Research Area:
Cardiac Tissue Engineering

Robert G. Dennis, Ph.D.
Bob's Home Page   Current ResearchMuscle Mechanics Lab (U of M)     Biomechatronics Group @ MIT

Objective:  To engineer functional mammalian cardiac muscle constructs in vitro.

[view movie of spontaneously contracting engineered cardiac muscle]
[view movie of self-organizing engineered cardiac muscle in culture]

Rationale:
    The potential applications for functional engineered cardiac muscle extend from basic research to drug discovery to, and eventually to engineered heart tissues for surgical transplantation.  My current engineered cardiac muscle constructs are being used for basic research in tissue self-organization, and cardiac tissue development.

Background:
    To the best of my knowledge, there has been little or no success in the engineering of functional cardiac muscle in vitro.  Investigators have explanted slices of ventricle wall or papillary muscles, but these surgically-removed tissue specimens only retain their contractility for a short period (a few hours at most) before losing function.  Currently, my tissue-engineered cardiac muscles retain contractility in culture for several weeks, during which time they self-organize (no artificial scaffolds are required for the contractile region of the specimen), spontaneously contract at a frequency of approximately 1 Hz, and retain their electrical excitability.

Experimental Approach:
Our work in this area is still very preliminary, and I am seeking funding for additional research.  Video clips of the self organizing cardiac tissue are provided below.

 

The image to the left is a still frame from a video of a monolayer of cardiac myocytes, self-organizing into a culindrical tissue structure in culture (video taped on January 1, 2002).  The monolayer of cells is actually composed of both primary mammalian cardiac myocytes and fibroblasts.  Note that as the monolayer contracts spontaneously (in real time), the cell monolayer peels away from the substrate material (top of frame) a small amount with each contraction.  Under the correct culture conditions, the self-organization of the cardiac tissue is visible with the naked eye (no magnification is required)

The square grid pattern is 1mm x 1mm in size, the smaller squares being 100 microns on each edge.

To see the full length video, click this link (~17MB)
To see a shorter version, click the image or this link (~4MB)

(Photograph and video by R.G. Dennis 1/1/2002)

 


 
The image to the left is a still frame from a video of a randomly-organized cardiac muscle tissue mass.  Without anchor points to define the long axis of the self-organizing tissue mass, the cardiac tissue will self-organize into a random web of spontaneously contracting tissue.

The square grid pattern is 1mm x 1mm in size, the smaller squares being 100 microns on each edge.

To see the full length video, click this link (~2.9MB)
 
 

(Photograph and video by R.G. Dennis 1/1/2002)




Investigators:
Several people in the laboratory are actively working on this research:
    Bob Dennis - Professor, Biomedical and Mechanical Engineering
    Lisa Larkin - Research Scientist, Internal Medicine & Institute of Gerontology
    Ellen Arruda - Professor, Mechanical Engineering
    Marvin Boluyt - Professor, Kinesiology
    Ravi Birla - Graduate Student, Biomedical Engineering
    Yen Chih Huang - Graduate Student, Biomedical Engineering

Current and Future research:
    My future research will be directed toward integrating nerve and muscle tissue in vitro to increase the excitability of the tissue and enhance the expression of adult phenotypes, the application of mechanical and electrical interventions to promote growth and development of the tissue, improved mechanical interface between the muscle and its attachment points using tissue engineered tendons, and ultimately the addition of a vascular system with self-organizing vascular endothelium.

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