Chronic Wound Healing: A Review of Current Management and Treatments

Wound healing is a complex, highly regulated process that is critical in maintaining the barrier function of skin. With numerous disease processes, the cascade of events involved in wound healing can be affected, resulting in chronic, non-healing wounds that subject the patient to significant discomfort and distress while draining the medical system of an enormous amount of resources. The healing of a superficial wound requires many factors to work in concert, and wound dressings and treatments have evolved considerably to address possible barriers to wound healing, ranging from infection to hypoxia. Even optimally, wound tissue never reaches its pre-injured strength and multiple aberrant healing states can result in chronic non-healing wounds. This article will review wound healing physiology and discuss current approaches for treating a wound.

[1]  D. Cucinotta,et al.  Raxofelast, a hydrophilic vitamin E-like antioxidant, stimulates wound healing in genetically diabetic mice. , 2001, Surgery.

[2]  T. K. Hunt,et al.  Human skin wounds: A major and snowballing threat to public health and the economy , 2009, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[3]  T. Wilgus,et al.  Regenerative healing in fetal skin: a review of the literature. , 2007, Ostomy/wound management.

[4]  J. Hanft,et al.  Healing of chronic foot ulcers in diabetic patients treated with a human fibroblast-derived dermis. , 2002, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[5]  P. Schumacker,et al.  Hypoxia-inducible factor-1 (HIF-1). , 2005, Critical care medicine.

[6]  S. Wild,et al.  Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. , 2004, Diabetes care.

[7]  H. Dillon,et al.  The natural history of streptococcal skin infection: prevention with topical antibiotics. , 1985, Journal of the American Academy of Dermatology.

[8]  K. McFarlin,et al.  Bone marrow‐derived mesenchymal stromal cells accelerate wound healing in the rat , 2006, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[9]  B H Perry,et al.  Efficacy and safety of becaplermin (recombinant human platelet‐derived growth factor‐BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[10]  S. Barnett,et al.  The effects of calcium alginate on wound healing. , 1987, Annals of the Royal College of Surgeons of England.

[11]  R. Ruberg Role of nutrition in wound healing. , 1984, The Surgical clinics of North America.

[12]  S. Zehtabchi,et al.  Silver sulfadiazine for the treatment of partial-thickness burns and venous stasis ulcers. , 2012, Journal of the American Academy of Dermatology.

[13]  K. Harding,et al.  Wound dressings , 2006, BMJ : British Medical Journal.

[14]  W. F. Todd,et al.  1995 William J. Stickel Bronze Award. Prevalence of mixed infections in the diabetic pedal wound. A retrospective review of 112 infections. , 1995, Journal of the American Podiatric Medical Association.

[15]  Benjamin A Lipsky,et al.  Topical antimicrobial therapy for treating chronic wounds. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  D G Smith,et al.  Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. , 1999, Diabetes care.

[17]  L. Norgren,et al.  A randomized trial comparing cadexomer iodine and standard treatment in the out‐patient management of chronic venous ulcers , 1983, The British journal of dermatology.

[18]  M. Stacey,et al.  Qualitative bacteriology and leg ulcer healing. , 1996, Journal of wound care.

[19]  A. Andrews,et al.  Maggots are useful in treating infected or necrotic wounds , 1999, BMJ.

[20]  G. Lazarus,et al.  Treating the chronic wound: A practical approach to the care of nonhealing wounds and wound care dressings. , 2008, Journal of the American Academy of Dermatology.

[21]  Rachel Smith,et al.  Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers , 2002, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[22]  M. Klein,et al.  Acute management of facial burns. , 2009, Clinics in plastic surgery.

[23]  Marjana Tomic-Canic,et al.  Cellular and molecular basis of wound healing in diabetes. , 2007, The Journal of clinical investigation.

[24]  J. Risteli,et al.  Synthesis of type I collagen in healing wounds in humans. , 1991, Annals of surgery.

[25]  K M Sedlarik,et al.  [Wound dressings]. , 1994, Medizinische Monatsschrift fur Pharmazeuten.

[26]  S. Davis,et al.  Use of topical antibiotics as prophylaxis in clean dermatologic procedures. , 2012, Journal of the American Academy of Dermatology.

[27]  S. Percival,et al.  A prospective randomised open label study to evaluate the potential of a new silver alginate/carboxymethylcellulose antimicrobial wound dressing to promote wound healing , 2010, International wound journal.

[28]  V. Falanga,et al.  Treatment of chronic wounds with bone marrow-derived cells. , 2003, Archives of dermatology.

[29]  R. Tuan,et al.  Mesenchymal stem cell therapy for attenuation of scar formation during wound healing , 2012, Stem Cell Research & Therapy.

[30]  P. Kranke,et al.  Hyperbaric oxygen therapy for chronic wounds. , 2004, The Cochrane database of systematic reviews.

[31]  J. Q. Rosso,et al.  A comparison of postprocedural wound care treatments: Do antibiotic-based ointments improve outcomes? , 2012 .

[32]  G R Tobin,et al.  Physiology and healing dynamics of chronic cutaneous wounds. , 1998, American journal of surgery.

[33]  T. K. Hunt,et al.  Inhibitory Effects of Vitamin E on Collagen Synthesis and Wound Repair , 1972, Annals of surgery.

[34]  S. Benrimoj,et al.  Topical Antimicrobial Prophylaxis in Minor Wounds , 1997, The Annals of pharmacotherapy.

[35]  G. Leese,et al.  Blood flow changes in diabetic foot ulcers treated with dermal replacement therapy. , 2002, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[36]  Susan C. Taylor,et al.  Postprocedural wound-healing efficacy following removal of dermatosis papulosa nigra lesions in an African American population: a comparison of a skin protectant ointment and a topical antibiotic. , 2011, Journal of the American Academy of Dermatology.

[37]  W. Obremskey,et al.  Use of Negative‐pressure Wound Therapy in Orthopaedic Trauma , 2012, The Journal of the American Academy of Orthopaedic Surgeons.

[38]  Y. Eliezri,et al.  Prospective study of wound infections in Mohs micrographic surgery using clean surgical technique in the absence of prophylactic antibiotics. , 2010, Journal of the American Academy of Dermatology.

[39]  H. Sorg,et al.  Wound Repair and Regeneration , 2012, European Surgical Research.

[40]  G. Mulder,et al.  FIBRIN CUFF LYSIS IN CHRONIC VENOUS ULCERS TREATED WITH A HYDROCOLLOID DRESSING , 1993, International journal of dermatology.

[41]  Jacob R. Goheen,et al.  Skin shedding and tissue regeneration in African spiny mice (Acomys) , 2012, Nature.

[42]  G. Evans,et al.  Advances in Wound Healing: A Review of Current Wound Healing Products , 2012, Plastic surgery international.

[43]  S. Percival,et al.  Assessing the effect of an antimicrobial wound dressing on biofilms , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[44]  M. Longaker,et al.  Scarless fetal skin wound healing update. , 2012, Birth defects research. Part C, Embryo today : reviews.

[45]  M. Schneider,et al.  Quantitative assessment of bacterial invasion of chronic ulcers. Statistical analysis. , 1983, American journal of surgery.

[46]  M. Löndahl,et al.  Hyperbaric Oxygen Therapy Facilitates Healing of Chronic Foot Ulcers in Patients With Diabetes , 2010, Diabetes Care.

[47]  R. Burrell,et al.  Infection and the chronic wound: a focus on silver. , 2005, Advances in skin & wound care.

[48]  Katherine E. Degen,et al.  Embryonic wound healing: a primer for engineering novel therapies for tissue repair. , 2012, Birth defects research. Part C, Embryo today : reviews.

[49]  Stephanie Wu,et al.  Wound care: the role of advanced wound-healing technologies. , 2010, Journal of the American Podiatric Medical Association.

[50]  B. Crawley,et al.  The Importance of Dietary Protein in Healing Pressure Ulcers , 1993, Journal of the American Geriatrics Society.

[51]  W. Rogowski,et al.  Systematic review of economic evaluations of human cell-derived wound care products for the treatment of venous leg and diabetic foot ulcers , 2009, BMC health services research.

[52]  R. Weller,et al.  Topically applied nitric oxide induces T-lymphocyte infiltration in human skin, but minimal inflammation. , 2008, The Journal of investigative dermatology.

[53]  S. Moberg,et al.  A Randomized Trial of Cadexomer Iodine in Decubitus Ulcers , 1983, Journal of the American Geriatrics Society.

[54]  D. Margolis,et al.  Hemoglobin A1c is a Predictor of Healing Rate In Diabetic Wounds , 2011, The Journal of investigative dermatology.

[55]  M. Peppa,et al.  Advanced glycoxidation products and impaired diabetic wound healing , 2009, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[56]  P. Chambon,et al.  Insulin-like growth factor-1 promotes wound healing in estrogen-deprived mice: new insights into cutaneous IGF-1R/ERα cross talk. , 2012, The Journal of investigative dermatology.

[57]  T. K. Hunt,et al.  Wound healing and wound infection. What surgeons and anesthesiologists can do. , 1997, The Surgical clinics of North America.

[58]  Thomas K. Hunt,et al.  Problem Wounds: The Role of Oxygen , 1989 .

[59]  Olivera Stojadinovic,et al.  PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[60]  J. Friedman,et al.  Nitric oxide-releasing nanoparticles accelerate wound healing by promoting fibroblast migration and collagen deposition. , 2012, The American journal of pathology.

[61]  Olivera Stojadinovic,et al.  Molecular Markers in Patients with Chronic Wounds to Guide Surgical Debridement , 2007, Molecular medicine.

[62]  K. Chung,et al.  A clinical trial of Integra Template for diabetic foot ulcer treatment , 2015, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[63]  J. Carvalheira,et al.  Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial , 2012, PloS one.

[64]  Thomas A. Mustoe, MD, FACS,et al.  Transforming growth factor-beta1 fails to stimulate wound healing and impairs its signal transduction in an aged ischemic ulcer model: importance of oxygen and age. , 1999, The American journal of pathology.

[65]  Alan L Miller,et al.  Nutritional support for wound healing. , 2003, Alternative medicine review : a journal of clinical therapeutic.

[66]  W. Marston,et al.  The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. , 2003, Diabetes care.

[67]  H Peter Lorenz,et al.  Scarless fetal wound healing: a basic science review. , 2010, Plastic and reconstructive surgery.

[68]  D. Margolis,et al.  Hemoglobin A 1 c Predicts Healing Rate in Diabetic Wounds , 2011 .

[69]  P. Prete,et al.  Growth effects of Phaenicia sericata larval extracts on fibroblasts: mechanism for wound healing by maggot therapy. , 1997, Life sciences.

[70]  Luke Barron,et al.  Macrophages: Master Regulators of Inflammation and Fibrosis , 2010, Seminars in liver disease.

[71]  J. Dover,et al.  Leg ulcers. , 1991, Journal of the American Academy of Dermatology.

[72]  E. Seifter,et al.  Zone II flexor tendon repair: Effects of vitamins A, E, β-carotene , 1990 .