Using a diagnostic tool to identify elevated protease activity levels in chronic and stalled wounds: A consensus panel discussion

Ostomy Wound Management

Volumn 57, Issue 12, 2011, Pages 36-46

  Snyder, Robert J ^a,b,c   Driver, Vickie ^d,e   Fife, Caroline E ^f,g   Lantis, John ^h   Peirce, Benjamin ⁱ   Serena, Thomas ^j   Weir, Dot ^k  

^a Systagenix Wound Care   (United States)

^b BARRY UNIVERSITY   (United States)

^c TEMPLE UNIVERSITY SCHOOL OF PODIATRIC MEDICINE   (United States)

^d BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e Limb Preservation and Wound Healing   (United States)

^f UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^g INTELLICURE INC   (United States)

^h Och Spine at New York Presbyterian Hospitals   (United States)

ⁱ Gentiva Health Services   (United States)

^j Penn North Centers for Advanced Wound Care   (United States)

^k Wound Care Osceola Regional Medical Center   (United States)

more..

Author keywords

chronic wounds; consensus; metalloproteases; proteases; wound healing trajectory

Indexed keywords

PEPTIDE HYDROLASE;

CHRONIC DISEASE; CONSENSUS DEVELOPMENT; ENZYMOLOGY; HUMAN; INJURY; METABOLISM; REVIEW; WOUND HEALING;

CHRONIC DISEASE; HUMANS; PEPTIDE HYDROLASES; WOUND HEALING; WOUNDS AND INJURIES;

EID: 84865803236     PISSN: 08895899     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (124)

1. Singer AJ, Clark RA. Cutaneous wound healing. New Engl J Med. 1999;341(10):738-746.
2. Falanga V, Grinnell F, Gilchrest B, Maddox YT, Moshell A. Workshop on the pathogenesis of chronic wounds. J Invest Dermatol. 1994;102(1):125-127.
3. Lazarus GS, Cooper DM, Knighton DR, et al. Defnitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol. 1994;130(4):489-493.
4. Snyder R, Cullen B. Point of care diagnostic tests in wound management: targeted therapy for excessive protease activity-the frst frontier. Wound Care Hyperb Med. 2011;2(3):54-61.
5. Peppa M, Stavroulakis P, Raptis SA. Advanced glycoxidation products and impaired diabetic wound healing. Wound Repair Regen. 2009;17(4):461-472.
6. Wicke C, Halliday B, Allen D, et al. Efects of steroids and retinoids on wound healing. Arch Surg. 2000;135(11):1265-1270.
7. Dostal GH, Gamelli RL. The diferential efect of corticosteroids on wound disruption strength in mice. Arch Surg. 1990;125(5):636-640.
8. Kelley S F, Felix AM, Ehrlich H P. The antagonism of glucocorticoid inhibition of wound healing in rats by growth hormone-releasing factor. Proc Soc Exp Biol Med. 1990;194(4):320-326.
9. Hunt TK, Ehrlich H P, Garcia JA, Durphy JE. Efect of vitamin A on reversing the inhibitory efect of corticosterone on healing of open wounds in animals and men. Ann Surg. 1969;170:633-641.
10. Lévy JJ, von Rosen J, Gassmüller J, Kleine Kuhlmann R, Lange L. Validation of an in vivo wound healing model for the quantifcation of pharmacological efects on epidermal regeneration. Dermatology. 1995;190(2):136-141.
11. International consensus. The role of proteases in wound diagnostics. An expert working group review. London: Wounds International; 2011. Available at: www.woundsinternational.com/article.php?contentid-127&articleid-9869. Accessed October 31, 2011.
12. World Union of Wound Healing Societies (WUWHS). Principles of Best Practice: Diagnostics and Wounds. A Consensus Document. London: MEP Ltd; 2008.
13. Schraibman IG. The signifcance of beta-haemolytic streptococci in chronic leg ulcers. Ann R Coll Surg Engl. 1990;72(2):123-124.
14. Bornstein P, McPherson J, Sage H. Synthesis and excretion of structural macromolecules by endothelial cells in culture. In: Nossel HL, Vogel HJ (eds). Pathobiology of the Endothelial Cell. New York, NY: Academic Press;1982:215-228.
15. Rivera J, Lozano ML, Navarro-Nunez L, Vicente V. Platelet receptors and signaling in the dynamics of thrombus formation. Haematologica. 2009;94(5):700-711.
16. Schultz GS, Davidson JM, Kirsner RS, Bornstein P, Herman IM. Dynamic reciprocity in the wound microenvironment. Wound Repair Regen. 2011;19(2):134-148.
17. Clark RA. Fibrin is a many splendored thing. J Invest Dermatol. 2003;121(5):xxi-xxii.
18. Shaw RJ, Doherty DE, Ritter AG, Benedict SH, Clark RA. Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos, c-jun, and EGR2 mRNA. J Cell Biol. 1990; 111(5 Pt 1):2139-2148.
19. Haskill S, Johnson C, Eierman D, Becker S, Warren K. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 1988;140(5):1690-1694.
20. Chen P, Parks WC. Role of matrix metalloproteinases in epithelial migration. J Cell Biochem. 2009;108(6):1233-1243.
21. Hafner J, Schaad I, Schneider E, Seifert B, Burg G, Cassina PC. Leg ulcers in peripheral arterial disease (arterial leg ulcers): impaired wound healing above the threshold of chronic critical limb ischemia. J Am Acad Dermatol. 2000;43(6):1001-1008.
22. Wassermann E, van Griensven M, Gstaltner K, Oehlinger W, Schrei K, Redl H. A chronic pressure ulcer model in the nude mouse. Wound Repair Re-gen. 2009;17(4):480-484.
23. Chen WY, Rogers AA. Recent insights into the causes of chronic leg ul-ceration in venous diseases and implications on other types of chronic wounds. Wound Repair Regen. 2007;15(4):434-449.
24. Moore K, Huddleston E, Stacey MC, Harding KG. Venous leg ulcers-the search for a prognostic indicator. Int Wound J. 2007;4(2):163-172.
25. Schultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen. 2009;17(2):153-162.
26. Derosa G, D'Angelo A, Tinelli C, et al. Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in diabetic and healthy subjects. Diabetes Metab. 2007;33(2):129-134.
27. McDermott AM, Xiao TL, Kern TS, Murphy CJ. Non-enzymatic glycation in corneas from normal and diabetic donors and its efects on epithelial cell attachment in vitro. Optometry. 2003;74(7):443-452.
28. Yager DR, Kulina RA, Gilman LA. Wound fuids: a window into the wound environment? Int J Low Extrem Wounds. 2007;6(4):262-272.
29. Moseley R, Hilton JR, Waddington RJ, Harding KG, Stephens P, Thomas DW. Comparison of oxidative stress biomarker profles between acute and chronic wound environments. Wound Repair Regen. 2004;12(4):419-429.
30. Baxter CR. Immunologic reactions in chronic wounds. Am J Surg. 1994;167(1 suppl A):12S-14S.
31. Smith PC. The causes of skin damage and leg ulceration in chronic venous disease. Int J Lower Extrem Wounds. 2006;5(3):160-168.
32. Herrick SE, Sloan P, McGurk M, Freak L, McCollum CN, Ferguson MW. Sequential changes in histologic pattern and extracellular matrix deposition during the healing of chronic venous ulcers. Am J Pathol. 1992;141(5):1085-1095.
33. Phillips TJ, Palko MJ, Bhawan J. Histologic evaluation of chronic human wounds treated with hydrocolloid and nonhydrocolloid dressings. J Am Acad Dermatol. 1994;30(1):61-64.
34. Grinnell F, Zhu M. Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha1-proteinase inhibitor, and alpha2-macroglobulin. J Invest Dermatol. 1996;106(2):335-341.
35. Chen SM, Ward SI, Olutoye OO, Diegelmann R F, Cohen IK. Ability of chronic wound fuids to degrade peptide growth factors is associated with increased levels of elastase activity and diminished levels of proteinase inhibitors. Wound Repair Regen. 1997;5(1):23-32.
36. Rao CN, Ladin DA, Liu YY, Chilukuri K, Hou ZZ, Woodley DT. Alpha 1-antitrypsin is degraded and non-functional in chronic wounds but intact and functional in acute wounds: the inhibitor protects fbronectin from degradation by chronic wound fuid enzymes. J Invest Dermatol. 1995;105(4):572-578.
37. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med. 1989;320(6):365-376.
38. Stacey MC, Burnand KG, Mahmoud-Alexandroni M, Gafney PJ, Bhogal BS. Tissue and urokinase plasminogen activators in the environs of venous and ischaemic leg ulcers. Br J Surg. 1993;80(5):596-599.
39. Palolahti M, Lauharanta J, Stephens RW, Kuusela P, Vaheri A. Proteolytic activity in leg ulcer exudate. Exp Dermatol. 1993;2(1):29-37.
40. He Y, Young PK, Grinnell F. Identifcation of proteinase 3 as the major caseinolytic activity in acute human wound fuid. J Invest Dermatol. 1998;110(1):67-71
41. Tarlton J F, Bailey AJ, Crawford E, Jones D, Moore K, Harding KD. Prognostic value of markers of collagen remodeling in venous ulcers. Wound Repair Regen. 1999;7(5):347-355.
42. Wiegand C, Schönfelder U, Abel M, Ruth P, Kaatz M, Hipler UC. Protease and pro-infammatory cytokine concentrations are elevated in chronic compared to acute wounds and can be modulated by collagen type I in vitro. Arch Dermatol Res. 2010;302(6):419-428.
43. Herrick S, Ashcroft G, Ireland G, Horan M, McCollum C, Ferguson M. Up-regulation of elastase in acute wounds of healthy aged humans and chronic venous leg ulcers are associated with matrix degradation. Lab Invest. 1997;77(3):281-288.
44. Eming SA, Smola-Hess S, Kurschat P, Hirche D, Krieg T, Smola H. A novel property of povidone-iodine: inhibition of excessive protease levels in chronic non-healing wounds. J Invest Dermatol. 2006;126(12):2731-2733.
45. Hofman R, Starkey S, Coad J. Wound fuid from venous leg ulcers degrades plasminogen and reduces plasmin generation by keratinocytes. J Invest Dermatol. 1998;111(6):1140-1144.
46. Yager DR, Zhang LY, Liang HX, Diegelmann R F, Cohen IK. Wound fuids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fuids. J Invest Dermatol. 1996;107(5):743-748.
47. Wysocki AB, Kusakabe AO, Chang S, Tuan TL. Temporal expression of uro-kinase plasminogen activator, plasminogen activator inhibitor and gelatin-ase-B in chronic wound fuid switches from a chronic to acute wound profle with progression to healing. Wound Repair Regen. 1999;7(3):154-165.
48. Ladwig G P, Robson MC, Liu R, Kuhn MA, Muir DF, Schultz GS. Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metallo-proteinase-1 in wound fuids are inversely correlated with healing of pressure ulcers. Wound Repair Regen. 2002;10(1):26-37.
49. Wysocki AB, Staiano-Coico L, Grinnell F. Wound fuid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol. 1993;101(1):64-68.
50. Bullen EC, Longaker MT, Updike DL, et al. Tissue inhibitor of metallopro-teinases-1 is decreased and activated gelatinases are increased in chronic wounds. J Invest Dermatol. 1995;104(2):236-240.
51. Lobmann R, Ambrosch A, Schultz G, Waldmann K, Schiweck S, Lehnert H. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia. 2002;45(7):1011-1016.
52. Weckroth M, Vaheri A, Lauharanta J, Sorsa T, Konttinen YT. Matrix metal-loproteinases, gelatinase and collagenase, in chronic leg ulcers. J Invest Dermatol. 1996;106(5):1119-1124.
53. Nwomeh BC, Liang HX, Cohen IK, Yager DR. MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers. J Surg Res. 1999;81(2):189-195.
54. Utz ER, Elster EA, Tadaki DK, et al. Metalloproteinase expression is associated with traumatic wound failure. J Surg Res. 2010;159(2):633-639.
55. Moor AN, Vachon DJ, Gould LJ. Proteolytic activity in wound fuids and tissues derived from chronic venous leg ulcers. Wound Repair Regen. 2009;17(6):832-839.
56. Dechert TA, Ducale AE, Ward SI, Yager DR. Hyaluronan in human acute and chronic dermal wounds. Wound Repair Regen. 2006;14(3):252-258.
57. Providence KM, Higgins PJ. PAI-1 expression is required for epithelial cell migration in two distinct phases of in vitro wound repair. J Cell Physiol. 2004;200(2):297-308.
58. Vaalamo M, Leivo T, Saarialho-Kere U. Diferential expression of tissue inhibitors of metalloproteinases (TIMP-1,-2,-3, and-4) in normal and aberrant wound healing. Hum Pathol. 1999;30(7):795-802.
59. Hofman D, Moore K, Cooper R, Eagle M, Cooper S. Use of topical cortico-steroids on chronic leg ulcers. J Wound Care. 2007;16(5):227-230.
60. Clark SD, Kobayashi DK, Welgus HG. Regulation of the expression of tissue inhibitors of metalloproteinases and collagenase by retinoids and glu-cocorticoids in human fbroblasts. J Clin Invest. 1987;80(5):1280-1288.
61. Stechmiller J, Cowan L, Schultz G. The role of doxycycline as a matrix metalloproteinase inhibitor for the treatment of chronic wounds. Biol Res Nurs. 2010;11(4):336-344.
62. Chin GA, Thigpin TG, Perrin KJ, Moldawer LL, Schultz GS. Treatment of chronic ulcers in diabetic patients with a topical metalloproteinase inhibitor, doxycycline. WOUNDS. 2003;15(10):315-323.
63. Veves A, Sheehan P, Pham HT. A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers. Arch Surg. 2002;137(7):822-827.
64. Wollina U, Schmidt WD, Krönert C, Nelskamp C, Scheibe A, Fassler D. Some efects of a topical collagen-based matrix on the microcirculation and wound healing in patients with chronic venous leg ulcers: preliminary observations. Int J Low Extrem Wounds. 2005;4(4):214-224.
65. Mustoe TA, O'Shaughnessy K, Kloeters O. Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg. 2006;117(7 suppl):35S-41S.
66. Takahashi PY, Kiemele LJ, Chandra A, Cha SS, Targonski PV. A retrospective cohort study of factors that afect healing in long-term care residents with chronic wounds. Ostomy Wound Manage. 2009;55(1):32-37.
67. Brem H, Sheehan P, Rosenberg HJ, Schneider JS, Boulton AJ. Evidence-based protocol for diabetic foot ulcers. Plast Reconstr Surg. 2006;117(7 suppl):193S-211S.
68. Gardner SE, Frantz RA. Wound bioburden and infection-related complications in diabetic foot ulcers. Biol Res Nurs. 2008;10(1):44-53.
69. Markuson M, Hanson D, Anderson J, et al. The relationship between hemoglobin A(1c) values and healing time for lower extremity ulcers in individuals with diabetes. Adv Skin Wound Care. 2009;22(8):365-372.
70. Younger AS, Awwad MA, Kalla T P, de Vries G. Risk factors for failure of transmetatarsal amputation in diabetic patients: a cohort study. Foot Ankle Int 2009;30(12):1177-1182.
71. Ince P, Kendrick D, Game F, Jefcoate W. The association between baseline characteristics and the outcome of foot lesions in a UK population with diabetes. Diabet Med. 2007;24(9):977-981.
72. Snyder RJ, Cardinal M, Dauphinée DM, Stavosky J. A post-hoc analysis of reduction in diabetic foot ulcer size at 4 weeks as a predictor of healing by 12 weeks. Ostomy Wound Manage. 2010;56(3):44-50.
73. Coerper S, Beckert S, Küper MA, et al. Fifty percent area reduction after 4 weeks of treatment is a reliable indicator for healing-analysis of a single-center cohort of 704 diabetic patients. J Diabetes Complications. 2009;23(1):49-53.
74. Legerstee R. The 'chronic' wound debate. Wounds International 2009;1(1). Available at: www.woundsinternational.com/article.php?issueid=1&conte ntid=123&articleid=21&page=7. Accessed May 31, 2011.
75. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest. 2007;117(5):1219-1222.
76. Norris SO, Provo B, Stotts NA. Physiology of wound healing and risk factors that impede the healing process. AACN Clin Issues Crit Care Nurs. 1990;1(3):545-552.
77. Guo S, Dipietro LA. Factors afecting wound healing. J Dent Res. 2010;89(3):219-229.
78. Norman MU, Hickey MJ. Mechanisms of lymphocyte migration in autoimmune disease. Tissue Antigens. 2005;66(3):163-172.
79. Hanafusa T, Yamaguchi Y, Katayama I. Intractable wounds caused by arteriosclerosis obliterans with end-stage renal disease treated by aggressive debridement and epidermal grafting. J Am Acad Dermatol. 2007;57(2):322-326.
80. Fife CE, Buyukcakir C, Otto G, Shefeld P, Love T, Warriner R III. Factors infuencing the outcome of lower-extremity diabetic ulcers treated with hy-perbaric oxygen therapy. Wound Repair Regen. 2007;15(3):322-331.
81. Wilson JA, Clark JJ. Obesity: impediment to wound healing. Crit Care Nurs Q. 2003;26(2):119-132.
82. Lansdown AB. Nutrition 2: a vital consideration in the management of skin wounds. Br J Nurs. 2004;13(20):1199-1210.
83. Brem H, Lyder C. Protocol for the successful treatment of pressure ulcers. Am J Surg. 2004;188(1A suppl):9-17.
84. Reynolds TM. The future of nutrition and wound healing. J Tissue Viability. 2001;11(1):5-13.
85. Rathur HM, Boulton AJ. The diabetic foot. Clin Dermatol. 2007;25(1):109-120.
86. Jones KR, Fennie K. Factors infuencing pressure ulcer healing in adults over 50: an exploratory study. J Am Med Dir Assoc. 2007;8(6):378-387.
87. Inui S, Harada T, Nakajima T, Itami S. Two cases of pressure ulcer healing after liver transplantation in cirrhosis patients. J Dermatol. 2007;34(6):400-402.
88. Santilli JD, Santilli SM. Chronic critical limb ischemia: diagnosis, treatment and prognosis. Am Fam Physician. 1999;59(7):1899-1908.
89. Prompers L, Schnaper N, Apelqvist J, et al. Prediction of outcome in individuals with diabetic foot ulcers: focus on the diferences between individuals with an without peripheral arterial disease. The EURODALE study. Diabetologia. 2008;51(5):747-755.
90. Panuncialman J, Falanga V. Unusual causes of cutaneous ulceration. Surg Clin North Am. 2010;90(6):1161-1180.
91. Patt BT, Jarjoura D, Lambert L, et al. Prevalence of obstructive sleep ap-nea in patients with chronic wounds. J Clin Sleep Med. 2010;6(6):541-544.
92. Trent JT, Kirsner RS. Leg ulcers in sickle cell disease. Adv Skin Wound Care. 2004;17(8):410-416.
93. Boulton AJ. What you can't feel can hurt you. J Vasc Surg. 2010;52(3 suppl):28S-30S.
94. Kucukkaya M, Kuzgun U. Neuromuscular deformity: treatment with external fxation. Foot Ankle Clin. 2009;14(3):447-470.
95. Kudravi SA, Reed MJ. Aging, cancer, and wound healing. In Vivo. 2000;14(1):83-92.
96. Solowiej K, Mason V, Upton D. Psychological stress and pain in wound care, part 3: management. J Wound Care. 2010;19(4):153-155.
97. Snyder RJ. Venous leg ulcers in the elderly patient: associated stress, social support, and coping. Ostomy Wound Manage. 2006;52(9):58-68.
98. Jaul E. Non-healing wounds: the geriatric approach. Arch Gerontol Geriatr. 2009;49(2):224-226.
99. Oubre CM, Roy A, Toner C, Kalns J. Retrospective study of factors afect-ing non-healing of wounds during hyperbaric oxygen therapy. J Wound Care. 2007;16(6):245-250.
100. Salcido R. Smoking cessation: an important factor in wound care. Adv Skin Wound Care. 2007;20(11):576-578.
101. Sørensen LT, Hørby J, Friis E, Pilsgaard B, Jørgensen T. Smoking as a risk factor for wound healing and infection in breast cancer surgery. Eur J Surg Oncol. 2002;28(8):815-820.
102. Radek KA, Ranzer MJ, Dipietro LA. Brewing complications: the effect of acute ethanol exposure on wound healing. J Leukoc Biol. 2009;86(5):1125-1134.
103. McGuckin M, Torress-Cook A. Interventional patient hygiene for the wound care professional. Adv Skin Wound Care. 2009;22(9):416-420.
104. Van Hecke A, Grypdonck M, Defoor T. A review of why patients with leg ulcers do not adhere to treatment. J Clin Nurs. 2009;18(3):337-349.
105. Busti AJ, Hooper JS, Amaya CJ, Kazi S. Efects of perioperative antiin-fammatory and immunomodulating therapy on surgical wound healing. Pharmacotherapy. 2005;25(11):1566-1591.
106. Sirieix ME, Debure C, Baudot N, et al. Leg ulcers and hydroxyurea: forty-one cases. Arch Dermatol. 1999;135(7):818-820.
107. Regan PO. The impact of cancer and its treatment on wound healing. Wounds UK. 2007;3(2):87-95.
108. Telgenhof D, Shroot B. Cellular senescence mechanisms in chronic wound healing. Cell Death Differ. 2005;12(7):695-698.
109. Black CE, Costerton JW. Current concepts regarding the efect of wound microbial ecology and bioflms on wound healing. Surg Clin North Am. 2010;90(6):1147-1160.
110. Wolcott RD, Cox SB, Dowd SE. Healing and healing rates of chronic wounds in the age of molecular pathogen diagnostics. J Wound Care. 2010;19(7):272-281.
111. Beidler SK, Douillet CD, Berndt DF, Keagy BA, Rich PB, Marston WA. Infammatory cytokine levels in chronic venous insufciency ulcer tissue before and after compression therapy. J Vasc Surg. 2009;49(4):1013-1020.
112. Childress BB, Stechmiller JK. Role of nitric oxide in wound healing. Biol Res Nurs. 2002;4(1)5-15.
113. Agren MS, Mirastschijski U, Karlsmark T, Saarialho-Kere UK. Topical synthetic inhibitor of matrix metalloproteinases delays epidermal regeneration of human wounds. Exp Dermatol. 2001;10(5):337-348.
114. Smeets R, Ulrich D, Unglaub F, Wöltje M, Pallua N. Efect of oxidized regenerated cellulose/collagen matrix on proteases in wound exudate of patients with chronic venous ulceration. Int Wound J. 2008;5(2):195-203.
115. Xu J, Kim GM, Ahmed SH, et al. Glucocorticoid receptor-mediated suppression of activator protein-1 activation and matrix metalloproteinase expression after spinal cord injury. J Neurosci. 2001;21(1):92-97.
116. Widgerow AD. Chronic wound fuid-thinking outside the box. Wound Repair Regen. 2011;19(3):287-291.
117. Walker M, Bowler PG, Cochrane PA. In vitro studies to show sequestration of matrix metalloproteinases by silver-containing wound care products. Ostomy Wound Manage. 2007;53(9):18-25.
118. Stechmiller JK, Kilpadi DV, Childress B, Schultz GS. Efect of Vacuum-Assisted Closure Therapy on the expression of cytokines and proteases in wound fuid of adults with pressure ulcers. Wound Repair Regen. 2006;14(3):371-374.
119. ® Therapy in home-health or extended care patients. WOUNDS. 2006;18(5):119-126.
120. Gibson D, Cullen B, Legerstee R, Harding KG, Schultz G. MMPs made easy. Wounds Int. 2009;1(1):1-6.
121. Stegeman SA, van Doorn L P, Calame JJ, Steenvoorde P. Use of cadaveric donor skin to predict success of a defnitive split-thickness skin graft in complicated wounds. WOUNDS. 2010;22(11):284-288.
122. Treadwell TA, Willis AC, Brem H. Sickle cell ulcers. In: Baranoski S, Ayel-lo EA (eds). Wound Care Essentials. Practice Principles, 2nd ed. Ambler, PA: Lippincott Williams & Wilkins;2008:363-372.
123. US Food and Drug Administration. Medical devices. Clinical Laboratory Improvement Amendments (CLIA). Available at: www.fda.gov/Medi-calDevices/ DeviceRegulationandGuidance/IVDRegulatoryAssistance/ucm124105htm. Accessed June 3, 2011.
124. Carter MJ. Evidence-based medicine: an overview of key concepts. Os-tomy Wound Manage. 2010;56(4):68-85.