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: 1854387
• 负责人: Seth Donahue
• 金额: $ 32.96万
• 依托单位: University of Massachusetts Amherst
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1854387&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，以促进大型骨缺损的愈合。每年有200多万例整形外科手术使用骨移植修复受损的骨骼，费用超过300亿美元。尽管有这种需求，但用于移植的骨组织供应有限。重组(人工生产的)蛋白质可以作为移植物的替代品，但它们价格昂贵，而且有潜在的不良副作用。这项研究将与北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之外的身体许多组织的愈合的材料系统，来促进国家的健康和促进科学的进步。这项提案的教育推广部分将帮助学生了解生物材料的机械行为，以及如何利用这些知识来开发临床使用的替代材料。将为初中生开发交互式STEM研究试剂盒，以提高对用于量化生物材料(包括骨和临床上用于替代生物材料的合成材料)力学行为的测量技术的理解。该项目的总体目标是设计一种基于材料的方法，使用非病毒载体和骨传导支架相结合的方法来控制输送新型骨合成代谢基因货物，以促进大型骨缺损的愈合。为了实现这一目标，将设计和验证一种混合材料系统；该系统将包括一个运送基因货物的多肽载体和一个胶原/羟基磷灰石支架，将基因货物呈现给愈合空间中的细胞并提供骨传导表面。该材料系统将通过评估其在体外促进骨形成活性和在体内促进骨愈合的能力来验证。用于局部传递的新型治疗性遗传货物是甲状旁腺激素(PTH)、模拟microRNA26A(miR-26a)和microRNA133a的抑制剂(antagomiR-133a)。Rala多肽是一种非病毒载体，将使用专门为骨修复设计的胶原基支架来运送治疗性货物。基因激活支架在体外促进间充质干细胞的骨合成代谢活性的有效性将通过量化关键的成骨和血管生成标记的基因表达来评估。基因激活支架的安全性将通过评估基因货物在组织和器官中的分布来在体内进行评估。疗效将通过使用微型计算机断层扫描和组织形态计量学对关键大小的股骨缺损处的骨形成进行量化来评估。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

The osteogenic and angiogenic potential of microRNA-26a delivered via a non-viral delivery peptide for bone repair

• DOI: 10.1016/j.jconrel.2023.09.006
• 发表时间: 2023-09-09
• 期刊: JOURNAL OF CONTROLLED RELEASE
• 影响因子: 10.8
• 作者: Chambers，Phillip;Ziminska，Monika;Mccarthy，Helen O.
• 通讯作者: Mccarthy，Helen O.