Nanoparticle Loaded Biomaterial Scaffolds For Bone Regeneration

用于骨再生的纳米颗粒负载生物材料支架

• 批准号: 1802061
• 负责人: Seth Donahue
• 金额: $ 32.96万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1802061&HistoricalAwards=false
• 关键词: Nanoparticle; Loaded; Biomaterial; Scaffolds; Bone

The goal of this interdisciplinary project is to design a materials-based approach to gene therapy that improves the healing of large bone defects. More than 2 million orthopedic procedures per year use bone grafts to repair damaged bone, at a cost exceeding $30 billion. Despite this need, there are limited supplies of bone tissue for grafts. Recombinant (artificially produced) proteins can be used as an alternative to grafts, but they are expensive and have potential adverse side effects. In collaboration with researchers in Northern Ireland and the Republic of Ireland, this research will develop innovative gene-activated materials that encourage the body's own cells to produce the proteins needed for bone tissue repair. This will advance the nation's health and promote the progress of science by developing material systems that can be used to promote the healing of many tissues in the body, in addition to bone. The educational outreach component of this proposal will help students understand how biological materials behave mechanically and how this knowledge can be used to develop replacement materials for clinical use. Interactive STEM research kits will be developed for middle and high school students to enhance understanding of the measurement techniques used to quantify mechanical behavior of biological materials, including bone and synthetic materials used to replace biological materials clinically.The overall goal of this project is to design a materials-based approach for the controlled delivery of novel osteoanabolic genetic cargos using non-viral vectors combined with osteoconductive scaffolds to promote healing of large bone defects. To achieve this goal, a hybrid material system will be designed and validated; the system will consist of a peptide vector to deliver genetic cargo and a collagen/hydroxyapatite scaffold to present the genetic cargo to cells in the healing space and provide osteoconductive surfaces. The material system will be validated by assessing its ability to promote bone formation activity in vitro and bone healing in vivo. The novel therapeutic genetic cargos for local delivery are parathyroid hormone (PTH), microRNA 26A mimic (miR-26a), and an inhibitor to microRNA133a (antagomiR-133a). The RALA peptide is a non-viral vector that will be used to deliver the therapeutic cargos using a collagen-based scaffold designed specifically for bone repair. The efficacy of the gene activated scaffolds at promoting osteoanabolic activity in mesenchymal stem cells in vitro will be evaluated by quantifying gene expression of key osteogenic and angiogenic markers. The safety of the gene-activated scaffolds will be evaluated in vivo by assessing the distribution of the genetic cargos in tissues and organs. The efficacy will be evaluated by quantifying bone formation in a critical size femoral defect using micro-computed tomography and histomorphometry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个跨学科项目的目标是设计一种基于材料的基因治疗方法，以改善大骨缺损的愈合。每年有超过200万例骨科手术使用骨移植物修复受损骨骼，成本超过300亿美元。尽管有这种需要，但用于移植的骨组织供应有限。重组（人工生产的）蛋白质可以用作移植物的替代品，但它们价格昂贵，并且具有潜在的不良副作用。这项研究将与北方爱尔兰和爱尔兰共和国的研究人员合作，开发创新的基因激活材料，鼓励人体自身细胞产生骨组织修复所需的蛋白质。这将通过开发可用于促进除骨骼外的身体许多组织愈合的材料系统来促进国民健康并促进科学进步。该提案的教育推广部分将帮助学生了解生物材料的机械性能，以及如何利用这些知识开发临床使用的替代材料。将为初中和高中学生开发交互式STEM研究工具包，以提高对用于量化生物材料力学行为的测量技术的理解，包括骨和合成材料，用于替代临床上的生物材料。该项目的总体目标是设计一种基于材料的方法，用于控制递送新型骨合成代谢遗传货物，病毒载体与骨传导支架组合以促进大骨缺损的愈合。为了实现这一目标，将设计并验证混合材料系统;该系统将由肽载体和胶原/羟基磷灰石支架组成，肽载体用于递送遗传货物，胶原/羟基磷灰石支架用于将遗传货物呈递给愈合空间中的细胞并提供骨传导表面。将通过评估其促进体外骨形成活性和体内骨愈合的能力来验证材料系统。用于局部递送的新型治疗性遗传货物是甲状旁腺激素（PTH）、microRNA 26 A模拟物（miR-26 a）和microRNA 133 a的抑制剂（miR-133 a）。RALA肽是一种非病毒载体，将用于使用专门为骨修复设计的基于胶原蛋白的支架递送治疗性货物。将通过定量关键成骨和血管生成标志物的基因表达来评价基因活化支架在体外促进间充质干细胞中骨合成代谢活性的功效。将通过评估组织和器官中遗传货物的分布来评价基因活化支架的体内安全性。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。