Self-assembling Peptide Nanofiber Hydrogels for Delivery of Proteins and Cells

用于输送蛋白质和细胞的自组装肽纳米纤维水凝胶

• 批准号: 8578076
• 负责人: Rena N. D'Souza
• 金额: $ 36.97万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8578076
• 关键词: Amino Acid Sequence; Amino Acid Substitution; Architecture; Area; Biodegradation; Biomimetics; Cell Adhesion; Cell Culture Techniques; Cell Line; Cell Proliferation; Cells; Cellular biology; Charge; Chemicals; Chemistry; Clinical; Clinical Trials; Complex; Cues; Data; Dental; Dental Pulp; Dentin; Dentistry; Encapsulated; Engineering; Environment; Extracellular Matrix; Fiber; Future; Gel; Goals; Growth Factor; Height; Human; Hydrogels; Injectable; Ionic Strengths; Left; Length; Mechanics; Mediating; Medical Research; Methods; Mus; Nanostructures; Nanotechnology; Natural regeneration; Organ; Peptides; Pharmaceutical Preparations; Play; Property; Proteins; Recovery; Research Personnel; Role; Science; Series; Site; Stem cells; Surface; Syringes; Testing; Time; Tissue Engineering; Tissues; Tooth structure; Translational Research; Transplantation; Variant; Width; Work; base; controlled release; crosslink; design; flexibility; in vivo; in vivo regeneration; interdisciplinary approach; nano; nanofiber; nanostructured; novel; programs; regenerative; response; scaffold; self assembly; small molecule; success; synthetic protein; tissue regeneration

DESCRIPTION (provided by applicant): This proposal develops a nanostructured mimic of extracellular matrix prepared from a self-assembling peptide we call "Multidomain Peptides" or MDPs. The MDPs self-assemble into nanofibers that can be triggered to form a hydrogel. Because the peptides are easy to prepare and have a well defined design criteria many variations on the MDP architecture can be prepared which allow us to tailor 1) the conditions under which the fibers self-assemble (including conditions compatible with cell culture and in vivo applications), 2) the mechanical properties critical for handling and injectability, 3) the presentation of chemical information for cells, and 4) controlled biodegradation. This exceptional combination of properties will be developed here to create biomimetic scaffolds for the entrapment and delivery of cells, proteins and small molecule drugs. Our work will culminate with an in vivo application which uses this nanostructured hydrogel for dental regeneration. It is expected that the nanofibers will prove to be suitable as an injectable, localized, simultaneous delivery method for cells, proteins and small molecule drugs which will actively assist in directing cellular activity. Finally, after the MDP matrix has played its role it will degrade leaving behind only regenerated tissue. Such a matrix will play a critical role in future tissue engineering strategies (including, but not limited to, dental regeneration) which require a smart scaffolding material to organize the constituent cells and drugs until the body's own regenerative ability can take over. Our proposal is organized into four aims. Aim 1 will determine the design, flexibility and methods used to prepare MDP nanofibers. Aim 2 will optimize MDP nanofibers for three dimensional cell entrapment, cell delivery and cell mediated biodegradation. Aim 3 will develop a series of nanofibrous gels which will deliver growth factors and other small molecules localized in time and space. Aim 4 will test the above developed nanofibrous hydrogels ability to promote dental regeneration in vivo. This highly translational research will apply novel tissue engineering and nanotechnology concepts to the design of multidomain peptide hydrogels intended as an all-purpose scaffold for the regeneration tissue (tested here on the regeneration of the dentin-pulp complex). By combining expertise in chemistry, materials sciences, nanotechnology, cell biology and clinical dentistry we will generate data that will provide the framework for further studies testing these hydrogels in human clinical trials.

描述（由申请人提供）：该提案开发了一种细胞外基质的纳米结构模拟物，由我们称为“多域肽”或 MDP 的自组装肽制备。 MDP 自组装成纳米纤维，可以触发纳米纤维形成水凝胶。由于肽易于制备并且具有明确的设计标准，因此可以制备 MDP 架构的许多变体，这使我们能够定制 1) 纤维自组装的条件（包括与细胞培养和体内应用兼容的条件） ），2）对于操作和可注射性至关重要的机械性能，3）细胞化学信息的呈现，以及4）受控生物降解。这种特殊的特性组合将在这里开发，以创建用于捕获和递送细胞、蛋白质和小分子药物的仿生支架。我们的工作将在体内应用中达到顶峰，该应用使用这种纳米结构水凝胶进行牙齿再生。预计纳米纤维将被证明适合作为细胞、蛋白质和小分子药物的可注射、局部、同时递送方法，这将积极协助指导细胞活动。最后，MDP基质发挥作用后会降解，仅留下再生组织。这种基质将在未来的组织工程策略（包括但不限于牙齿再生）中发挥关键作用，该策略需要智能支架材料来组织组成细胞和药物，直到人体自身的再生能力能够接管。我们的建议分为四个目标。目标 1 将确定用于制备 MDP 纳米纤维的设计、灵活性和方法。目标 2 将优化 MDP 纳米纤维，用于三维细胞捕获、细胞递送和细胞介导的生物降解。 Aim 3 将开发一系列纳米纤维凝胶，将生长因子和其他小分子定位在时间和空间上。目标4将测试上述开发的纳米纤维水凝胶在体内促进牙齿再生的能力。 这项高度转化的研究将应用新颖的组织工程和纳米技术概念来设计多域肽水凝胶，该水凝胶旨在作为再生组织的通用支架（此处针对牙本质-牙髓复合物的再生进行测试）。通过结合化学、材料科学、纳米技术、细胞生物学和临床牙科方面的专业知识，我们将生成数据，为在人体临床试验中测试这些水凝胶的进一步研究提供框架。