Tissue engineering is a potentially powerful method to treat diabetes, heart failure and liver disease. Present tissue engineering approaches generally involve seeding cells onto biodegradable polymeric scaffolds. Current limitations with tissue engineering scaffolds include their inability to generate vascularized tissues, uniformly seed cells throughout the constructs, or mimic the complex cellular microenvironment. We hypothesize that by using the principles of life science, biomaterials science, and microengineering, it will be possible to develop 3D tissue-engineered constructs with controlled microvasculature and tissue architecture. We intend to use cell-laden hydrogels for fabricating microengineered tissue constructs, and to examine the functionality and applicability of these constructs by using cadiomyocytes as a tissue model. We propose a 3-step strategy to accomplish this task. Firstly, we will develop novel hydrogels comprised of natural and biodegradable materials with improved mechanical properties and favorable to cell-encapsulation. Then, we will investigate approaches to engineer the microvasculature within these hydrogels by fabricating an interconnected network of microchannels and macropores. Lastly, we will incorporate additional complexity into the cell-laden hydrogels to generate 3D tissues and replicate the cellular microenvironment.
The specific aims of our project are: 1. To develop methods for fabricating biodegradable hydrogels with controlled mechanical, chemical and biological properties for microscale tissue engineering applications;2. To engineer tissue constructs using cell-laden hydrogels incorporated with a microvasculature comprising of an interconnected network of microchannels and macropores;3. To engineer biological complexity within the microfabricated cell-laden scaffolds to generate functional 3D cardiac tissue constructs. Public Health Relevance Statement (provided by applicant): The development of a novel microscale 3D vascularized tissue engineered constructs have tremendous potential applications in the treatment of many different disease, including heart diseases. We will develop 3D tissues using novel hydrogels and provide vasculature to supply nutrients to the engineered tissue.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZEB1-OSR-D (J1))
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Lundberg, Martha
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Brigham and Women's Hospital
United States
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Bhise, Nupura S; Ribas, João; Manoharan, Vijayan et al. (2014) Organ-on-a-chip platforms for studying drug delivery systems. J Control Release 190:82-93
Cha, Chaenyung; Oh, Jonghyun; Kim, Keekyoung et al. (2014) Microfluidics-assisted fabrication of gelatin-silica core-shell microgels for injectable tissue constructs. Biomacromolecules 15:283-90
Masoumi, Nafiseh; Larson, Benjamin L; Annabi, Nasim et al. (2014) Electrospun PGS:PCL microfibers align human valvular interstitial cells and provide tunable scaffold anisotropy. Adv Healthc Mater 3:929-39
Kharaziha, Mahshid; Shin, Su Ryon; Nikkhah, Mehdi et al. (2014) Tough and flexible CNT-polymeric hybrid scaffolds for engineering cardiac constructs. Biomaterials 35:7346-54
Hsieh, Hsin-Yi; Camci-Unal, Gulden; Huang, Tsu-Wei et al. (2014) Gradient static-strain stimulation in a microfluidic chip for 3D cellular alignment. Lab Chip 14:482-93
Gaharwar, Akhilesh K; Mukundan, Shilpaa; Karaca, Elif et al. (2014) Nanoclay-enriched poly(?-caprolactone) electrospun scaffolds for osteogenic differentiation of human mesenchymal stem cells. Tissue Eng Part A 20:2088-101
Shevchenko, Yanina; Camci-Unal, Gulden; Cuttica, Davide F et al. (2014) Surface plasmon resonance fiber sensor for real-time and label-free monitoring of cellular behavior. Biosens Bioelectron 56:359-67
Hasan, Anwarul; Paul, Arghya; Vrana, Nihal E et al. (2014) Microfluidic techniques for development of 3D vascularized tissue. Biomaterials 35:7308-25
Hasan, Anwarul; Ragaert, Kim; Swieszkowski, Wojciech et al. (2014) Biomechanical properties of native and tissue engineered heart valve constructs. J Biomech 47:1949-63
Dolatshahi-Pirouz, Alireza; Nikkhah, Mehdi; Gaharwar, Akhilesh K et al. (2014) A combinatorial cell-laden gel microarray for inducing osteogenic differentiation of human mesenchymal stem cells. Sci Rep 4:3896

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