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

Abstract

The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound healing slows with age. However, 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 impact of age and accompanying multi-morbidity 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 paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age-associated changes in chronic wound healing.

Conflict of interest statement

Conflicts of interest were acknowledged as follows:

Dr. Gould reports non-financial support from MiMedx, Cytomedix, Celleration, and Cardinal Health.

Dr. Abadir has a patent Novel, protective, anti-inflammatory receptor and its use in preservation of mitochondrial function, wound healing and repair pending.

Dr. Davidson reports grants from National Institutes of Health 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, USWR), a 501C(3) organization which provided some of the data for this presentation, specifically the data on the use of biological dressings among older patients and their associated healing rates.

Dr. Grice reports grants from Janssen Research and Development; personal 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, other financial or material support from McGraw-Hill Publishers and Uptodate, Inc.

Dr. Jacobson is a Smith and Nephew employee 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. In addition, Dr. Tomic-Canic has the following patents: Methods and compositions for promoting wound healing issued to Hospital for Special Surgery; GM-CSF ceosmeceutical 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; Denovo 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.

H.Brem, M.Carter, T. Conner-Kerr, L.DiPietro, V.Falanga, S.Gardner, J.Harmon, W. Hazzard, P.Houghton, R. Kirsner, E.Kovacs, D.Margolis, M.Reed, K.Schmader, D.Sullivan, S.Thom, J.Walston, J.Whitney, J.Williams, S.Zieman: No conflicts to disclose

© 2014 by 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 following burn injury in 2 month old (young) vs 2 year old C57BL/6J mice. B. Bone marrow-derived angiogenic cells were identified by FACS as CXCR4+/Sca-1+. C. HIF1 concentrations in response to burn injury are reduced in aged mice, compared with younger ones. D. Bone marrow-derived angiogenic cells transferred from young male mice show impaired homing in older recipient mice, compared with younger ones. Donor cells were identified using the Sry gene as a marker. N, normal; B, burned. Adapted from: Zhang X et al. Aging impairs the mobilization and homing of bone marrow-derived angiogenic cells to burn wounds. J Mol Med. 2011;89(10):985-95.

Figure 2

Implications of age-associated inflammation for infection. In a mouse model, older mice inoculated with Staphylococcus aureus fail to clear infection, compared with younger mice. Source: Brubaker AL, Rendon JL, Ramirez L, Choudhry MA, Kovacs EJ. Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age. Journal of immunology 2013;190(4):1746-57. Copyright 2013. The American Association of Immunologists, Inc.