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Unformatted text preview: Dynamic reciprocity in the wound microenvironment Gregory S. Schultz, PhD 1 ; Jeffrey M. Davidson, PhD 2 ; Robert S. Kirsner, MD, PhD 3 ; Paul Bornstein, MD 4 ; Ira M. Herman, PhD 5 1. Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida, 2. Department of Pathology, Vanderbilt University Medical Center and Research Service, VA Tennessee Valley Healthcare System, Nashville, Tennessee, 3. Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, Florida, 4. Departments of Biochemistry and Medicine, University of Washington, Seattle, Washington, and 5. 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 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: 1 617 636 2991; Fax: 1 617 636 0445; Email: [email protected] Manuscript received: October 12, 2010 Accepted in final form: December 30, 2010 DOI:10.1111/j.1524-475X.2011.00673.x 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, pro- liferation, and survival during tissue development, including, e.g., embryogenesis, angiogenesis, as well as during pathologic processes including cancer, diabetes, hy- pertension, 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 at- tempt 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 thera- peutics are also brieﬂy considered. Normal wound healing is characterized by a well-coordi- nated, progressive series of events designed to restore the barrier function and mechanical integrity of the skin. Like other developmental processes and tumor growth, wound healing involves interactions between cells and their micro- environment, of which the extracellular matrix (ECM) is the primary component....
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