Multi-Tissue Craniofacial Engineering using 3D-BMP9-Notch-Synergized Graphene Citrate Composite Scaffolds

使用 3D-BMP9-Notch-协同石墨烯柠檬酸盐复合支架的多组织颅面工程

• 批准号: 10182818
• 负责人: Russell R. Reid
• 金额: $ 48.22万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10182818
• 关键词: 3-Dimensional; 3D Print; Address; Adenoviruses; Adult; Anatomy; Architecture; Autologous; Biocompatible Materials; Biological; Biomechanics; Biomedical Engineering; Birth trauma; Bone Morphogenetic Proteins; Bone Tissue; Calvaria; Cell Line; Cells; Cephalic; Chicago; Child; Citrates; Citric Acid; Collaborations; Complex; Craniofacial Abnormalities; Cues; Custom; Data; Defect; Engineering; Engraftment; Excision; Experimental Designs; Face; Failure; Goals; Growth; Human; Hybrids; Hydrogels; In Vitro; Individual; Injury; Malignant Neoplasms; Mesenchymal Stem Cells; Methods; Modality; Modeling; Morbidity - disease rate; Mus; Natural regeneration; Notch Signaling Pathway; Operative Surgical Procedures; Osteogenesis; Pathway interactions; Patients; Phase; Pluripotent Stem Cells; Printing; Procedures; Rattus; Reproducibility; Research; Risk; Rodent Model; Scalp structure; Shapes; Signal Transduction; Site; Skeleton; Skin; Solid; Source; Specimen; Structure; Surgeon; Technology; Testing; Time; Tissue Banks; Tissue Differentiation; Tissues; Translational Research; Trauma; Universities; Urine; Work; X-Ray Computed Tomography; Zygomatic bone; base; battlefield injury; bone; bone morphogenetic protein 9; cancer surgery; clinical application; craniofacial structure; craniofacial tissue; cranium; design; functional outcomes; graphene; healing; human subject; implantation; in vivo; infection risk; microCT; notch protein; novel; novel strategies; osteogenic; progenitor; programs; prototype; reconstruction; regenerative; repaired; restoration; scaffold; skeletal; skin regeneration; soft tissue; spatiotemporal; stem cell derived tissues; stem cell differentiation; stem cells; success; tissue regeneration; translational impact; treatment strategy

PROJECT ABSTRACT An attractive modality for bone and soft tissue regeneration involves the use of pluripotent mesenchymal stem cells that are induced by osteogenic and dermogenic cues. Furthermore, the delivery of engineered cells within 3D-printed, “smart” scaffolds tailored to any shape would make an ideal approach to rapidly repair battlefield injuries. Our overall goal is to investigate capacity of BMP-9-induced, Notch pathway-synergized human adult- derived urine stem cells seeded onto unique, polydiocitrate-graphene hybrid scaffolds, to heal critical-sized multi- tissue defects in the rat scalp/cranium. This project is based on the hypothesis that the combination of BMP-9- Notch-induced stem cell osteogenesis and a three-dimensional scaffold capable of hosting stem cell differentiation along osteogenic and dermogenic lineages will lead to adequate reconstruction of critical-sized multi-tissue craniofacial defects. To test this hypothesis, the following specific aims are proposed: 1) To investigate the mechanisms by which BMP9 induced human urine progenitor stem cells (HUPs) repair trauma- induced cranial defects in vivo; 2) To develop structural composite scaffolds that can be customized to fit and regenerate a critical-sized skin and bone calvarial defect in a rodent model. These specific aims will be addressed by the following experimental design: 1) Treatment of critical-sized rat cranial defects with iHUPs transduced with BMP9 and abrogation of defect healing with Notch inhibition and; 2) Design and incorporation of 3D-printable mPOC-graphene/A5G81-PPCN hybrid scaffolds using micro-CLIP technology and testing of scaffold permutations in a novel multi-tissue rat scalp-cranial defect.

项目摘要 骨和软组织再生的一种有吸引力的方式涉及使用多能间充质干 由成骨和皮肤生成信号诱导的细胞此外，还包括工程细胞的递送。 适合任何形状的 3D 打印“智能”脚手架将成为快速修复战场的理想方法 我们的总体目标是研究 BMP-9 诱导的、Notch 通路协同的成人损伤的能力。 将衍生的尿液干细胞接种到独特的聚二柠檬酸盐-石墨烯混合支架上，以治愈临界尺寸的多细胞 该项目基于 BMP-9- 组合的假设。 Notch诱导的干细胞成骨和能够容纳干细胞的三维支架 沿成骨和真皮谱系的分化将导致临界尺寸的充分重建 为了检验这一假设，提出了以下具体目标：1） 研究 BMP9 诱导人尿祖干细胞 (HUP) 修复创伤的机制 2）开发可定制的结构复合脚手架，以适应和 在啮齿动物模型中再生临界尺寸的皮肤和骨颅骨缺损这些具体目标将得到解决。 通过以下实验设计： 1) 用转导的 iHUP 治疗临界尺寸的大鼠颅骨缺损 使用 BMP9 并通过 Notch 抑制消除缺陷愈合；2) 可 3D 打印的设计和结合 使用 micro-CLIP 技术的 mPOC-石墨烯/A5G81-PPCN 混合支架和支架测试 一种新型多组织大鼠头皮颅骨缺损的排列。