A Novel 3D Bioprinted Smart Vascularized Nano Tissue

描述（由申请人提供）：作为一种新兴的组织/器官制造技术，生物3D打印在推动功能性组织/器官替代的发展方面已经开始显示出巨大的希望。然而，目前3D生物打印组织和器官的最大挑战是创建一个高效的3D灌注血管网络，结合天然细胞群募集，以充分整合宿主。到目前为止，还没有成功的植入式生物3D打印血管支架用于组织或器官再生。因此，本研究的目的是在含有生物启发纳米生物材料的组织基质中3D打印高度创新的3D灌注智能血管网络，以改善新生血管和组织形成。我的总体设计包括两个层面的仿生策略，包括建筑设计和改善血管化和骨形成的纳米材料：(1)仿生3D生物打印灌注微血管网络和(2)基于dna的纳米生物活性因子/药物输送系统。具体来说，3D生物打印的灌注微血管网络将在营养物质的有效运输和促进组织形成方面发挥关键作用。自组装纳米材料递送系统旨在以精确控制的方式在时空上原位递送血管生成因子和成骨因子以及疏水干细胞有利药物。“智能”一词源于用于微血管网络的形状记忆材料，通过智能自组装纳米材料，可轻松调节生物3D打印的微观到宏观结构和多种生物活性因子的时空组织，以实现持续的血管化骨功能恢复。我们期望该项目如果成功，不仅对临床骨治疗，而且对其他复杂的组织/器官再生，以及物理和生命科学研究都将产生深远的影响。

DESCRIPTION (provided by applicant): As an emerging tissue/organ manufacturing technique, 3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, the biggest current challenges in 3D bioprinted tissues and organs are to create a highly efficient 3D perfused vascular network, in combination with native cell population recruitment, for adequate host integration. As of yet, there has not been a successful implantable 3D bioprinted vascularized scaffold for tissue or organ regeneration. Thus, the objective of this study is to 3D bioprint a highly innovative 3D perfused smart vascular network within a tissue matrix containing biologically-inspired nanobiomaterials for improved neovascularization and tissue formation. My overall design consists of two levels of biomimetic strategies, including architecture design and nanomaterial for improved vascularization and bone formation: (1) biomimetic 3D bioprinted perfused microvascular network and (2) DNA-based nano bioactive factor/drug delivery system. Specifically, the 3D bioprinted perfused microvascular network will play a key role in the efficient transport of nutrients and promotion of tissue formation. The self- assembling nanomaterial delivery system aims to spatiotemporally co-deliver angiogenic and osteogenic factors as well as hydrophobic stem cell-favorable drugs in a precisely controlled manner in situ. The term "smart" originates from the shape memory material used for our microvascular network, easily tunable 3D bioprinted micro to macro architecture and spatiotemporal organization of multiple bioactive factors via intelligent self-assembling nanomaterials for sustained vascularized bone function recovery. We expect that this project will have a far-reaching impact on not only clinical bone treatment but also other complex tissue/organ regeneration, as well as physical and life science research, if successful.