Multifunctional Tropoelastin-Silk Biomaterial Systems

多功能原弹性蛋白-丝生物材料系统

• 批准号: 8518096
• 负责人: DAVID L. KAPLAN
• 金额: $ 27.74万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518096
• 关键词: Address; Binding; Biocompatible; Biocompatible Materials; Biological; Biological Process; Bone Marrow; Carbodiimides; Cell Communication; Cell physiology; Cells; Chemicals; Chemistry; Clinical; Collagen; Coupling; Data; Elasticity; Environment; Extracellular Matrix; Family; Fiber; Fibronectins; Film; Genotype; Goals; Growth; Human; Hyaluronic Acid; In Vitro; Inflammatory Response; Mechanics; Modification; Molecular; Morphology; Muscle Cells; Neurons; Outcome; Polymers; Process; Property; Proteins; Reaction; Regenerative Medicine; Signal Transduction; Silk; Source; Stem cells; Stretching; Structural Protein; Structure; Supporting Cell; Surface; System; Tissues; Tropoelastin; base; biomaterial compatibility; crosslink; fibrous protein; flexibility; human tissue; improved; in vivo; insight; molecular scale; novel; osteogenic; physical property; response; stem cell fate; success

DESCRIPTION (provided by applicant): New multifunctional, degradable, polymeric biomaterial systems are needed that can be tailored to specific cell and tissue needs in vitro and in vivo. While protein-protein composites dominate tissue structure and function in our bodies, we have been unable to recapitulate the complexity and control of such systems in vitro for new biomaterials in order to direct cell and tissue functions. For example, material systems that can form mechanically robust and durable biomaterials to give highly flexible and dynamic biomaterials, remains a challenge. Our goal is to construct a panel of composite protein biomaterials that can cover a range of physical properties, to mimic the elasticity of diverse tissue structures and the consequential ability to control biological function - such as to direct stem cell responses. The hypothesis is that combinations of a highly elastic and dynamic structural protein (tropoelastin) with tough, durable proteins (silk) will generate new multifunctional protein composite systems that can offer a broad platform of utility to the biomaterials field. We propose to generate a new family of highly controllable composite fibrous protein systems, based on combinations of these two well-established structural proteins, tropoelastin and silk, both biodegradable protein polymers with good biocompatibility. These proteins encompass a range of biomaterial needs; tropoelastin provides highly flexible and dynamic structural features, silk provides mechanical toughness and slow degradation. Our findings of molecular-scale interactions between these two structural proteins, forms the basis of the present proposal. The experimental plans are focused on: (a) further elucidation of the mechanistic interactions between tropoelastin and silk to optimize control of material structure and function, (b) assessment of cell interactions for the range of materials generated to understand relationships between the protein composites, material compliance and cell outcomes, using hMSCs and cortical neurons, and in vivo screens of material degradation profiles and inflammatory responses, and (c) exploitation of the dynamic material properties achievable with these systems towards support of cell functions in vitro. The experimental plans are supported by extensive preliminary data that demonstrate our ability to generate the required materials (tropoelastin, silks), to functionalize the materials (e.g., surface chemistry),to probe the interactions among the two components with mechanistic insight, to process the proteins into new material formats, and to direct cell outcomes on these materials with outcomes dependent on the composition. The overall outcome from the plans would be a new protein composite biomaterials platform that would fill an important need in the field of biomaterials, with direct relevance to tough but flexible systems and strong, durable systems.

描述（由申请人提供）：需要新的多功能、可降解、聚合生物材料系统，该系统可以根据体外和体内特定细胞和组织的需求进行定制。虽然蛋白质-蛋白质复合物主导着我们体内的组织结构和功能，但我们无法在体外为新生物材料概括此类系统的复杂性和控制，以指导细胞和组织功能。例如，能够形成机械坚固耐用的生物材料以提供高度灵活和动态的生物材料的材料系统仍然是一个挑战。我们的目标是构建一组复合蛋白质生物材料，该材料可以涵盖一系列物理特性，以模拟不同组织结构的弹性以及控制生物功能的相应能力 - 例如指导干细胞反应。假设将高弹性和动态结构蛋白（弹性蛋白原）与坚韧、耐用的蛋白质（丝）结合起来将产生新的多功能蛋白质复合系统，为生物材料领域提供广泛的实用平台。我们建议基于这两种成熟的结构蛋白原弹性蛋白和丝的组合，产生一个新的高度可控的复合纤维蛋白系统家族，这两种蛋白聚合物都是具有良好生物相容性的可生物降解的蛋白质聚合物。这些蛋白质涵盖了一系列生物材料需求；原弹性蛋白提供高度灵活和动态的结构特征，丝提供机械韧性和缓慢降解。我们对这两种结构蛋白之间分子尺度相互作用的发现构成了本提案的基础。实验计划的重点是：（a）进一步阐明弹性蛋白原和丝之间的机械相互作用，以优化材料结构和功能的控制，（b）评估所生成的一系列材料的细胞相互作用，以了解蛋白质复合材料之间的关系，材料顺应性和细胞结果，使用 hMSC 和皮质神经元，以及材料降解曲线和炎症反应的体内筛选，以及 (c) 利用这些系统可实现的动态材料特性来支持体外细胞功能。实验计划得到了广泛的初步数据的支持，这些数据证明了我们有能力生成所需的材料（弹性蛋白原、丝）、对材料进行功能化（例如表面化学）、通过机械洞察力探索两种成分之间的相互作用、处理蛋白质转化为新的材料形式，并指导细胞对这些材料的结果，其结果取决于其成分。该计划的总体成果将是一个新的蛋白质复合生物材料平台，该平台将满足生物材料领域的重要需求，与坚韧但灵活的系统和坚固耐用的系统直接相关。