A Method for Tissue-Engineering Organ Building Blocks



Researchers from MUSC and University of South Carolina have developed a new method for generating tissue-engineered rings (toroids) of aligned contractile cells. The novel approach provides self-organized morphogenetic principles that may be used as a 3D blood vessel construction or wound healing enhancer (figure 1). 


Figure 1. Hypothetical approaches of how contractile toroids could be used (A) to be assembled iteratively into the branched tubular scaffold of an artificial blood vessel or (B) to enhance wound closure.



The complex shapes, surfaces and internal structures of body organs, including blood vessels, are one of the most challenges to overcome in the field of tissue engineering. Moreover, the component tissues of organs possess dynamic contractile and mechanically responsive elements such as sphincter muscles. The ability to accurately recapitulate naturally occurring complexities of shape, internal structure, and biomechanical functionality is a key goal of tissue engineering. The epithelial-mesenchymal transition (EMT) precedes virtually every cellular differentiation in the embryo.



The present invention describes a unique and non-obvious series of steps to stimulate an EMT-like state in cells in a culture dish (referred to as EMT-priming or activation) (figure 2).


Figure 2. Rat epicardial (REC) cells (A–D) and human bone marrow stem (BMS) cells (E–H) migrate to form toroidal rings when layered onto polymerized collagen and allowed to progress through an EMT (A, C, E, G), but remain relatively uniformly dispersed within the matrix when mixed into the gels before polymerization (B, D, F, H).




• Microstructure and function closely resemble naturally occurring complexities of contractile tissues in living organisms, including humans.

• Method can be adjusted to generate other useful objects, including spheroids.

• Utility has been demonstrated: inventors have successfully grafted the toroids (subject invention) with adult stem cells into skin wounds and observed the toroids accelerated wound closure, reduced scar tissue and enhanced the regenerative effects of wound healing drug TGF-B3.


Key Words: tissue engineering, wound healing, toroid, adult stem cells, self-organizing, tissue regeneration



Robert G. Gourdie et al., “Self-Organizing Tissue-Engineered Constructs in Collagen Hydrogels” Microsc. Microanal. 18, 99–106, 2012


Inventors: Robert G. Gourdie       

Patent Status8,409,603, 8,815,556

MUSC-FRD Technology ID: P0847



Patent Information:
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Robert Gourdie
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