Dynamic reciprocity in the wound microenvironment

Authors

  • Gregory S. Schultz PhD,

    1. Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida,
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  • Jeffrey M. Davidson PhD,

    1. Department of Pathology, Vanderbilt University Medical Center and Research Service, VA Tennessee Valley Healthcare System, Nashville, Tennessee,
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  • Robert S. Kirsner MD, PhD,

    1. Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, Florida,
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  • Paul Bornstein MD,

    1. Departments of Biochemistry and Medicine, University of Washington, Seattle, Washington,
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  • Ira M. Herman PhD

    1. Program in Cellular and Molecular Physiology, Department of Molecular Physiology and Pharmacology, Center for Innovations in Wound Healing Research, Tufts University School of Medicine, Boston, Massachusetts
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Reprint requests:
Ira M. Herman, Program in Cellular and Molecular Physiology, Department of Molecular Physiology and Pharmacology, Center for Innovations in Wound Healing Research, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111.
Tel: +617 636 2991;
Fax: +617 636 0445;
Email: ira.herman@tufts.edu

ABSTRACT

Here, we define dynamic reciprocity (DR) as an ongoing, bidirectional interaction among cells and their surrounding microenvironment. In this review, we posit that DR is especially meaningful during wound healing as the DR-driven biochemical, biophysical, and cellular responses to injury play pivotal roles in regulating tissue regenerative responses. Such cell–extracellular matrix interactions not only guide and regulate cellular morphology, but also cellular differentiation, migration, proliferation, and survival during tissue development, including, e.g., embryogenesis, angiogenesis, as well as during pathologic processes including cancer, diabetes, hypertension, and chronic wound healing. Herein, we examine DR within the wound microenvironment while considering specific examples across acute and chronic wound healing. This review also considers how a number of hypotheses that attempt to explain chronic wound pathophysiology may be understood within the DR framework. The implications of applying the principles of DR to optimize wound care practice and future development of innovative wound healing therapeutics are also briefly considered.

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