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Front Bioeng Biotechnol. 2015 Apr 1;3:45. doi: 10.3389/fbioe.2015.00045. eCollection 2015.

Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine.

Author information

1
Host Defense, Immunology Frontier Research Center, Osaka University , Osaka , Japan.
2
Cell and Gene Therapy, Department of Biomedicine, Basel University , Basel , Switzerland ; Department of Surgery, Basel University Hospital , Basel , Switzerland.
3
Cell and Gene Therapy, Department of Biomedicine, Basel University , Basel , Switzerland ; Department of Surgery, Basel University Hospital , Basel , Switzerland ; Plastic, Reconstructive, Aesthetic and Hand Surgery, Department of Surgery, Basel University Hospital , Basel , Switzerland.
4
Plastic, Reconstructive, Aesthetic and Hand Surgery, Department of Surgery, Basel University Hospital , Basel , Switzerland.
5
Cell and Gene Therapy, Department of Biomedicine, Basel University , Basel , Switzerland ; Department of Surgery, Basel University Hospital , Basel , Switzerland ; Vascular Surgery, Department of Surgery, Basel University Hospital , Basel , Switzerland.
6
Vascular Surgery, Department of Surgery, Basel University Hospital , Basel , Switzerland.
7
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL) , Lausanne , Switzerland.
8
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL) , Lausanne , Switzerland ; Institute for Molecular Engineering, University of Chicago , Chicago, IL , USA ; Argonne National Laboratory, Materials Science Division , Argonne, IL , USA.

Abstract

Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localization of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.

KEYWORDS:

angiogenesis; extracellular matrix; fibrin; growth factors; protein engineering

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