A nanostructured approach to complex tissue scaffolds and smart implants

项目摘要/摘要 不断发展的再生医学领域融合了化学、工程学、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将活细胞和适当的生物信号与三维支架材料相结合。 在设计组织支架和植入物的同时，使其能够安全地输送/固定到靶组织并在生理环境中具有适当的长期功能的困难，一直是将再生医学概念转化为临床实践的主要障碍。建议的Eureka项目使用创新的纳米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、明确的生化微环境以及微创输送和自适应组织对接能力。除了设计高形态的有机-无机纳米结构构件来编码丰富的功能信息外，还提出了一种通过限制刚性纳米颗粒锚定之间的聚合物链-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，这一新平台将为设计适用于广泛应用的高性能形状记忆复合材料开辟新的范式。通过产生患者特定和缺陷特定的医疗植入物和组织移植物，这些植入物和组织在物理和生化上精确地适合和符合每个人的缺陷，它将对从骨骼缺陷到心血管疾病和中风等广泛医疗条件的个性化干预产生改变范式的影响。此外，由于这些智能材料能够在空间上呈现和在时间上释放信号分子到三维支架和从三维支架释放出明确的机械线索，这些智能材料还可以实现对复杂分子信号事件的体外信息研究，或者作为有价值的药物发现的三维组织模型。 由于这一概念的新颖性，其固有的风险，以及巨大的医学影响和科学潜力，该项目是尤里卡筹资机制的极佳候选者。在4年的项目期内，我们希望产生一个具有广泛孔隙率的三维形状记忆支架库，机械的 强度和信号分子封装/释放特性，适用于从自适应合成骨移植到可展开药物洗脱支架等应用。我们将使用体外细胞培养模型和小动物临界缺陷模型来验证该纳米结构材料设计平台的可行性，选择承载形状记忆的骨组织支架作为初始概念验证 申请。

Project Summary/Abstract 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.