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

项目摘要 一种诱人的骨和软组织再生方式包括使用多能间充质干细胞 由成骨和生皮信号诱导的细胞。此外，工程细胞在体内的输送 3D打印的“智能”脚手架为任何形状量身定做，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途径协同人类成人-BMP-9的能力。 将衍生的尿液干细胞种植到独特的多柠檬酸-石墨烯杂化支架上，以修复临界大小的多个 大鼠头皮/头盖骨的组织缺损。这个项目是基于这样一个假设：BMP-9- Notch诱导的干细胞成骨及其可承载干细胞三维支架 沿成骨和皮源性谱系分化将导致临界大小的适当重建 多组织颅面缺损。为了验证这一假设，提出了以下具体目标：1) 探讨BMP9诱导人尿祖干细胞修复创伤的机制 体内诱导颅骨缺损；2)开发可定制的结构复合支架，以适应和 在啮齿动物模型上再生临界大小的皮肤和骨缺损。这些具体目标将得到解决 通过以下实验设计：1)转导iHUPs治疗大鼠临界颅骨缺损 使用BMP9和取消凹槽抑制的缺损性愈合；2)3D可打印的设计和整合 微夹技术制备MPOC-石墨烯/A5G81-PPCN杂化支架及支架测试 一种新的多组织大鼠头颅骨缺损的排列。

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.