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 骨骼和软组织再生的一种有吸引力的方式涉及使用多能间质茎 由成骨和皮肤提示诱导的细胞。此外，在 根据任何形状量身定制的3D打印的“智能”脚手架将成为快速维修战场的理想方法 受伤。我们的总体目标是研究BMP-9诱导的，缺口途径 - 杂交的人类的能力 衍生的尿液干细胞播种到独特的多二乙烯酸酯杂化型支架上，以治愈关键尺寸的多种 大鼠头皮/颅骨的组织缺陷。该项目基于以下假设：BMP-9-的结合 Notch诱导的干细胞成骨和能够托管干细胞的三维支架 沿成骨和皮肤谱系的分化将导致对关键大小的足够重建 多组织颅面缺陷。为了检验该假设，提出了以下特定目的：1） 研究BMP9诱导人类尿液祖细胞（HUP）修复创伤的机制 体内诱发颅骨缺陷； 2）开发可定制以适合和的结构复合支架 在啮齿动物模型中再生临界尺寸的皮肤和骨膜缺陷。这些具体目标将被解决 通过以下实验设计：1）用IHUP翻译的临界大小的大鼠颅骨缺陷处理 通过BMP9和缺陷愈合，并通过缺陷抑制作用和； 2）设计并纳入3D打印机 MPOC-Graphene/A5G81-PPCN混合脚手架使用微型剪辑技术和脚手架的测试 新型多组织大鼠头皮颅内缺陷中的排列。