A nanostructured approach to complex tissue scaffolds and smart implants

描述（由申请人提供）：再生医学的发展领域整合了化学，工程，生物学和医学，以修复，替换或增强因疾病，损伤或衰老而丧失的组织或器官功能。它需要复杂的方法来整合活细胞和适当的生物信号与三维支架材料。设计具有同时使其能够安全递送/牢固配合到靶组织以及其在生理环境中的适当长期功能的性质的组织支架和植入物的困难已经成为将再生医学概念减少到临床实践的主要障碍。拟议的尤里卡项目使用创新的纳米结构材料设计平台来开发形状记忆组织支架和植入物，这些支架和植入物具有可调的机械强度、定义的生化微环境以及微创递送和自适应组织对接能力。除了设计高模态的有机-无机纳米结构构建块来编码丰富的功能信息之外，还提出了一种通过限制刚性纳米颗粒锚之间的聚合物链-链相互作用来增强形状记忆行为的创新策略。如果得到验证，这个新的平台可以为设计高性能形状记忆复合材料提供一个新的范例。通过产生患者特异性和缺陷特异性医疗植入物和组织移植物，这些植入物和组织移植物在物理和生物化学上精确地适应和符合每个个体缺陷，它将对从骨骼缺陷到心血管疾病和中风的广泛医疗状况的个性化干预产生改变模式的影响。此外，由于具有在空间上呈现和在时间上释放信号分子至具有限定的机械线索的三维支架的能力，这些智能材料还可以实现复杂分子信号传导事件的信息性体外研究，或者作为用于药物发现的有价值的三维组织模型。由于这一概念的新奇、其固有的风险以及巨大的医学影响和科学潜力，该项目是尤里卡资助机制的一个很好的候选项目。在4年的项目期内，我们期望产生一个三维形状记忆支架库，该支架具有广泛的孔隙率、机械强度和信号分子包封/释放特性，适用于从自适应合成骨移植物到可展开药物洗脱支架的应用。我们将使用体外细胞培养模型和小动物临界缺损模型来验证这种纳米结构材料设计平台的可行性，选择承重形状记忆骨组织支架作为最初的概念验证应用。公共卫生相关性：设计组织支架和植入物同时使其能够安全递送/牢固地适配到靶组织并使其在生理环境中具有适当的长期功能的困难已经成为将再生医学概念减少到临床实践的主要障碍。拟议的尤里卡项目使用创新的纳米结构材料设计平台来开发形状记忆组织支架和植入物，这些支架和植入物具有可调的机械强度、定义的生化微环境以及微创递送和自适应组织对接能力。如果得到验证，这个新平台可以导致开发患者特定和缺陷特定的医疗植入物和组织移植物，这些植入物和组织移植物在物理和生物化学上精确地适应和符合每个单独的缺陷。它将对从骨骼缺陷到心血管疾病和中风等广泛医疗状况的个性化干预产生改变模式的影响，使数百万美国人受益。

DESCRIPTION (provided by applicant): The evolving field of regenerative medicine integrates chemistry, engineering, biology and medicine to repair, replace, or enhance tissue or organ function lost due to disease, injury, or aging. It requires complex approaches to integrate living cells and proper biological signals with 3-dimensional scaffolding materials. The difficulty in designing tissue scaffolds and implants with properties that simultaneously enable their safe delivery / secure fitting to a target tissue and their proper long-term function in physiological environment has been a major roadblock in reducing regenerative medicine concepts to clinical practices. The proposed EUREKA project uses an innovative nanostructured material design platform to develop shape memory tissue scaffolds and implants that possess tunable mechanical strength, defined biochemical microenvironment, and minimally invasive delivery and self-fitting tissue docking capability. In addition to designing high-modality organic-inorganic nanostructured building blocks to encode rich functional information, an innovative strategy for enhancing shape memory behavior through the confinement of polymer chain-chain interactions between rigid nanoparticle anchors is proposed. If validated, this new platform can open a new paradigm for designing high performance shape memory composites for a wide range of applications. By generating patient-specific and defect-specific medical implants and tissue grafts that precisely fit and conform to each individual defects physically and biochemically, it will have paradigm-changing impact on personalized intervention of a broad range of medical conditions ranging from skeletal defects to cardiovascular diseases and stroke. In addition, with the ability to spatially present and temporally release signaling molecules to and from the 3-dimensional scaffolds with defined mechanical cues, these intelligent materials can also enable informative in vitro studies of complex molecular signaling events or serve as valuable 3-dimensional tissue models for drug discovery. Due to the novelty of this concept, its inherent risks, and enormous medical impact and scientific potential, this project is an excellent candidate for the EUREKA funding mechanism. Within the 4-year project period, we expect to generate a library of 3-dimensional shape memory scaffolds with wide-ranging porosities, mechanical strengths, and signaling molecule encapsulation/release characteristics suitable for applications ranging from self-fitting synthetic bone grafts to deployable drug-eluting stents. We will validate the feasibility of this nanostructured material design platform using both in vitro cell culture models and a small animal critical defect model, choosing a weight-bearing shape memory bone tissue scaffold as the initial proof-of-concept application. PUBLIC HEALTH RELEVANCE: The difficulty in designing tissue scaffolds and implants that simultaneously enable their safe delivery / secure fitting to a target tissue and their proper long-term function in physiological environment has been a major roadblock in reducing regenerative medicine concepts to clinical practices. The proposed EUREKA project uses an innovative nanostructured material design platform to develop shape memory tissue scaffolds and implants that possess tunable mechanical strength, defined biochemical microenvironment, and minimally invasive delivery and self-fitting tissue docking capability. If validated, this new platform can lead to the development of patient-specific and defect-specific medical implants and tissue grafts that precisely fit and conform to each individual defects, physically and biochemically. It will have paradigm-changing impact on personalized intervention of a broad range of medical conditions ranging from skeletal defects to cardiovascular diseases and stroke, benefiting millions of Americans.