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Tissue Eng Part A. 2018 May;24(9-10):740-751. doi: 10.1089/ten.TEA.2017.0221. Epub 2017 Nov 13.

RGDfK-Peptide Modified Alginate Scaffold for Cell Transplantation and Cardiac Neovascularization.

Author information

1
1 Department of Surgery, Columbia University Medical Center , New York, New York.
2
2 Department of Medicine, Columbia University Medical Center , New York, New York.
3
3 Department of Physiology, Maastricht University Medical Center , Maastricht, The Netherlands .
4
4 Section of Transplantation, Department of Surgery, University of Chicago , Chicago, Illinois.
5
5 Department of Cardiology and Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center , Leiden, The Netherlands .
6
6 Mesoblast Limited, Melbourne, Australia .

Abstract

Cell implantation for tissue repair is a promising new therapeutic strategy. Although direct injection of cells into tissue is appealing, cell viability and retention are not very good. Cell engraftment and survival following implantation are dependent on a sufficient supply of oxygen and nutrients through functional microcirculation as well as a suitable local microenvironment for implanted cells. In this study, we describe the development of a porous, biocompatible, three-dimensional (3D) alginate scaffold covalently modified with the synthetic cyclic RGDfK (Arg-Gly-Asp-D-Phe-Lys) peptide. Cyclic RGDfK peptide is protease resistant, highly stable in aqueous solutions, and has high affinity for cellular integrins. Cyclic RGDfK-modified alginate scaffolds were generated using a novel silicone sheet sandwich technique in combination with freeze-gelation, resulting in highly porous nonimmunogenic scaffolds that promoted both human and rodent cell survival in vitro, and neoangiogenesis in vivo. Two months following implantation in abdominal rectus muscles in rats, cyclic RGDfK-modified scaffolds were fully populated by host cells, especially microvasculature without an overt immune response or fibrosis, whereas unmodified control scaffolds did not show cell ingrowth. Importantly, modified scaffolds that were seeded with human mesenchymal precursor cells and were patched to the epicardial surface of infarcted myocardium induced myocardial neoangiogenesis and significantly improved cardiac function. In summary, purified cyclic RGDfK peptide-modified 3D alginate scaffolds are biocompatible and nonimmunogenic, enhance cell viability, promote angiogenesis, and may be used as a means to deliver cells to myocardial infarct areas to improve neovascularization and cardiac function.

KEYWORDS:

RGD peptide; alginate scaffold; angiogenesis; freeze-gelation; heart failure; mesenchymal stem cell

PMID:
28938862
PMCID:
PMC5963542
DOI:
10.1089/ten.TEA.2017.0221
[Indexed for MEDLINE]
Free PMC Article

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