3D Bioprinting of Strong Living Scaffolds

坚固生命支架的 3D 生物打印

• 批准号: 10528130
• 负责人: Yonghui Ding
• 金额: $ 20.36万
• 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/10528130
• 关键词: 3-Dimensional; 3D Print; Address; Adipose tissue; 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; Emulsions; Encapsulated; Engineering; Family; Fibroblasts; Fibrocartilages; Formulation; 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; Property; Regenerative engineering; Research; Risk; Sedimentation process; Technology; Temperature; Tendon structure; Testing; The Sun; Tissues; Water; Work; aqueous; base; bioink; biomaterial compatibility; bioprinting; bioscaffold; bone; cartilage regeneration; clinical practice; cytotoxic; design; falls; implantation; in vivo; innovation; mechanical properties; meetings; novel; preservation; progenitor; repaired; scaffold; shear stress; sound; stem cells; tissue regeneration; 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.

项目摘要 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 在临床实践和研究中，组织一直是长期以来的挑战。再生工程提供 通过结合生物材料脚手架的自身或同种异体移植物的有希望的替代品 细胞和生物活性因子。提供机械支持和生物学活动的工程脚手架 对于通过生物力学功能再生的组织至关重要。但是，目前存在的脚手架， 其中包括具有有限生物活性的硬聚合物或机械性能较差的软性水凝胶， 不满足机械和生物学需求。为了解决这个问题，我们建议开发 一个新颖的乳液生物互联家族，以实现与内置的强大脚手架的3D生物打印 机械鲁棒性和组织再生的理想生物学功能。封装 脚手架内的生物制剂（细胞和生物活性因素）提出了一种有吸引力的脚手架的策略 所需的生物学功能。将生物制剂封装在韧性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内相设计的水中乳液生物互联 在硬聚合物溶液的外相中，液滴（微凝胶）带有封装的生物制剂。这是 假设微凝胶将保护包封的生物制剂的功能免受有害化学物质的影响 限制它们从外部到内部阶段的扩散。每个周围的强聚合物的凝固 在3D偶联期间分散的微凝胶将主要有助于最终支架的机械鲁棒性。 初步数据表明：1）在乳液生物互联中实现了成纤维细胞的生存能力。 2）所得的乳液支架具有机械鲁棒性（弹性模量5-40 MPa） 和> 90％的细胞活力。该项目将随着细胞相容和可生物打印细胞的发展而启动 LADEN乳液生物学，随后是3D生物的乳液支架的表征，并以 验证弯弯曲再生中封装的生物活性因子和细胞的功能 作为测试模型。该模型将包括评估增殖，体外纤维负有分化的评估， 在体内组成的新泥浆形成。总体而言，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生物打印来强大和生物学上的活生生物脚手架 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 通过使具有生物力学功能的广谱组织的修复或再生受益。