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Basic principles of wound management

David G Armstrong, DPM, MD, PhD
Andrew J Meyr, DPM
Section Editors
Hilary Sanfey, MD
John F Eidt, MD
Joseph L Mills, Sr, MD
Eduardo Bruera, MD
Deputy Editor
Kathryn A Collins, MD, PhD, FACS


A wound is a disruption of the normal structure and function of the skin and skin architecture [1]. An acute wound has normal wound physiology and healing is anticipated to progress through the normal stages of wound healing, whereas a chronic wound is defined as one that is physiologically impaired [2,3].

To ensure proper healing, the wound bed needs to be well vascularized, free of devitalized tissue, clear of infection, and moist. Wound dressings should eliminate dead space, control exudate, prevent bacterial overgrowth, ensure proper fluid balance, be cost-efficient, and be manageable for the patient and/or nursing staff. Wounds that demonstrate progressive healing as evidenced by granulation tissue and epithelialization can undergo closure or coverage. All wounds are colonized with microbes; however, not all wounds are infected [4,5].

Many topical agents and alternative therapies are available that are meant to improve the wound healing environment and, although data are lacking to support any definitive recommendations, some may be useful under specific circumstances [6,7].

The basic principles and available options for the management of various wounds will be reviewed. The efficacy of wound management strategies for the treatment of specific wounds is discussed in individual topic reviews:

(See "Management of diabetic foot ulcers".)


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  1. Atiyeh BS, Ioannovich J, Al-Amm CA, El-Musa KA. Management of acute and chronic open wounds: the importance of moist environment in optimal wound healing. Curr Pharm Biotechnol 2002; 3:179.
  2. Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: a systematic approach to wound management. Wound Repair Regen 2003; 11 Suppl 1:S1.
  3. Golinko MS, Clark S, Rennert R, et al. Wound emergencies: the importance of assessment, documentation, and early treatment using a wound electronic medical record. Ostomy Wound Manage 2009; 55:54.
  4. Bowler PG, Duerden BI, Armstrong DG. Wound microbiology and associated approaches to wound management. Clin Microbiol Rev 2001; 14:244.
  5. Spichler A, Hurwitz BL, Armstrong DG, Lipsky BA. Microbiology of diabetic foot infections: from Louis Pasteur to 'crime scene investigation'. BMC Med 2015; 13:2.
  6. Game FL, Hinchliffe RJ, Apelqvist J, et al. A systematic review of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev 2012; 28 Suppl 1:119.
  7. Game FL, Hinchliffe RJ, Apelqvist J, et al. Specific guidelines on wound and wound-bed management 2011. Diabetes Metab Res Rev 2012; 28 Suppl 1:232.
  8. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 infectious diseases society of america clinical practice guideline for the diagnosis and treatment of diabetic foot infections. J Am Podiatr Med Assoc 2013; 103:2.
  9. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012; 54:e132.
  10. Armstrong DG, Lipsky BA. Advances in the treatment of diabetic foot infections. Diabetes Technol Ther 2004; 6:167.
  11. Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Plast Reconstr Surg 2006; 117:212S.
  12. Furnary AP, Wu Y. Clinical effects of hyperglycemia in the cardiac surgery population: the Portland Diabetic Project. Endocr Pract 2006; 12 Suppl 3:22.
  13. Armstrong DG, Lavery LA, Sariaya M, Ashry H. Leukocytosis is a poor indicator of acute osteomyelitis of the foot in diabetes mellitus. J Foot Ankle Surg 1996; 35:280.
  14. Ross R, Everett NB, Tyler R. Wound healing and collagen formation. VI. The origin of the wound fibroblast studied in parabiosis. J Cell Biol 1970; 44:645.
  15. Smith F, Dryburgh N, Donaldson J, Mitchell M. Debridement for surgical wounds. Cochrane Database Syst Rev 2013; :CD006214.
  16. Smith J. Debridement of diabetic foot ulcers. Cochrane Database Syst Rev 2002; :CD003556.
  17. Stevenson TR, Thacker JG, Rodeheaver GT, et al. Cleansing the traumatic wound by high pressure syringe irrigation. JACEP 1976; 5:17.
  18. Rodeheaver G, Pettry D, Turnbull V, et al. Identification of the wound infection-potentiating factors in soil. Am J Surg 1974; 128:8.
  19. Fernandez R, Griffiths R. Water for wound cleansing. Cochrane Database Syst Rev 2012; :CD003861.
  20. Moore ZE, Cowman S. Wound cleansing for pressure ulcers. Cochrane Database Syst Rev 2013; :CD004983.
  21. Hollander JE, Singer AJ. Laceration management. Ann Emerg Med 1999; 34:356.
  22. Moscati RM, Reardon RF, Lerner EB, Mayrose J. Wound irrigation with tap water. Acad Emerg Med 1998; 5:1076.
  23. Loeb T, Loubert G, Templier F, Pasteyer J. [Iatrogenic gas embolism following surgical lavage of a wound with hydrogen peroxide]. Ann Fr Anesth Reanim 2000; 19:108.
  24. Mote GA, Malay DS. Efficacy of power-pulsed lavage in lower extremity wound infections: a prospective observational study. J Foot Ankle Surg 2010; 49:135.
  25. Wheeler CB, Rodeheaver GT, Thacker JG, et al. Side-effects of high pressure irrigation. Surg Gynecol Obstet 1976; 143:775.
  26. Tabor OB Jr, Bosse MJ, Hudson MC, et al. Does bacteremia occur during high pressure lavage of contaminated wounds? Clin Orthop Relat Res 1998; :117.
  27. Brem H, Stojadinovic O, Diegelmann RF, et al. Molecular markers in patients with chronic wounds to guide surgical debridement. Mol Med 2007; 13:30.
  28. Armstrong DG, Lavery LA, Nixon BP, Boulton AJ. It's not what you put on, but what you take off: techniques for debriding and off-loading the diabetic foot wound. Clin Infect Dis 2004; 39 Suppl 2:S92.
  29. Cardinal M, Eisenbud DE, Armstrong DG, et al. Serial surgical debridement: a retrospective study on clinical outcomes in chronic lower extremity wounds. Wound Repair Regen 2009; 17:306.
  30. Steed DL, Donohoe D, Webster MW, Lindsley L. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic Ulcer Study Group. J Am Coll Surg 1996; 183:61.
  31. Wilcox JR, Carter MJ, Covington S. Frequency of debridements and time to heal: a retrospective cohort study of 312 744 wounds. JAMA Dermatol 2013; 149:1050.
  32. Schiffman J, Golinko MS, Yan A, et al. Operative debridement of pressure ulcers. World J Surg 2009; 33:1396.
  33. Robson MC. Treating bacterial infections in chronic wounds. Contemp Surg Suppl 2000; Sept:9.
  34. Sieggreen MY, Maklebust J. Debridement: choices and challenges. Adv Wound Care 1997; 10:32.
  35. Klasen HJ. A review on the nonoperative removal of necrotic tissue from burn wounds. Burns 2000; 26:207.
  36. O'Meara S, Al-Kurdi D, Ovington LG. Antibiotics and antiseptics for venous leg ulcers. Cochrane Database Syst Rev 2008; :CD003557.
  37. Demidova-Rice TN, Geevarghese A, Herman IM. Bioactive peptides derived from vascular endothelial cell extracellular matrices promote microvascular morphogenesis and wound healing in vitro. Wound Repair Regen 2011; 19:59.
  38. Paul AG, Ahmad NW, Lee HL, et al. Maggot debridement therapy with Lucilia cuprina: a comparison with conventional debridement in diabetic foot ulcers. Int Wound J 2009; 6:39.
  39. Andersen AS, Sandvang D, Schnorr KM, et al. A novel approach to the antimicrobial activity of maggot debridement therapy. J Antimicrob Chemother 2010; 65:1646.
  40. Nigam Y, Morgan C. Does maggot therapy promote wound healing? The clinical and cellular evidence. J Eur Acad Dermatol Venereol 2016; 30:776.
  41. Armstrong DG, Salas P, Short B, et al. Maggot therapy in "lower-extremity hospice" wound care: fewer amputations and more antibiotic-free days. J Am Podiatr Med Assoc 2005; 95:254.
  42. Sherman RA, Wyle F, Vulpe M. Maggot therapy for treating pressure ulcers in spinal cord injury patients. J Spinal Cord Med 1995; 18:71.
  43. Sherman RA. Maggot versus conservative debridement therapy for the treatment of pressure ulcers. Wound Repair Regen 2002; 10:208.
  44. Margolin L, Gialanella P. Assessment of the antimicrobial properties of maggots. Int Wound J 2010; 7:202.
  45. Opletalová K, Blaizot X, Mourgeon B, et al. Maggot therapy for wound debridement: a randomized multicenter trial. Arch Dermatol 2012; 148:432.
  46. Davies CE, Woolfrey G, Hogg N, et al. Maggots as a wound debridement agent for chronic venous leg ulcers under graduated compression bandages: A randomised controlled trial. Phlebology 2015; 30:693.
  47. Mudge E, Price P, Walkley N, Harding KG. A randomized controlled trial of larval therapy for the debridement of leg ulcers: results of a multicenter, randomized, controlled, open, observer blind, parallel group study. Wound Repair Regen 2014; 22:43.
  48. Sherman RA. Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy. Diabetes Care 2003; 26:446.
  49. Sherman RA, Shapiro CE, Yang RM. Maggot therapy for problematic wounds: uncommon and off-label applications. Adv Skin Wound Care 2007; 20:602.
  50. Steenvoorde P, Jukema GN. The antimicrobial activity of maggots: in-vivo results. J Tissue Viability 2004; 14:97.
  51. Wollina U, Liebold K, Schmidt WD, et al. Biosurgery supports granulation and debridement in chronic wounds--clinical data and remittance spectroscopy measurement. Int J Dermatol 2002; 41:635.
  52. Dumville JC, Worthy G, Soares MO, et al. VenUS II: a randomised controlled trial of larval therapy in the management of leg ulcers. Health Technol Assess 2009; 13:1.
  53. Soares MO, Iglesias CP, Bland JM, et al. Cost effectiveness analysis of larval therapy for leg ulcers. BMJ 2009; 338:b825.
  54. Wayman J, Nirojogi V, Walker A, et al. The cost effectiveness of larval therapy in venous ulcers. J Tissue Viability 2000; 10:91.
  55. Gottrup F, Jørgensen B. Maggot debridement: an alternative method for debridement. Eplasty 2011; 11:e33.
  56. Blake FA, Abromeit N, Bubenheim M, et al. The biosurgical wound debridement: experimental investigation of efficiency and practicability. Wound Repair Regen 2007; 15:756.
  57. Grassberger M, Fleischmann W. The biobag - a new device for the application of medicinal maggots. Dermatology 2002; 204:306.
  58. Steenvoorde P, Jacobi CE, Oskam J. Maggot debridement therapy: free-range or contained? An in-vivo study. Adv Skin Wound Care 2005; 18:430.
  59. Spilsbury K, Cullum N, Dumville J, et al. Exploring patient perceptions of larval therapy as a potential treatment for venous leg ulceration. Health Expect 2008; 11:148.
  60. Steenvoorde P, Budding T, Oskam J. Determining pain levels in patients treated with maggot debridement therapy. J Wound Care 2005; 14:485.
  61. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care 1998; 21:822.
  62. Fang RC, Galiano RD. A review of becaplermin gel in the treatment of diabetic neuropathic foot ulcers. Biologics 2008; 2:1.
  63. http://www.fda.gov/cder/drug/infopage/becaplermin/regranex_dhcp.pdf (Accessed on March 05, 2009).
  64. http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety-RelatedDrugLabelingChanges/ucm121631.htm (Accessed on October 10, 2011).
  65. http://www.regranex.com/ (Accessed on October 07, 2010).
  66. Falanga V, Eaglstein WH, Bucalo B, et al. Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers. J Dermatol Surg Oncol 1992; 18:604.
  67. Marques da Costa R, Jesus FM, Aniceto C, Mendes M. Double-blind randomized placebo-controlled trial of the use of granulocyte-macrophage colony-stimulating factor in chronic leg ulcers. Am J Surg 1997; 173:165.
  68. Da Costa RM, Ribeiro Jesus FM, Aniceto C, Mendes M. Randomized, double-blind, placebo-controlled, dose- ranging study of granulocyte-macrophage colony stimulating factor in patients with chronic venous leg ulcers. Wound Repair Regen 1999; 7:17.
  69. Zhang L, Chen J, Han C. A multicenter clinical trial of recombinant human GM-CSF hydrogel for the treatment of deep second-degree burns. Wound Repair Regen 2009; 17:685.
  70. Lipsky BA, Hoey C. Topical antimicrobial therapy for treating chronic wounds. Clin Infect Dis 2009; 49:1541.
  71. Storm-Versloot MN, Vos CG, Ubbink DT, Vermeulen H. Topical silver for preventing wound infection. Cochrane Database Syst Rev 2010; :CD006478.
  72. Carter MJ, Tingley-Kelley K, Warriner RA 3rd. Silver treatments and silver-impregnated dressings for the healing of leg wounds and ulcers: a systematic review and meta-analysis. J Am Acad Dermatol 2010; 63:668.
  73. Aziz Z, Abu SF, Chong NJ. A systematic review of silver-containing dressings and topical silver agents (used with dressings) for burn wounds. Burns 2012; 38:307.
  74. Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev 2007; :CD005486.
  75. Woo KY, Ayello EA, Sibbald RG. SILVER versus other antimicrobial dressings: best practices! Surg Technol Int 2008; 17:50.
  76. Kwakman PH, te Velde AA, de Boer L, et al. How honey kills bacteria. FASEB J 2010; 24:2576.
  77. http://www.dermasciences.com/medihoney-products (Accessed on April 28, 2015).
  78. Tirado DJ, Hudson NR, Maldonado CJ. Efficacy of medical grade honey against multidrug-resistant organisms of operational significance: part I. J Trauma Acute Care Surg 2014; 77:S204.
  79. Jull A, Walker N, Parag V, et al. Randomized clinical trial of honey-impregnated dressings for venous leg ulcers. Br J Surg 2008; 95:175.
  80. Subrahmanyam M. Early tangential excision and skin grafting of moderate burns is superior to honey dressing: a prospective randomised trial. Burns 1999; 25:729.
  81. Jull AB, Cullum N, Dumville JC, et al. Honey as a topical treatment for wounds. Cochrane Database Syst Rev 2015; :CD005083.
  82. Linden L, Emmans P 3rd, Safranek S. Topical preparations for wound healing. Am Fam Physician 2014; 89:978.
  83. Wijesinghe M, Weatherall M, Perrin K, Beasley R. Honey in the treatment of burns: a systematic review and meta-analysis of its efficacy. N Z Med J 2009; 122:47.
  84. Brölmann FE, Ubbink DT, Nelson EA, et al. Evidence-based decisions for local and systemic wound care. Br J Surg 2012; 99:1172.
  85. O'Meara S, Al-Kurdi D, Ologun Y, et al. Antibiotics and antiseptics for venous leg ulcers. Cochrane Database Syst Rev 2014; :CD003557.
  86. Gauglitz GG, Williams FN, Herndon DN, Jeschke MG. Burns: where are we standing with propranolol, oxandrolone, recombinant human growth hormone, and the new incretin analogs? Curr Opin Clin Nutr Metab Care 2011; 14:176.
  87. Tang JC, Dosal J, Kirsner RS. Topical timolol for a refractory wound. Dermatol Surg 2012; 38:135.
  88. Lev-Tov H, Dahle S, Moss J, Isseroff RR. Successful treatment of a chronic venous leg ulcer using a topical beta-blocker. J Am Acad Dermatol 2013; 69:e204.
  89. Braun LR, Lamel SA, Richmond NA, Kirsner RS. Topical timolol for recalcitrant wounds. JAMA Dermatol 2013; 149:1400.
  90. Brem H, Kirsner RS, Falanga V. Protocol for the successful treatment of venous ulcers. Am J Surg 2004; 188:1.
  91. Paddle-Ledinek JE, Nasa Z, Cleland HJ. Effect of different wound dressings on cell viability and proliferation. Plast Reconstr Surg 2006; 117:110S.
  92. Jeffcoate WJ, Price P, Harding KG, International Working Group on Wound Healing and Treatments for People with Diabetic Foot Ulcers. Wound healing and treatments for people with diabetic foot ulcers. Diabetes Metab Res Rev 2004; 20 Suppl 1:S78.
  93. WINTER GD. Formation of the scab and the rate of epithelization of superficial wounds in the skin of the young domestic pig. Nature 1962; 193:293.
  94. Eaglstein WH. Experiences with biosynthetic dressings. J Am Acad Dermatol 1985; 12:434.
  95. Svensjö T, Pomahac B, Yao F, et al. Accelerated healing of full-thickness skin wounds in a wet environment. Plast Reconstr Surg 2000; 106:602.
  96. Vogt PM, Andree C, Breuing K, et al. Dry, moist, and wet skin wound repair. Ann Plast Surg 1995; 34:493.
  97. Ovington LG. Hanging wet-to-dry dressings out to dry. Home Healthc Nurse 2001; 19:477.
  98. Armstrong DG, Jude EB. The role of matrix metalloproteinases in wound healing. J Am Podiatr Med Assoc 2002; 92:12.
  99. Chen WY, Rogers AA, Lydon MJ. Characterization of biologic properties of wound fluid collected during early stages of wound healing. J Invest Dermatol 1992; 99:559.
  100. Trengove NJ, Bielefeldt-Ohmann H, Stacey MC. Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen 2000; 8:13.
  101. Trengove NJ, Stacey MC, MacAuley S, et al. Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors. Wound Repair Regen 1999; 7:442.
  102. Bucalo B, Eaglstein WH, Falanga V. Inhibition of cell proliferation by chronic wound fluid. Wound Repair Regen 1993; 1:181.
  104. Dyson M, Young S, Pendle CL, et al. Comparison of the effects of moist and dry conditions on dermal repair. J Invest Dermatol 1988; 91:434.
  105. Rakel BA, Bermel MA, Abbott LI, et al. Split-thickness skin graft donor site care: a quantitative synthesis of the research. Appl Nurs Res 1998; 11:174.
  106. Thomas DR, Goode PS, LaMaster K, et al. A comparison of an opaque foam dressing versus a transparent film dressing in the management of skin tears in institutionalized subjects. Ostomy Wound Manage 1999; 45:22.
  107. Blair SD, Jarvis P, Salmon M, McCollum C. Clinical trial of calcium alginate haemostatic swabs. Br J Surg 1990; 77:568.
  108. Piacquadio D, Nelson DB. Alginates. A "new" dressing alternative. J Dermatol Surg Oncol 1992; 18:992.
  109. Lalau JD, Bresson R, Charpentier P, et al. Efficacy and tolerance of calcium alginate versus vaseline gauze dressings in the treatment of diabetic foot lesions. Diabetes Metab 2002; 28:223.
  110. Grange-Prunier A, Couilliet D, Grange F, Guillaume JC. [Allergic contact dermatitis to the Comfeel hydrocolloid dressing]. Ann Dermatol Venereol 2002; 129:725.
  111. Zhou LH, Nahm WK, Badiavas E, et al. Slow release iodine preparation and wound healing: in vitro effects consistent with lack of in vivo toxicity in human chronic wounds. Br J Dermatol 2002; 146:365.
  112. Hansson C. The effects of cadexomer iodine paste in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing. Cadexomer Iodine Study Group. Int J Dermatol 1998; 37:390.
  113. Michanek A, Hansson C, Berg G, Månesköld-Claes A. [Iodine-induced hyperthyroidism after cadexomer iodine treatment of leg ulcers]. Lakartidningen 1998; 95:5755.
  114. Coats TJ, Edwards C, Newton R, Staun E. The effect of gel burns dressings on skin temperature. Emerg Med J 2002; 19:224.
  115. Menaker GM. Wound dressings for office-based surgery. Facial Plast Surg 2004; 20:91.
  116. Achterberg V, Meyer-Ingold W. Hydroactive dressings and serum proteins: an in vitro study. J Wound Care 1996; 5:79.
  117. Charles H, Callicot C, Mathurin D, et al. Randomised, comparative study of three primary dressings for the treatment of venous ulcers. Br J Community Nurs 2002; 7:48.
  118. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999; 341:738.
  119. Ovington LG. Dressings and ajunctive therapies: AHCPR guidelines revisited. Ostomy Wound Manage 1999; 45:94S.
  120. Kimball EJ, Adams DM, Kinikini DV, et al. Delayed abdominal closure in the management of ruptured abdominal aortic aneurysm. Vascular 2009; 17:309.
  121. Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg 1997; 38:563.
  122. Joseph, E, Hamori, CA, Bergman, S, et al. A prospective randomized trial of vacuum-assisted closure versus standard therapy of chronic nonhealing wounds. Wounds 2000; 12:60.
  123. Mendez-Eastman S. Guidelines for using negative pressure wound therapy. Adv Skin Wound Care 2001; 14:314.
  124. Armstrong DG, Lavery LA, Diabetic Foot Study Consortium. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet 2005; 366:1704.
  125. Bello YM, Phillips TJ. Recent advances in wound healing. JAMA 2000; 283:716.
  126. Evans D, Land L. Topical negative pressure for treating chronic wounds. Cochrane Database Syst Rev 2001; :CD001898.
  127. Ubbink DT, Westerbos SJ, Nelson EA, Vermeulen H. A systematic review of topical negative pressure therapy for acute and chronic wounds. Br J Surg 2008; 95:685.
  128. Blume PA, Walters J, Payne W, et al. Comparison of negative pressure wound therapy using vacuum-assisted closure with advanced moist wound therapy in the treatment of diabetic foot ulcers: a multicenter randomized controlled trial. Diabetes Care 2008; 31:631.
  129. Rose JF, Giovinco N, Mills JL, et al. Split-thickness skin grafting the high-risk diabetic foot. J Vasc Surg 2014; 59:1657.
  130. Puttirutvong P. Meshed skin graft versus split thickness skin graft in diabetic ulcer coverage. J Med Assoc Thai 2004; 87:66.
  131. Blok CS, Vink L, de Boer EM, et al. Autologous skin substitute for hard-to-heal ulcers: retrospective analysis on safety, applicability, and efficacy in an outpatient and hospitalized setting. Wound Repair Regen 2013; 21:667.
  132. Sheehan P, Jones P, Giurini JM, et al. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Plast Reconstr Surg 2006; 117:239S.
  133. Bergemann R, Lauterbach KW, Vanscheidt W, et al. Economic evaluation of the treatment of chronic wounds: hydroactive wound dressings in combination with enzymatic ointment versus gauze dressings in patients with pressure ulcer and venous leg ulcer in Germany. Pharmacoeconomics 1999; 16:367.
  134. Falanga V, Margolis D, Alvarez O, et al. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Arch Dermatol 1998; 134:293.
  135. Marston WA, Hanft J, Norwood P, et al. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care 2003; 26:1701.
  136. Veves A, Falanga V, Armstrong DG, et al. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care 2001; 24:290.
  137. Edmonds M, Bates M, Doxford M, et al. New treatments in ulcer healing and wound infection. Diabetes Metab Res Rev 2000; 16 Suppl 1:S51.
  138. Barber C, Watt A, Pham C, et al. Influence of bioengineered skin substitutes on diabetic foot ulcer and venous leg ulcer outcomes. J Wound Care 2008; 17:517.
  139. Gentzkow GD, Iwasaki SD, Hershon KS, et al. Use of dermagraft, a cultured human dermis, to treat diabetic foot ulcers. Diabetes Care 1996; 19:350.
  140. Marston WA. Dermagraft, a bioengineered human dermal equivalent for the treatment of chronic nonhealing diabetic foot ulcer. Expert Rev Med Devices 2004; 1:21.
  141. Cuono C, Langdon R, McGuire J. Use of cultured epidermal autografts and dermal allografts as skin replacement after burn injury. Lancet 1986; 1:1123.
  142. Heimbach D, Luterman A, Burke J, et al. Artificial dermis for major burns. A multi-center randomized clinical trial. Ann Surg 1988; 208:313.
  143. Purdue GF. Dermagraft-TC pivotal efficacy and safety study. J Burn Care Rehabil 1997; 18:S13.
  144. Reyzelman A, Crews RT, Moore JC, et al. Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study. Int Wound J 2009; 6:196.
  145. Thom SR. Hyperbaric oxygen: its mechanisms and efficacy. Plast Reconstr Surg 2011; 127 Suppl 1:131S.
  146. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest 2007; 117:1219.
  147. Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J Med 1996; 334:1642.
  148. Wattel F, Mathieu D, Nevière R, Bocquillon N. Acute peripheral ischaemia and compartment syndromes: a role for hyperbaric oxygenation. Anaesthesia 1998; 53 Suppl 2:63.
  149. Leach RM, Rees PJ, Wilmshurst P. Hyperbaric oxygen therapy. BMJ 1998; 317:1140.
  150. Oriani G, Meazza D, Favales F, et al. Hyperbaric therapy in diabetic gangrene. J Hyperb Med 1990; 5:171.
  151. Hammarlund C, Sundberg T. Hyperbaric oxygen reduced size of chronic leg ulcers: a randomized double-blind study. Plast Reconstr Surg 1994; 93:829.
  152. Löndahl M, Katzman P, Nilsson A, et al. A prospective study: hyperbaric oxygen therapy in diabetics with chronic foot ulcers. J Wound Care 2006; 15:457.
  153. Kessler L, Bilbault P, Ortéga F, et al. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes Care 2003; 26:2378.
  154. Duzgun AP, Satir HZ, Ozozan O, et al. Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers. J Foot Ankle Surg 2008; 47:515.
  155. Abidia A, Laden G, Kuhan G, et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. Eur J Vasc Endovasc Surg 2003; 25:513.
  156. Wang C, Schwaitzberg S, Berliner E, et al. Hyperbaric oxygen for treating wounds: a systematic review of the literature. Arch Surg 2003; 138:272.
  157. Kranke P, Bennett MH, Martyn-St James M, et al. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev 2012; :CD004123.
  158. Margolis DJ, Gupta J, Hoffstad O, et al. Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: a cohort study. Diabetes Care 2013; 36:1961.
  159. Eskes A, Vermeulen H, Lucas C, Ubbink DT. Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds. Cochrane Database Syst Rev 2013; :CD008059.
  160. Bouachour G, Cronier P, Gouello JP, et al. Hyperbaric oxygen therapy in the management of crush injuries: a randomized double-blind placebo-controlled clinical trial. J Trauma 1996; 41:333.
  161. Villanueva E, Bennett MH, Wasiak J, Lehm JP. Hyperbaric oxygen therapy for thermal burns. Cochrane Database Syst Rev 2004; :CD004727.
  162. Flemming K, Cullum N. Therapeutic ultrasound for pressure sores. Cochrane Database Syst Rev 2000; :CD001275.
  163. Voigt J, Wendelken M, Driver V, Alvarez OM. Low-frequency ultrasound (20-40 kHz) as an adjunctive therapy for chronic wound healing: a systematic review of the literature and meta-analysis of eight randomized controlled trials. Int J Low Extrem Wounds 2011; 10:190.
  164. Gardner SE, Frantz RA, Schmidt FL. Effect of electrical stimulation on chronic wound healing: a meta-analysis. Wound Repair Regen 1999; 7:495.
  165. Baker LL, Chambers R, DeMuth SK, Villar F. Effects of electrical stimulation on wound healing in patients with diabetic ulcers. Diabetes Care 1997; 20:405.
  166. Peters EJ, Lavery LA, Armstrong DG, Fleischli JG. Electric stimulation as an adjunct to heal diabetic foot ulcers: a randomized clinical trial. Arch Phys Med Rehabil 2001; 82:721.
  167. Sebastian A, Syed F, Perry D, et al. Acceleration of cutaneous healing by electrical stimulation: degenerate electrical waveform down-regulates inflammation, up-regulates angiogenesis and advances remodeling in temporal punch biopsies in a human volunteer study. Wound Repair Regen 2011; 19:693.
  168. Flemming K, Cullum N. Electromagnetic therapy for the treatment of pressure sores. Cochrane Database Syst Rev 2001; :CD002930.
  169. Fulop AM, Dhimmer S, Deluca JR, et al. A meta-analysis of the efficacy of phototherapy in tissue repair. Photomed Laser Surg 2009; 27:695.
  170. Robson MC, Phillips LG, Lawrence WT, et al. The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores. Ann Surg 1992; 216:401.
  171. Robson MC, Phillips LG, Thomason A, et al. Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet 1992; 339:23.
  172. Mustoe TA, Cutler NR, Allman RM, et al. A phase II study to evaluate recombinant platelet-derived growth factor-BB in the treatment of stage 3 and 4 pressure ulcers. Arch Surg 1994; 129:213.
  173. Rees RS, Robson MC, Smiell JM, Perry BH. Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study. Wound Repair Regen 1999; 7:141.
  174. Landi F, Aloe L, Russo A, et al. Topical treatment of pressure ulcers with nerve growth factor: a randomized clinical trial. Ann Intern Med 2003; 139:635.
  175. Toon CD, Sinha S, Davidson BR, Gurusamy KS. Early versus delayed post-operative bathing or showering to prevent wound complications. Cochrane Database Syst Rev 2015; :CD010075.
  176. Hsieh PY, Chen KY, Chen HY, et al. Postoperative Showering for Clean and Clean-contaminated Wounds: A Prospective, Randomized Controlled Trial. Ann Surg 2016; 263:931.