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(Circulation Research. 2005;97:8.)
© 2005 American Heart Association, Inc.

Review

Custom Design of the Cardiac Microenvironment With Biomaterials

Michael E. Davis, Patrick C.H. Hsieh, Alan J. Grodzinsky, Richard T. Lee

From the Cardiovascular Division (M.E.D., P.C.H.H., R.T.L.), Brigham and Women’s Hospital, Harvard Medical School, Boston; and the Division of Biological Engineering (A.J.G.), Massachusetts Institute of Technology, Cambridge.

Correspondence to Dr Richard T. Lee, Partners Research Facility, Room 279, 65 Landsdowne St, Cambridge, MA 02139 E-mail rlee{at}rics.bwh.harvard.edu

This Review is part of a thematic series on Cardiovascular Tissue Engineering, which includes the following articles:

Custom Design of the Cardiac Microenvironment With Biomaterials

Regenerative Cardiomyocytes for Cardiovascular Tissue Engineering

Engineering Myocardial Tissue

Tissue Engineering of Replacement Heart Valves

Engineering Artificial Arteries
Richard T. Lee Guest Editor

Many strategies for repairing injured myocardium are under active investigation, with some early encouraging results. These strategies include cell therapies, despite little evidence of long-term survival of exogenous cells, and gene or protein therapies, often with incomplete control of locally-delivered dose of the factor. We propose that, ultimately, successful repair and regeneration strategies will require quantitative control of the myocardial microenvironment. This precision control can be engineered through designed biomaterials that provide quantitative adhesion, growth, or migration signals. Quantitative timed release of factors can be regulated by chemical design to direct cellular differentiation pathways such as angiogenesis and vascular maturation. Smart biomaterials respond to the local environment, such as protease activity or mechanical forces, with controlled release or activation. Most of these new biomaterials provide much greater flexibility for regenerating tissues ex vivo, but emerging technologies like self-assembling nanofibers can now establish intramyocardial cellular microenvironments by injection. This may allow percutaneous cardiac regeneration and repair approaches, or injectable-tissue engineering. Finally, materials can be made to multifunction by providing sequential signals with custom design of differential release kinetics for individual factors. Thus, new rationally-designed biomaterials no longer simply coexist with tissues, but can provide precision bioactive control of the microenvironment that may be required for cardiac regeneration and repair.

Key Words: tissue engineering • biomaterials • regeneration • microenvironment

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