Dynamic protein-based biomaterial designs for bionic coatings

用于仿生涂层的动态蛋白质基生物材料设计

• 批准号: 2104294
• 负责人: Ying Chen
• 金额: $ 52.5万
• 依托单位: Tufts University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2104294&HistoricalAwards=false
• 关键词: Dynamic; protein; based; biomaterial; designs

NON-TECHNICAL SUMMARYThis research involves a new biomaterials strategy to protect living cells. Cells experience many types of environmental stress when they are grown in culture dishes, and can easily be killed when they are injected through a syringe. Cellular stress can also cause changes in cell functions and even trigger diseases. This project utilizes modified silk, a natural and inexpensive protein biomaterial as a barrier to isolate the cells from their surroundings and protect the cells from being stressed and damaged. Ultrathin coatings on cells will be used for cell protection under unfavorable conditions to maintain normal cell functions. The results should provide insight into new biomaterial systems and interfaces for successful cell and tissue engineering. The work will also provide education and research opportunities for a broad range of students including underrepresented minorities, post-graduate entrepreneurship students, and materials science and engineering students at Tufts and beyond via dissemination. The project will provide both virtual learning tools, modules via YouTube videos, and hands-on research opportunities to underrepresented minority students in the Boston area through collaborations with UMass Boston, Roxbury Community College and Bunker Hill Community College. These partnerships will provide a unique opportunity for underrepresented minority students to gain hands-on experience with these systems to study biomaterial designs and cell interactions.TECHNICAL SUMMARYThe goal of the project is to develop a new family of protein polymers that self-organize in a customizable layer-by-layer fashion, offer versatility in material properties (e.g., mechanics, crosslink type and degree, and provide shape-change features) and can be assembled and utilized with biological systems (e.g., as cell coatings). Nanocoating cells holds promise for protection against harsh environmental and processing conditions by isolating the cells from their surroundings within a physical barrier. The project focuses on a core strategy of building upon tough, selectively designable silk-like protein systems, with the utilization of selective chemistries to match structure-assembly-function biomaterial goals. The plan is to program these designs to modulate mechanics, dynamic shape changes and cell surface assembly, to establish new systems for versatile control of self-assembly that can be programmed for robust mechanical properties in the context of sensitive biological systems such as cells, enzymes and other biological entities. The strategies presented here provide potential benefits for surface engineering of cells, 3D printing, and preservation. Nanocoated cells would find use in clinical and biotechnology applications during in vitro and in vivo manipulation, where cells are exposed to a variety of stresses including proteolytic enzymes, immune attack, or hydrodynamic forces in bioreactors, in the host, or during injection-based delivery or 3D bioprinting. The work will also provide a focus for training underrepresented minority groups in techniques connecting material science and cell/tissue engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

非技术总结这项研究涉及一种保护活细胞的新生物材料策略。细胞在培养皿中生长时会经历许多类型的环境压力，通过注射器注射很容易被杀死。细胞应激也会导致细胞功能的改变，甚至引发疾病。该项目利用改性丝素，一种天然且廉价的蛋白质生物材料作为屏障，将细胞与周围环境隔离，保护细胞免受压力和损害。细胞上的超薄涂层将用于在不利条件下保护细胞，以维持正常的细胞功能。这些结果应该为成功的细胞和组织工程提供对新的生物材料系统和接口的洞察。这项工作还将通过传播为广泛的学生提供教育和研究机会，包括代表性不足的少数族裔、研究生创业学生以及塔夫茨大学和其他地方的材料科学和工程专业的学生。该项目将通过与波士顿大学波士顿分校、罗克斯伯里社区学院和邦克山社区学院的合作，为波士顿地区未被充分代表的少数族裔学生提供虚拟学习工具、YouTube视频模块和动手研究机会。这些合作伙伴关系将为未被充分代表的少数族裔学生提供一个独特的机会，让他们亲身体验这些系统，学习生物材料设计和细胞相互作用。技术总结该项目的目标是开发一种新的蛋白质聚合物家族，该家族以可定制的逐层方式自组织，提供材料特性的多样性(例如，力学、交联度和程度，并提供形状变化特征)，并且可以与生物系统一起组装和利用(例如，作为细胞涂层)。纳米涂层细胞通过在物理屏障内将细胞与周围环境隔离，有望保护细胞免受恶劣环境和工艺条件的影响。该项目的重点是一个核心战略，即建立在坚韧的、可选择性设计的类丝蛋白系统的基础上，利用选择性化学来匹配结构-组装-功能生物材料的目标。我们的计划是对这些设计进行编程，以调节力学、动态形状变化和细胞表面组装，建立新的多功能自组装控制系统，这些系统可以在细胞、酶和其他生物实体等敏感生物系统的背景下进行编程，以获得强大的机械性能。本文提出的策略为细胞表面工程、3D打印和保存提供了潜在的好处。在体外和体内操作过程中，纳米涂层细胞将被用于临床和生物技术应用，在这些操作中，细胞暴露在各种压力下，包括生物反应器、宿主中的蛋白质水解酶、免疫攻击或流体动力，或者在注射递送或3D生物打印期间。这项工作还将提供一个重点，在连接材料科学和细胞/组织工程的技术方面培训未被充分代表的少数群体。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Feedback-controlled dynamics of neuronal cells on directional surfaces

• DOI: 10.1016/j.bpj.2022.01.020
• 发表时间: 2022-03-01
• 期刊: BIOPHYSICAL JOURNAL
• 影响因子: 3.4
• 作者: Descoteaux, Marc;Sunnerberg, Jacob P.;Staii, Cristian
• 通讯作者: Staii, Cristian

Cytoprotection of Human Progenitor and Stem Cells through Encapsulation in Alginate Templated, Dual Crosslinked Silk and Silk-Gelatin Composite Hydrogel Microbeads.

通过封装在藻酸盐模板上，双重交联的丝绸和丝绸明星蛋白复合水凝胶微粒中，人类祖细胞和干细胞的细胞保护作用。

• DOI: 10.1002/adhm.202200293
• 发表时间: 2022-09
• 期刊: ADVANCED HEALTHCARE MATERIALS
• 影响因子: 10
• 作者: Hasturk, Onur;Smiley, Jordan A.;Arnett, Miles;Sahoo, Jugal Kishore;Staii, Cristian;Kaplan, David L.
• 通讯作者: Kaplan, David L.

Synthesis and Characterization of Silk Ionomers for Layer-by-Layer Electrostatic Deposition on Individual Mammalian Cells.

• DOI: 10.1021/acs.biomac.0c00523
• 发表时间: 2020-07-13
• 期刊: Biomacromolecules
• 影响因子: 6.2
• 作者: Hasturk O;Sahoo JK;Kaplan DL
• 通讯作者: Kaplan DL