The long term goal of our research is to design complex biomaterial scaffolds that can mimic the micro- architecture of cardiac tissues and to augment regeneration therapies. These tissue-like structures will have the appropriate microarchitectural features of native tissues including a functioning vasculature. To fabricate these tissues we are interested in using natural molecules such as hyaluronic acid (HA;also called hyaluronan)-based biomaterials, because of the ubiquitous presence of HA in the extracellular matrix (ECM) of tissues and the significant role that HA inherently plays in wound healing. The objective of the proposed research is to develop methods to create 3D scaffolds of native ECM components with complex internal architecture and cell encapsulation. To fabricate such scaffolds, we will develop an innovative direct-write platform based on a projection-style stereolithographic (SL) method, coined as PSL.
In Specific Aim 1, we will develop and optimize the PSL system for the fabrication of 3D microstructures using HA with Arg-Gly-Asp (RGD) and matrix metalloproteinase (MMP).
In Specific Aim 2, we will use PSL for Direct-write 3D HA scaffolds encapsulating cardiomyocytes.
In Specific Aim 3, we will create vascularized structures in a 3D scaffold and analyze vasculature functions. We will seed an endothelial cell lining within microchannels. The seeding process will be optimized by adjusting the cell seeding density and duration as well as surface chemistry. The vascular function and biomechanical properties of these engineered tissue constructs will be determined in vitro.

Public Health Relevance

This project seeks to develop a novel biofabrication platform to create three-dimensional (3D) scaffolds of native extracellular matrix components with complex internal architectures and cell encapsulation. The goal of the project is to create vascularized structures in the 3D scaffolds

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB012597-02
Application #
8146914
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Hunziker, Rosemarie
Project Start
2010-09-30
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$360,091
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
Saghazadeh, Saghi; Rinoldi, Chiara; Schot, Maik et al. (2018) Drug delivery systems and materials for wound healing applications. Adv Drug Deliv Rev 127:138-166
Shin, Su Ryon; Migliori, Bianca; Miccoli, Beatrice et al. (2018) Electrically Driven Microengineered Bioinspired Soft Robots. Adv Mater 30:
Leijten, Jeroen; Seo, Jungmok; Yue, Kan et al. (2017) Spatially and Temporally Controlled Hydrogels for Tissue Engineering. Mater Sci Eng R Rep 119:1-35
González-González, Everardo; Alvarez, Mario Moisés; Márquez-Ipiña, Alan Roberto et al. (2017) Anti-Ebola therapies based on monoclonal antibodies: current state and challenges ahead. Crit Rev Biotechnol 37:53-68
Zhang, Yu Shrike; Aleman, Julio; Shin, Su Ryon et al. (2017) Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc Natl Acad Sci U S A 114:E2293-E2302
Naseer, Shahid M; Manbachi, Amir; Samandari, Mohamadmahdi et al. (2017) Surface acoustic waves induced micropatterning of cells in gelatin methacryloyl (GelMA) hydrogels. Biofabrication 9:015020
Zhu, Kai; Shin, Su Ryon; van Kempen, Tim et al. (2017) Gold Nanocomposite Bioink for Printing 3D Cardiac Constructs. Adv Funct Mater 27:
Sadeghi, Amir Hossein; Shin, Su Ryon; Deddens, Janine C et al. (2017) Engineered 3D Cardiac Fibrotic Tissue to Study Fibrotic Remodeling. Adv Healthc Mater 6:
Ribas, João; Zhang, Yu Shrike; Pitrez, Patrícia R et al. (2017) Biomechanical Strain Exacerbates Inflammation on a Progeria-on-a-Chip Model. Small 13:
Yang, Jingzhou; Zhang, Yu Shrike; Yue, Kan et al. (2017) Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta Biomater 57:1-25

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