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