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CMCC 2135

Nanowired three-dimensional cardiac patches

Inventors: Daniel Kohane, Robert Langer, Tal Dvir, Brian Timko

Invention Types: Medical Device, Therapeutics

Research Areas: Regenerative Medicine, Surgery/Wound Healing

Keywords: Surgery, Tissue Engineering

For More Information Contact:  Khunkhun, Rajinder

 

Invention Description:

Engineered cardiac patches for treating damaged heart tissues after a heart attack are normally produced by seeding heart cells within three-dimensional porous biomaterial scaffolds.


These biomaterials, which are usually made of either biological polymers such as alginate or synthetic polymers such as poly(lactic acid) (PLA), help cells organize into functioning tissues, but poor conductivity of these materials limits the ability of the patch to contract strongly as a unit. Children's researchers showed that incorporating gold nanowires within alginate scaffolds can bridge the electrically resistant pore walls of alginate and improve electrical communication between adjacent cardiac cells.


The figure shows a schematic overview of three-dimensional cardiac tissue (a): Isolated cardiomyocytes are cultured in either pristine alginate or Alg-NW composites. Insets highlight the components of the engineered tissue (cardiac cells - red, alginate pore walls - blue and gold nanowires - yellow).


Whereas cardiomyocytes in pristine alginate scaffolds (b, top) typically form only small clusters that beat asynchronously and with random polarization, Alg-NW scaffolds (b, bottom) can exhibit synchronization across scaffold walls, throughout the entire scaffold.


Cardiomyocytes cultured in alginate scaffolds (c, top) form small beating clusters, but synchronously beating cardiomyocytes in Alg-NW composites (c, bottom) have the potential to form organized cardiac-like tissue. (Colors, contour lines and arrows represent the spatial and temporal evolution of the signal maximum.)


Tissues grown on these composite matrices were thicker and better aligned than those grown on pristine alginate and when electrically stimulated, the cells in these tissues contracted synchronously. Also, higher levels of the proteins involved in muscle contraction and electrical coupling are detected in the composite matrices.

Applications:

- Potential Therapeutic: tissue engineered patch for cardiac surgery, especially to assist healing after myocardial infarction|

- Research tool for a broad range of tissue s and and cell types and for drug screening

Competitive Advantages:

- It is expected that the integration of conducting nanowires within three-dimensional scaffolds may improve the therapeutic value of current cardiac patches.|

- Nanostructures incorporated into matrices foster tissue morphogenesis and functionality, improve mechanical and adhesive properties, and direct cells to self-assemble in three dimensions.|

- Key limitation of porous matrices used for cardiac tissue engineering addressed here is that their pore walls limit cell/cell interaction and delay electrical signal propagation. This developed technology has three-dimensional nanocomposites of gold nanowires within macroporous alginate scaffolds to bridge the non-conducting pore walls, increase electrical signal propagation throughout the cell seeded scaffold, and enhance the organization of functioning tissue.

Key Publications: Dvir T, Timko BP, Brigham MD, Naik SR, Karajanagi SS, Levy O, Jin H, Parker KK, Langer R, Kohane DS. Nanowired three-dimensional cardiac patches. Nat Nanotechnol. 2011 Sep 25;6(11):720-5

IPStatus: Pat. Pend.