提供 通过结合生物材料支架，成为自体或同种异体移植组织再生的有前景的替代方案，可行 细胞和生物活性因子。既提供机械支撑又提供生物活性的工程支架 对于再生具有生物力学功能的组织至关重要。但目前现有的脚手架， 其中包括生物活性有限的坚韧聚合物或机械性能较差的软水凝胶， 无法满足机械和生物需求。为了解决这个问题，我们建议开发 新型乳液生物墨水家族的诞生，可实现具有内置功能的强生命支架的 3D 生物打印 机械鲁棒性和组织再生所需的生物功能。的封装 支架内的生物制剂（细胞和生物活性因子）提供了一种有吸引力的策略来装备支架 所需的生物学功能。将生物制剂封装在坚韧聚合物中的主要障碍包括 缺乏生物活性和频繁使用有害化学物质，例如有机溶剂和/或有毒反应物。 在这项研究中，通过分散水凝胶的水性内相设计了油包水乳液生物墨水 将生物制剂封装在坚韧聚合物溶液的外相中的液滴（微凝胶）。这是 假设微凝胶将通过以下方式保护封装生物制品的功能免受有害化学物质的影响 限制它们从外相到内相的扩散。每个周围都有坚韧的聚合物凝固 3D生物打印过程中分散的微凝胶将主要有助于最终支架的机械坚固性。 初步数据表明：1) 乳液生物墨水中成纤维细胞的活力达到 >95%； 2) 所得乳液支架具有机械强度（弹性模量 5-40 MPa） 和 >90% 的细胞活力。该项目将从开发细胞相容性和可生物打印的细胞开始 负载乳液生物墨水，然后是 3D 生物打印乳液支架的表征，最后得出 验证支架内封装的生物活性因子和细胞对半月板再生的功能 作为测试模型。该模型将包括体外增殖、纤维软骨分化的评估， 和体内新半月板的形成。总的来说，我们的方法提出了一种机械生产的新方法 通过整合乳液化学和 3D 生物打印，打造坚固且具有生物功能的生命支架 技术。我们预计这项工作将对再生工程产生广泛而重大的影响 通过有益于具有生物力学功能的广谱组织的修复或再生。