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: 10380790
• 负责人: Russell R. Reid
• 金额: $ 46.28万
• 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/10380790
• 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细胞 由成骨和皮肤发生的线索诱导的细胞。此外，将工程细胞递送到 3D打印的“智能”支架适合任何形状，将成为快速修复战场的理想方法 受伤我们的总体目标是研究BMP-9诱导的、Notch通路协同的人成年 衍生的尿液干细胞接种到独特的聚柠檬酸-石墨烯混合支架上，以治愈临界尺寸的多 大鼠头皮/颅骨中的组织缺损。该项目是基于这样的假设，即BMP-9- Notch诱导的干细胞成骨及可容纳干细胞的三维支架 沿着成骨和成皮谱系的分化将导致临界大小的 颅面多组织缺损为了验证这一假设，提出了以下具体目标：1） 研究BMP 9诱导人尿祖干细胞（HUP）修复创伤的机制- 2）开发结构复合支架，可以定制，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。这些具体目标将在 1）用转导的iHUP处理临界大小的大鼠颅骨缺损 和通过Notch抑制消除缺陷愈合;和2）3D可打印材料的设计和并入， 使用micro-CLIP技术的mPOC-石墨烯/A5 G81-PPCN杂化支架和支架的测试 一种新的多组织大鼠头皮-颅骨缺损的排列。