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.

Public Health Relevance

Complex tissue and organ regeneration represents a significant clinical problem worldwide due to a shortage of donor tissues/organs as well as complications associated with current implants and procedures. This project is expected to provide an exciting and significant step toward successfully using a custom designed vascularized nano tissue construct to treat large tissue (such as craniofacial or spinal bone) defects in a clinical setting. It may provide a durable, easy- to-use, biocompatible life-long solution for patients.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
NIH Director’s New Innovator Awards (DP2)
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Special Emphasis Panel (ZRG1-MOSS-C (56))
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Hunziker, Rosemarie
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George Washington University
Schools of Engineering
United States
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Miao, Shida; Cui, Haitao; Nowicki, Margaret et al. (2018) Photolithographic-stereolithographic-tandem fabrication of 4D smart scaffolds for improved stem cell cardiomyogenic differentiation. Biofabrication 10:035007
Cui, Haitao; Miao, Shida; Esworthy, Timothy et al. (2018) 3D bioprinting for cardiovascular regeneration and pharmacology. Adv Drug Deliv Rev 132:252-269
Zhu, Wei; Webster, Thomas J; Zhang, Lijie Grace (2018) How can 3D printing be a powerful tool in nanomedicine? Nanomedicine (Lond) 13:251-253
Nowicki, Margaret; Castro, Nathan J; Rao, Raj et al. (2017) Integrating three-dimensional printing and nanotechnology for musculoskeletal regeneration. Nanotechnology 28:382001
Miao, Shida; Castro, Nathan; Nowicki, Margaret et al. (2017) 4D printing of polymeric materials for tissue and organ regeneration. Mater Today (Kidlington) 20:577-591
Cui, Haitao; Nowicki, Margaret; Fisher, John P et al. (2017) 3D Bioprinting for Organ Regeneration. Adv Healthc Mater 6:
Heo, Dong Nyoung; Castro, Nathan J; Lee, Se-Jun et al. (2017) Enhanced bone tissue regeneration using a 3D printed microstructure incorporated with a hybrid nano hydrogel. Nanoscale 9:5055-5062
Zhu, Wei; Castro, Nathan J; Cui, Haitao et al. (2016) A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions. Nanotechnology 27:315103
Cui, Haitao; Zhu, Wei; Nowicki, Margaret et al. (2016) Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs via Dual 3D Bioprinting: Integrating Regional Bioactive Factors into Architectural Design. Adv Healthc Mater 5:2174-81
Miao, Shida; Zhu, Wei; Castro, Nathan J et al. (2016) Four-Dimensional Printing Hierarchy Scaffolds with Highly Biocompatible Smart Polymers for Tissue Engineering Applications. Tissue Eng Part C Methods 22:952-963

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