Multifunctional Tropoelastin-Silk Biomaterial Systems

多功能原弹性蛋白-丝生物材料系统

基本信息

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
项目类别：
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

项目摘要

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，可降解的聚合物生物材料系统，可以根据特定的细胞和体内和组织的需求量量身定制。尽管蛋白质 - 蛋白质复合材料主导了组织的结构和功能，但我们无法概括新生物材料的体外复杂性和控制，以指导细胞和组织功能。例如，可以形成机械耐用且耐用的生物材料以产生高度柔韧性和动态生物材料的物质系统仍然是一个挑战。我们的目标是构建一组复合蛋白生物材料，这些材料可以涵盖一系列物理特性，以模仿各种组织结构的弹性以及控制生物学功能的结果能力，例如指导干细胞反应。假设是，具有坚固，耐用蛋白质（丝绸）的高度弹性和动态结构蛋白（Tropoelastin）的组合将生成新的多功能蛋白质复合系统，这些蛋白质复合系统可以为生物材料领域提供广泛的实用性平台。我们建议基于这两种良好的结构蛋白，Tropoelastin和silk的组合，生成一个高度可控制的复合纤维蛋白系统的新家族，这都是可生物降解的蛋白质聚合物，具有良好的生物相容性。这些蛋白质包括一系列生物材料需求； Tropoelastin提供了高度柔韧性和动态的结构特征，丝绸提供机械韧性和缓慢的降解。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建议的基础。实验计划的重点是：（a）进一步阐明热带素和丝之间的机械相互作用，以优化对材料结构和功能的控制，（（b）评估细胞相互作用的材料范围，以理解蛋白质复合材料，材料合规性和使用hMSCS和皮质神经元和材料及其反应的材料合规性和细胞之间的关系，以及（通过这些系统可以实现的动态材料特性的利用来支持细胞功能在体外。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生成所需材料（Tropoelastin，silks）的能力，使材料（例如表面化学）的功能功能，以探测两个组件之间与机械洞察力之间的相互作用，以将蛋白质与新材料格式处理为新的材料，并与这些材料相关的材料，并将其处理为涉及这些材料的互联材料。计划的总体结果将是一个新的蛋白质复合生物材料平台，它将满足生物材料领域的重要需求，与坚固但灵活的系统和强，耐用的系统直接相关。