Recent advances in rapid prototyping methods including stereolithography and nozzle-based bioprinting have enabled manufacturing of complex structures with controlled architectures and tunable properties. With their capability of patient-specific design and precision engineering, these technologies have impacted many areas such as tissue engineering and regenerative medicine. In tissue engineering, the fabrication of highly organized, functional three-dimensional (3D) constructs that mimic the complex architecture of various organs is of great importance. Towards this goal, different rapid prototyping strategies based on stereolithography and bioprinting have been demonstrated. Despite significant advances, however, the following key challenges for bioprinting biomimetic tissue constructs still remain: a) Current methods for fabricating 3D cell-laden constructs with clinically-relevant precision require time-scales that induce cell death. b) Multicomponent/multicellular tissue constructs with biologically-relevant architectures and characteristics are difficult or impossible to bioprint at present. To address both of these challenges simultaneously, we plan to develop a Rapid, Multimaterial Bioprinting (RMB) technology. The novel RMB approach is significantly faster than conventional 3D bioprinting and produces multicomponent complex architectures using diverse cell-laden biomaterials continuously. Therefore, this novel 3D bioprinting system can be used to build biomimetic tissues, such as pre-vascularized cardiac tissue with blood vessels ranging from larger anastomosable vessels to smaller capillaries. We will integrate a programmable microfluidic system with a dynamic optical printing method to deliver different cell types and gel precursors to mimic the biomechanical characteristics and compositions of the cardiac tissue. Specifically, we will incorporate iPS cell-derived human cardiomyocytes (iCMs) and endothelial cells (ECs) with designed spatial distributions in the engineered tissue constructs. We will then assess the maturation of the pre- vascularized cardiac tissues in vitro and examine the biocompatibility and functionality of the bioprinted vascular networks in a subcutaneous implantation model in nude rats. The completion of this work will be a paradigm shift and a landmark achievement in efforts towards clinical treatments of vascularized cardiac tissue.

Public Health Relevance

This project seeks to develop a novel three-dimensional (3D) bioprinting method to create vascularized cardiac tissues. Results from this work will pave the road for developing biological substitutes for damaged myocardium, which lacks the intrinsic regenerative capability. This advanced technology can also have a significant economical impact as heart diseases are responsible for ~17 million deaths per year globally and imposes a staggering annual cost of $300 billion on the health care system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB021857-04
Application #
9676272
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Rampulla, David
Project Start
2016-07-01
Project End
2020-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Engineering (All Types)
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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