Tissue engineering holds great promise for enabling alternative therapies for diseases such as diabetes, heart and liver failure. A common approach in tissue engineering is seeding cells in biodegradable scaffolds, which brings cells together in close proximity, aiming to mimic the native tissue environment. These scaffolds are expected to degrade and replaced by cellular growth and extracellular matrix deposition to generate a natural tissue. However, challenges remain with the current approaches, such as: 1) The inability to achieve a complex three- dimensional (3D) cellular architecture and organization (i.e. cardiac tissue is made of three major type of cells;i) cardiomyocytes ii) cardiofibroblasts, and iii) endothelial cells;2) The limited control over cell-cell proximity with microscale resolution;3) The inability to generate micro-engineered tissue constructs at high throughput with uniform cell distribution and high cell seeding density;4) The lack of vascularity which results in cell necrosis and loss of function limiting the biologically relevant engineered tissues (i.e. diffusion length of metabolites is, typically, smaller than 300 micron). We hypothesized that engineered nanofilms can be used to assemble microgels into 3D constructs which can be integrated in a fluidic device to increase assembly throughput. The goal of this project is to address these challenges by developing a Microscale Acoustic System of Nanocoatings (MASON). In this proposal, we will merge directional nanocoating (i.e. ratchets) for transport of microgels, acoustic micro electro- mechanical systems (MEMS), and microscale hydrogel (microgel) fabrication technologies to achieve microgel assembly with controlled cellular architecture. We propose to build complex structures of biodegradable microgels in a microfluidic device based on directed assembly. Thus, the proposed novel microgel assembly approach presents a promising direction towards synthetic tissue engineering which is applicable to multiple organ systems. We expect to show that this novel approach will be significantly more efficient in addressing the problems outlined above than existing microgel assembly technologies.

Public Health Relevance

The final outcome of the project will offer a broadly applicable, scalable and easy-to-use microscale assembly on a versatile microfluidic platform that has impact in tissue engineering. The platform will enable sophisticated tools and methods to create 3D tissue models that will target tissue/organ regeneration as well as pharmaceutical research and drug discovery studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL112114-01
Application #
8228606
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Lundberg, Martha
Project Start
2012-01-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
1
Fiscal Year
2012
Total Cost
$250,479
Indirect Cost
$61,250
Name
Pennsylvania State University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
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Bouyer, Charlène; Chen, Pu; Güven, Sinan et al. (2016) A Bio-Acoustic Levitational (BAL) Assembly Method for Engineering of Multilayered, 3D Brain-Like Constructs, Using Human Embryonic Stem Cell Derived Neuro-Progenitors. Adv Mater 28:161-7
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Baday, Murat; Calamak, Semih; Durmus, Naside Gozde et al. (2016) Integrating Cell Phone Imaging with Magnetic Levitation (i-LEV) for Label-Free Blood Analysis at the Point-of-Living. Small 12:1222-9
Chen, Pu; Güven, Sinan; Usta, Osman Berk et al. (2015) Biotunable acoustic node assembly of organoids. Adv Healthc Mater 4:1937-43
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Tasoglu, Savas; Khoory, Joseph A; Tekin, Huseyin C et al. (2015) Levitational Image Cytometry with Temporal Resolution. Adv Mater 27:3901-8
Tasoglu, Savas; Yu, Chu Hsiang; Liaudanskaya, Volha et al. (2015) Magnetic Levitational Assembly for Living Material Fabrication. Adv Healthc Mater 4:1469-76, 1422
Chen, Pu; Luo, Zhengyuan; Güven, Sinan et al. (2014) Microscale assembly directed by liquid-based template. Adv Mater 26:5936-41
Tasoglu, S; Diller, E; Guven, S et al. (2014) Untethered micro-robotic coding of three-dimensional material composition. Nat Commun 5:3124

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