ABSTRACT

Non-Technical: This award by the National Science Foundation to Stevens Institute of Technology is to explore a sacrificial template-guided approach for generating functional vascular networks that can be used to form vascularized tissue constructs. Every year thousands of patients wait for organ transplantation, however, limited by donors, many of them cannot be treated in time. In recognition, the idea of creating tissue-engineered tissues/organs represents a promising solution. Along with extensive progresses in tissue engineering, effective generation of a functional vasculature network within an engineered tissue becomes the most prominent technical hurdle, which not only restricts from the creation of large volume tissues/organs but also limits their survival after implantation. In this regard, this proposal will provide a controllable method to form the microvascular networks with a high potential to be integrated with tissue-engineered constructs. As such, this project will help to facilitate the development of robust and effective platforms for generating large tissues/organs with complex and hierarchical structures for foreseeable applications in reconstructive surgery and other health care, aside from a wealth of knowledge to advance the rapidly growing fields of tissue engineering and regenerative medicine. With regard to the broader impacts, this project will provide the exciting, inspiring and collaborative research experience to: 1) graduate students via working in an interdisciplinary environment; 2) undergraduate students through the Stevens Scholars and Innovation & Entrepreneurship programs; and 3) high school students through the American Chemical Society's Summer Research Internship Program for Economically Disadvantaged High School Students.


Technical: With this award, the investigators will in vitro reconstruct a functional microvascular network (< 100 micrometers in diameter), closely mimicking the functional characteristics and hierarchical organization of the native one, for vascularization of tissue constructs. To form the microvascular networks with controlled patterns and diameters, especially the desired patency, sacrificial templates of various microfiber networks will be used to support the respective formation of capillary- and arteriole/venule-like networks from vascular cells. The specific objectives of this project are to: (1) investigate the utility of localized-dissolution patterned microfiber networks (5-30 micrometers in diameter) as the sacrificial template for capillary-like vascular network formation, (2) explore the use of near-field electrostatic printed microfiber networks with well controlled patterns and fiber diameters (tunable between 30 and 80 micrometers) as the sacrificial template for arteriole-like structure formation, and (3) form a hierarchical and functional microvascular network in 3D tissue constructs. Successful execution of the proposed research will: (1) gain further insights on the matrix-regulated reversal of endothelial polarity and lumen development; (2) understand the fusion mechanism of existing vascular networks; and (3) establish a strong knowledge base for potential exploitation of the template-enabled vascularization concept to form large implantable 3D tissues, a significant leap forward in tissue engineering and vascular biology.

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