Chronic wound repair and healing in older adults: current status and future research

Abstract

Older adults are more likely to have chronic wounds than younger people, and the effect of chronic wounds on quality of life is particularly profound in this population. Wound healing slows with age, but the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The effect of age and accompanying multimorbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables; lack of standardization in data collection; and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this article, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify research questions to guide future study of age-associated changes in chronic wound healing.

Keywords: chronic wound; diabetic foot ulcer; pressure ulcer; venous leg ulcer; wound healing; wound repair.

Conflict of interest statement

Conflict of Interest: Dr. Gould reports nonfinancial support from MiMedx, Cytomedix, Celleration, and Cardinal Health. Dr. Abadir has a patent pending on a novel, protective, anti-inflammatory receptor and its use in preservation of mitochondrial function, wound healing and repair. Dr. Davidson reports grants from NIH and the Department of Veterans Affairs. Dr. Fife is the Executive Director of The Chronic Disease Registry (d/b/a the U.S. Wound Registry), a 501c(3) organization that provided some of the data for this presentation, specifically the data on the use of biological dressings in older adults and their associated healing rates. Dr. Grice reports grants from Janssen Research and Development and consulting fees from GOJO, Amway International, GlaxoSmithKline, and L’Oreal. Dr. High reports grants from Chimerix, Sanofi-Pasteur, Optimer, Astellas; is a consultant for University of Virginia and the University of Minnesota; and has received other financial or material support from McGraw-Hill Publishers and Uptodate, Inc. Dr. Jacobson is an employee of Smith & Nephew, which produces the cell therapy product described in the presentation. Dr. McFarland Horne reports grants from John A. Hartford Foundation during the conduct of the study. Dr. Tomic-Canic reports grants from NIH, Organogenesis Inc., Novan, and Smith & Nephew; is a scientific board member for Molnlycke; and has the following patents: Methods and compositions for promoting wound healing issued to Hospital for Special Surgery; GM-CSF cosmeceutical compositions and methods of use thereof issued to NYU School of Medicine; Biological markers of chronic wound tissue and methods of using for criteria in surgical debridement pending to NYU School of Medicine; De novo synthesis of glucocortocoid in the epidermis and it uses and applications patent pending to NYU School of Medicine; and growth factor-mediated cosmeceuticals and use of thereof to enhances skin quality patent pending to NYU School of Medicine.

© 2015 by the American Geriatrics Society and the Wound Healing Society.

Figures

Figure 1

Burn wound repair is delayed in aged mice. (A) Wound area was evaluated 0, 3, 7, 14, and 21 days after burn injury in 2-month-old (young) versus 2-year-old C57BL/6J mice. *P < .05 versus young mice. (B) Bone marrow–derived angiogenic cells were identified using fluorescence-activated cell sorting as CXCR4+/Sca-1+. (C) Human inducibility factor (HIF)-1a concentrations in response to burn injury are lower in aged than younger mice. (D) Bone marrow–derived angiogenic cells from young male mice (Y) administered through tail vein injection to recipient female mice with burn wounds were less able to home in older recipients (O) than in younger ones (Y). Donor cells were identified using the Sry gene as a marker. *P < .01 versus young recipients. N = normal; B = burned. Adapted from Zhang X et al.

Figure 2

Implications of age-associated inflammation for infection. In a mouse model, older mice inoculated with Staphylococcus aureus fail to clear infection, unlike younger mice. *P < .001 versus young at same time point using two-way analysis of variance. Source: Brubaker et al.