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(Circulation. 2005;111:442-450.)
© 2005 American Heart Association, Inc.

Molecular Cardiology

Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells

Michael E. Davis, PhD; J.P. Michael Motion, BS; Daria A. Narmoneva, PhD; Tomosaburo Takahashi, MD, PhD; Daihiko Hakuno, MD, PhD; Roger D. Kamm, PhD; Shuguang Zhang, PhD; Richard T. Lee, MD

From the Cardiovascular Division (M.E.D., J.P.M.M., D.A.N., T.T., D.H., R.T.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, and the Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge (D.A.N., R.D.K., S.Z., R.T.L.), Mass.

Correspondence to Richard T. Lee, MD, Partners Research Facility Room 280, 65 Landsdowne St, Cambridge, MA 02139.

Received July 15, 2004; revision received September 20, 2004; accepted October 18, 2004.

Background— Promoting survival of transplanted cells or endogenous precursors is an important goal. We hypothesized that a novel approach to promote vascularization would be to create injectable microenvironments within the myocardium that recruit endothelial cells and promote their survival and organization.

Methods and Results— In this study we demonstrate that self-assembling peptides can be injected and that the resulting nanofiber microenvironments are readily detectable within the myocardium. Furthermore, the self-assembling peptide nanofiber microenvironments recruit progenitor cells that express endothelial markers, as determined by staining with isolectin and for the endothelial-specific protein platelet–endothelial cell adhesion molecule-1. Vascular smooth muscle cells are recruited to the microenvironment and appear to form functional vascular structures. After the endothelial cell population, cells that express -sarcomeric actin and the transcription factor Nkx2.5 infiltrate the peptide microenvironment. When exogenous donor green fluorescent protein–positive neonatal cardiomyocytes were injected with the self-assembling peptides, transplanted cardiomyocytes in the peptide microenvironment survived and also augmented endogenous cell recruitment.

Conclusions— These experiments demonstrate that self-assembling peptides can create nanofiber microenvironments in the myocardium and that these microenvironments promote vascular cell recruitment. Because these peptide nanofibers may be modified in a variety of ways, this approach may enable injectable tissue regeneration strategies.

Key Words: tissue engineering • microenvironment • regeneration

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