Dynamic protein-based biomaterial designs for bionic coatings

本研究涉及一种新的生物材料策略来保护活细胞。当细胞在培养皿中生长时，它们会经历多种类型的环境压力，并且当它们通过注射器注射时很容易被杀死。细胞压力也会引起细胞功能的变化，甚至引发疾病。该项目利用改良的丝，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开来，保护细胞免受压力和破坏。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。该结果将为成功的细胞和组织工程提供新的生物材料系统和界面。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民族、研究生创业专业学生、塔夫茨大学及其他院校的材料科学与工程专业学生。该项目将通过与马萨诸塞大学波士顿分校、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民族学生提供虚拟学习工具、YouTube视频模块和实践研究机会。这些伙伴关系将为代表性不足的少数民族学生提供一个独特的机会，以获得这些系统的实践经验，研究生物材料设计和细胞相互作用。技术概述：该项目的目标是开发一种新的蛋白质聚合物家族，该家族以可定制的一层一层的方式自组织，提供材料特性的多功能性（例如，力学，交联类型和程度，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）。纳米涂层电池通过将细胞与周围环境隔离在物理屏障内，有望保护细胞免受恶劣环境和加工条件的影响。该项目侧重于建立坚韧的、可选择性设计的丝状蛋白质系统的核心策略，利用选择性化学来匹配结构-组装-功能生物材料的目标。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，建立可在敏感生物系统（如细胞，酶和其他生物实体）背景下编程的多功能自组装控制新系统。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，纳米涂层细胞将在临床和生物技术应用中得到应用，其中细胞暴露于各种压力下，包括蛋白水解酶、免疫攻击或生物反应器、宿主、注射递送或3D生物打印过程中的流体动力学力。这项工作还将为在材料科学和细胞/组织工程技术方面培训代表性不足的少数群体提供重点。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.