Skip to main content

Traditional and Nontraditional Evaluation of Wound Healing Process

  • Chapter
  • First Online:
Chronic Wounds, Wound Dressings and Wound Healing

Abstract

Wound healing is a dynamic, interactive cascade of molecular, cellular, and biochemical processes. Even though many therapeutic interventions are utilized, physician decisions are hampered by the lack of objective and convenient methods to monitor treatment effects and assess wound healing. Wound evaluation has traditionally relied on visual assessment by the trained clinician; however, new aspects are providing objective assessment modalities. As a gold standard methodology for wound healing assessment, that procedure should be applicable to all types of wounds, proven reliable, accurate, and precise. Moreover, it should be sensible and reflect the progression of the whole healing spectrum with time. Simplicity, safety for patients, and convenience for clinicians should also be considered as important factors. Since the assessment needs to be performed regularly, standard methodologies should be affordable, should be time efficient, and, at the same time, should not require cumbersome equipment. To date, no one method meets all of these criteria, and it is necessary for clinicians to understand the type of wound, sample size, results obtained, advantages, and limitations of each technique in order to choose the optimum tool for wound evaluation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. U.S. Department of Health and Human Services Food and Drug Administration (2006) Guidance for industry: chronic cutaneous ulcer and burn wounds developing products for treatment

    Google Scholar 

  2. Reynolds T, Russell L (2004) Evaluation of a wound dressing using different research methods. Br J Nurs 13(11):S21–S24

    PubMed  Google Scholar 

  3. Schultz GS, Sibbald RG, Falanga V, Ayello EA, Dowsett C, Harding K, Romanelli M, Stacey MC, Teot L, Vanscheidt W (2003) Wound bed preparation: a systematic approach to wound management. Wound Repair Regen 11(Suppl 1):S1–S28

    PubMed  Google Scholar 

  4. St-Supery V, Tahiri Y, Sampalis J, Brutus JP, Harris PG, Nikolis A (2011) Wound healing assessment: does the ideal methodology for a research setting exist? Ann Plast Surg 67(2):193–200

    CAS  PubMed  Google Scholar 

  5. Polit D, Hungler B (1999) Nursing Research: Principles and Methods. Lippincott, Michigan

    Google Scholar 

  6. Langemo D, Melland H, Olson B, Hanson D, Hunter S, Henly S, Thompson P (2001) Comparison of 2 wound volume measurement methods. Adv Skin Wound Care 14(4):190–196

    CAS  PubMed  Google Scholar 

  7. Lazarus GS, Cooper DM, Knighton DR, Margolis DJ, Pecoraro RE, Rodeheaver G, Robson MC (1994) Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 130(4):489–493

    CAS  PubMed  Google Scholar 

  8. Stromberg K, Chapekar MS, Goldman BA, Chambers WA, Cavagnaro JA (1994) Regulatory concerns in the development of topical recombinant ophthalmic and cutaneous wound healing biologics. Wound Repair Regen 2(3):155–164

    CAS  PubMed  Google Scholar 

  9. Keast DH, Bowering CK, Evans AW, Mackean GL, Burrows C, D'Souza L (2004) MEASURE: A proposed assessment framework for developing best practice recommendations for wound assessment. Wound Repair Regen 12(3 Suppl):S1–S17

    PubMed  Google Scholar 

  10. Gottrup F, Apelqvist J, Price P, European Wound Management Association Patient Outcome G (2010) Outcomes in controlled and comparative studies on non-healing wounds: recommendations to improve the quality of evidence in wound management. J Wound Care 19(6):237–268

    CAS  PubMed  Google Scholar 

  11. Flanagan M (2003) Improving accuracy of wound measurement in clinical practice. Ostomy Wound Manage 49(10):28–40

    PubMed  Google Scholar 

  12. Ahn C, Salcido RS (2008) Advances in wound photography and assessment methods. Adv Skin Wound Care 21(2):85–93

    PubMed  Google Scholar 

  13. Thomas AC, Wysocki AB (1990) The healing wound: a comparison of three clinically useful methods of measurement. Decubitus 3(1):18–20,24–5

    Google Scholar 

  14. Goldman RJ, Salcido R (2002) More than one way to measure a wound: an overview of tools and techniques. Adv Skin Wound Care 15(5):236–243

    PubMed  Google Scholar 

  15. Ferrell BA (1997) Pressure ulcers. Assessment of healing. Clin Geriatr Med 13(3):575–586

    CAS  PubMed  Google Scholar 

  16. Johnson M, Miller R (1996) Measuring healing in leg ulcers: practice considerations. Appl Nurs Res 9(4):204–208

    CAS  PubMed  Google Scholar 

  17. Charles H (1998) Wound assessment: measuring the area of a leg ulcer. Br J Nurs 7(13):765–768, 70, 72

    CAS  PubMed  Google Scholar 

  18. Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9(7):671–675

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Goldman RJ, Brewley BI, Golden MA (2002) Electrotherapy reoxygenates inframalleolar ischemic wounds on diabetic patients: a case series. Adv Skin Wound Care 15(3):112–120

    PubMed  Google Scholar 

  20. Joseph E, Hamori C, Bergman S, Roaf E, Swann N, Anastasi G (2000) A prospective randomized trial of vacuum-assisted closure versus standard therapy of chronic nonhealing wounds. Wounds 12(3):60–67

    Google Scholar 

  21. Cutler NR, George R, Seifert RD, Brunelle R, Sramek JJ, McNeill K, Boyd WM (1993) Comparison of quantitative methodologies to define chronic pressure ulcer measurements. Decubitus 6(6):22–30

    CAS  PubMed  Google Scholar 

  22. Chang AC, Dearman B, Greenwood JE (2011) A comparison of wound area measurement techniques: visitrak versus photography. Eplasty 11:e18

    PubMed  PubMed Central  Google Scholar 

  23. Palmer R (1989) A digital video technique for radiographs and monitoring ulcers. J Photographic Sci 37:65–67

    Google Scholar 

  24. Eriksson G, Eklund AE, Torlegard K, Dauphin E (1979) Evaluation of leg ulcer treatment with stereophotogrammetry. A pilot study. Br J Dermatol 101(2):123–131

    CAS  PubMed  Google Scholar 

  25. Wysocki AB (1996) Wound measurement. Int J Dermatol 35(2):82–91

    CAS  PubMed  Google Scholar 

  26. Thawer HA, Houghton PE, Woodbury MG, Keast D, Campbell K (2002) A comparison of computer-assisted and manual wound size measurement. Ostomy Wound Manage 48(10):46–53

    PubMed  Google Scholar 

  27. Kundin JI (1989) A new way to size up a wound. Am J Nurs 89(2):206–207

    CAS  PubMed  Google Scholar 

  28. Kundin JI (1985) Designing and developing a new measuring instrument. Perioper Nurs Q 1(4):40–45

    CAS  PubMed  Google Scholar 

  29. Häkkinen L, Larjava H, Koivisto L (2011) Granulation tissue formation and remodeling. Endod Topics 24(1):94–129

    Google Scholar 

  30. Hofman D (2007) The autolytic debridement of venous leg ulcers. Wound Essentials 2:68–73

    Google Scholar 

  31. Gray D, White R, Cooper C, Kingsley A (2004) The wound healing continuum, an aid to clinical decision making and clinical audit. Appl Wound Manag Suppl Wounds UK:9–12

    Google Scholar 

  32. Gray D, White R, Cooper P, Kingsley A (2005) Understanding applied wound management. Wounds UK 1(1):62–68

    Google Scholar 

  33. Hansen GL, Sparrow EM, Kokate JY, Leland KJ, Iaizzo PA (1997) Wound status evaluation using color image processing. IEEE Trans Med Imaging 16(1):78–86

    CAS  PubMed  Google Scholar 

  34. Herbin M, Bon FX, Venot A, Jeanlouis F, Dubertret ML, Dubertret L, Strauch G (1993) Assessment of healing kinetics through true color image processing. IEEE Trans Med Imaging 12(1):39–43

    CAS  PubMed  Google Scholar 

  35. Cohen M, Giladi M, Mayo A, Shafir R (1998) The granulometer--a pocket scale for the assessment of wound healing. Ann Plast Surg 40(6):641–645

    CAS  PubMed  Google Scholar 

  36. Bon FX, Briand E, Guichard S, Couturaud B, Revol M, Servant JM, Dubertret L (2000) Quantitative and kinetic evolution of wound healing through image analysis. IEEE Trans Med Imaging 19(7):767–772

    CAS  PubMed  Google Scholar 

  37. Tong A (1999) The identification and treatment of slough. J Wound Care 8(7):338–339

    CAS  PubMed  Google Scholar 

  38. Mekkes JR, Westerhof W (1995) Image processing in the study of wound healing. Clin Dermatol 13(4):401–407

    CAS  PubMed  Google Scholar 

  39. Wolvos T, Livingston M (2013) Wound fluid management in wound care: The role of a hydroconductive dressing. Wounds 25(1):7–14

    PubMed  Google Scholar 

  40. Wild T, Prinz M, Fortner N, Krois W, Sahora K, Stremitzer S, Hoelzenbein T (2008) Digital measurement and analysis of wounds based on colour segmentation. Eur Surg 40(1):5–10

    Google Scholar 

  41. Jelinek H, Prinz M, Wild T (2013) A digital assessment and documentation tool evaluated for daily podiatric wound practice. Wounds 25(1):1–6

    CAS  PubMed  Google Scholar 

  42. Lammers G, Verhaegen PD, Ulrich MM, Schalkwijk J, Middelkoop E, Weiland D, Nillesen ST, Van Kuppevelt TH, Daamen WF (2011) An overview of methods for the in vivo evaluation of tissue-engineered skin constructs. Tissue Eng Part B Rev 17(1):33–55

    CAS  PubMed  Google Scholar 

  43. Diffey BL, Oliver RJ, Farr PM (1984) A portable instrument for quantifying erythema induced by ultraviolet radiation. Br J Dermatol 111(6):663–672

    CAS  PubMed  Google Scholar 

  44. World Union of Wound Healing Societies (WUoWHS) (2008) Principles of best practice: Wound infection in clinical practice. An international consensus. MEP Ltd, London

    Google Scholar 

  45. Swanson T, Haesler E, Angel D, Sussman G. Wound infection in clinical practice: principles of best practice. 2016 www.woundsaustralia.com.au/journal/2404_02.pdf. Accessed 5 Jul 2017

  46. Healy B, Freedman A (2006) ABC of wound healing: Infections. BMJ 332(7545):838–841

    PubMed  PubMed Central  Google Scholar 

  47. Kingsley A (2003) The wound infection continuum and its application to clinical practice. Ostomy Wound Manage 49(7A Suppl):1–7

    PubMed  Google Scholar 

  48. Bowler PG (2002) Wound pathophysiology, infection and therapeutic options. Ann Med 34(6):419–427

    CAS  PubMed  Google Scholar 

  49. Thomas Hess C (2011) Checklist for factors affecting wound healing. Adv Skin Wound Care 24(4):192

    PubMed  Google Scholar 

  50. Fierheller M, Sibbald RG (2010) A clinical investigation into the relationship between increased periwound skin temperature and local wound infection in patients with chronic leg ulcers. Adv Skin Wound Care 23(8):369–379

    PubMed  Google Scholar 

  51. Percival SL, McCarty S, Hunt JA, Woods EJ (2014) The effects of pH on wound healing, biofilms, and antimicrobial efficacy. Wound Repair Regen 22(2):174–186

    PubMed  Google Scholar 

  52. Lambers H, Piessens S, Bloem A, Pronk H, Finkel P (2006) Natural skin surface pH is on average below 5, which is beneficial for its resident flora. Int J Cosmet Sci 28(5):359–370

    CAS  PubMed  Google Scholar 

  53. Schneider LA, Korber A, Grabbe S, Dissemond J (2007) Influence of pH on wound-healing: a new perspective for wound-therapy? Arch Dermatol Res 298(9):413–420

    PubMed  Google Scholar 

  54. Lengheden A, Jansson L (1995) pH effects on experimental wound healing of human fibroblasts in vitro. Eur J Oral Sci 103(3):148–155

    CAS  PubMed  Google Scholar 

  55. Glibbery A, Mani R (1992) pH in leg ulcers. Int J Microcirc Clin Exp 2(11):109

    Google Scholar 

  56. Hasatsri S, Aramwit P (2017) Nontraditional methods to evaluate wound healing. Dermatol Surg 43(3):342–350

    CAS  PubMed  Google Scholar 

  57. Imhof RE, De Jesus ME, Xiao P, Ciortea LI, Berg EP (2009) Closed-chamber transepidermal water loss measurement: microclimate, calibration and performance. Int J Cosmet Sci 31(2):97–118

    CAS  PubMed  Google Scholar 

  58. Rogiers V, Group E (2001) EEMCO guidance for the assessment of transepidermal water loss in cosmetic sciences. Skin Pharmacol Appl Ski Physiol 14(2):117–128

    CAS  Google Scholar 

  59. Siritientong T, Angspatt A, Ratanavaraporn J, Aramwit P (2014) Clinical potential of a silk sericin-releasing bioactive wound dressing for the treatment of split-thickness skin graft donor sites. Pharm Res 31(1):104–116

    CAS  PubMed  Google Scholar 

  60. Hasatsri S, Angspatt A, Aramwit P (2015) Randomized clinical trial of the innovative bilayered wound dressing made of silk and gelatin: safety and efficacy tests using a split-thickness skin graft model. Evid Based Complement Alternat Med 2015:1–8

    Google Scholar 

  61. Trookman N, Rizer RL, Weber T (2011) Treatment of minor wounds from dermatologic procedures: a comparison of three topical wound care ointments using a laser wound model. J Am Acad Dermatol 64(3):S8–S15

    CAS  PubMed  Google Scholar 

  62. Na JI, Choi JW, Choi HR, Jeong JB, Park KC, Youn SW, Huh CH (2011) Rapid healing and reduced erythema after ablative fractional carbon dioxide laser resurfacing combined with the application of autologous platelet-rich plasma. Dermatol Surg 37(4):463–468

    CAS  PubMed  Google Scholar 

  63. Atiyeh BS, El-Musa KA, Dham R (2003) Scar quality and physiologic barrier function restoration after moist and moist-exposed dressings of partial-thickness wounds. Dermatol Surg 29(1):14–20

    PubMed  Google Scholar 

  64. Czaika V, Alborova A, Richter H, Sterry W, Vergou T, Antoniou C, Lademann J, Koch S (2012) Comparison of transepidermal water loss and laser scanning microscopy measurements to assess their value in the characterization of cutaneous barrier defects. Skin Pharmacol Physiol 25(1):39–46

    CAS  PubMed  Google Scholar 

  65. Kottner J, Lichterfeld A, Blume-Peytavi U (2013) Transepidermal water loss in young and aged healthy humans: a systematic review and meta-analysis. Arch Dermatol Res 305(4):315–323

    PubMed  Google Scholar 

  66. Pinnagoda J, Tupker RA, Agner T, Serup J (1990) Guidelines for transepidermal water loss (TEWL) measurement. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis 22(3):164–178

    CAS  PubMed  Google Scholar 

  67. Wilhelm KP, Cua AB, Maibach HI (1991) Skin aging. Effect on transepidermal water loss, stratum corneum hydration, skin surface pH, and casual sebum content. Arch Dermatol 127(12):1806–1809

    CAS  PubMed  Google Scholar 

  68. Luebberding S, Krueger N, Kerscher M (2013) Age-related changes in skin barrier function - quantitative evaluation of 150 female subjects. Int J Cosmet Sci 35(2):183–190

    CAS  PubMed  Google Scholar 

  69. Kekonen A, Bergelin M, Eriksson J, Viik J (2015) A quantitative method for monitoring wound healing. Int J Bioelectromagn 17(1):36–41

    Google Scholar 

  70. Grimnes S (1983) Impedance measurement of individual skin surface electrodes. Med Biol Eng Comput 21(6):750–755

    CAS  PubMed  Google Scholar 

  71. McColl D, Cartlidge B, Connolly P (2007) Real-time monitoring of moisture levels in wound dressings in vitro: an experimental study. Int J Surg 5(5):316–322

    PubMed  Google Scholar 

  72. Lawler JC, Davis MJ, Griffith EC (1960) Electrical characteristics of the skin. The impedance of the surface sheath and deep tissues. J Invest Dermatol 34:301–308

    CAS  PubMed  Google Scholar 

  73. Grove GL, Kligman AM (1983) Age-associated changes in human epidermal cell renewal. J Gerontol 38(2):137–142

    CAS  PubMed  Google Scholar 

  74. Holzle E, Plewig G (1977) Effects of dermatitis, stripping, and steroids on the morphology of corneocytes. A new bioassay. J Invest Dermatol 68(6):350–356

    CAS  PubMed  Google Scholar 

  75. Guz NV, Gaikwad RM, Dokukin ME, Sokolov I (2009) A novel in vitro stripping method to study geometry of corneocytes with fluorescent microscopy: example of aging skin. Skin Res Technol 15(4):379–383

    CAS  PubMed  Google Scholar 

  76. Lee S, Park Y, Kang J (1982) The experimental study on keratinocytes of chronically irritated skin (II). Yonsei Med J 23(1):80–83

    CAS  PubMed  Google Scholar 

  77. Loppnow H, Bil R, Hirt S, Schonbeck U, Herzberg M, Werdan K, Rietschel ET, Brandt E, Flad HD (1998) Platelet-derived interleukin-1 induces cytokine production, but not proliferation of human vascular smooth muscle cells. Blood 91(1):134–141

    CAS  PubMed  Google Scholar 

  78. Fong Y, Moldawer LL, Marano M, Wei H, Barber A, Manogue K, Tracey KJ, Kuo G, Fischman DA, Cerami A et al (1989) Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. Am J Phys 256(3 Pt 2):R659–R665

    CAS  Google Scholar 

  79. Sauder DN, Kilian PL, McLane JA, Quick TW, Jakubovic H, Davis SC, Eaglstein WH, Mertz PM (1990) Interleukin-1 enhances epidermal wound healing. Lymphokine Res 9(4):465–473

    CAS  PubMed  Google Scholar 

  80. Thomay AA, Daley JM, Sabo E, Worth PJ, Shelton LJ, Harty MW, Reichner JS, Albina JE (2009) Disruption of interleukin-1 signaling improves the quality of wound healing. Am J Pathol 174(6):2129–2136

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Trengove NJ, Bielefeldt-Ohmann H, Stacey MC (2000) Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen 8(1):13–25

    CAS  PubMed  Google Scholar 

  82. Barone EJ, Yager DR, Pozez AL, Olutoye OO, Crossland MC, Diegelmann RF, Cohen IK (1998) Interleukin-1alpha and collagenase activity are elevated in chronic wounds. Plast Reconstr Surg 102(4):1023–1027

    CAS  PubMed  Google Scholar 

  83. Ishida Y, Kondo T, Kimura A, Matsushima K, Mukaida N (2006) Absence of IL-1 receptor antagonist impaired wound healing along with aberrant NF-kappaB activation and a reciprocal suppression of TGF-beta signal pathway. J Immunol 176(9):5598–5606

    CAS  PubMed  Google Scholar 

  84. McFarland-Mancini MM, Funk HM, Paluch AM, Zhou M, Giridhar PV, Mercer CA, Kozma SC, Drew AF (2010) Differences in wound healing in mice with deficiency of IL-6 versus IL-6 receptor. J Immunol 184(12):7219–7228

    CAS  PubMed  Google Scholar 

  85. Lin ZQ, Kondo T, Ishida Y, Takayasu T, Mukaida N (2003) Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol 73(6):713–721

    CAS  PubMed  Google Scholar 

  86. Gallucci RM, Simeonova PP, Matheson JM, Kommineni C, Guriel JL, Sugawara T, Luster MI (2000) Impaired cutaneous wound healing in interleukin-6-deficient and immunosuppressed mice. FASEB J 14(15):2525–2531

    CAS  PubMed  Google Scholar 

  87. Gallucci RM, Sugawara T, Yucesoy B, Berryann K, Simeonova PP, Matheson JM, Luster MI (2001) Interleukin-6 treatment augments cutaneous wound healing in immunosuppressed mice. J Interf Cytokine Res 21(8):603–609

    CAS  Google Scholar 

  88. Kuhn KA, Manieri NA, Liu TC, Stappenbeck TS (2014) IL-6 stimulates intestinal epithelial proliferation and repair after injury. PLoS One 9(12):e114195

    PubMed  PubMed Central  Google Scholar 

  89. Arranz-Valsero I, Soriano-Romaní L, García-Posadas L, López-García A, Diebold Y (2014) IL-6 as a corneal wound healing mediator in an in vitro scratch assay. Exp Eye Res 125:183–192

    CAS  PubMed  Google Scholar 

  90. Yamamoto T, Eckes B, Krieg T (2001) Effect of interleukin-10 on the gene expression of type I collagen, fibronectin, and decorin in human skin fibroblasts: differential regulation by transforming growth factor-beta and monocyte chemoattractant protein-1. Biochem Biophys Res Commun 281(1):200–205

    CAS  PubMed  Google Scholar 

  91. Ricchetti ET, Reddy SC, Ansorge HL, Zgonis MH, Van Kleunen JP, Liechty KW, Soslowsky LJ, Beredjiklian PK (2008) Effect of interleukin-10 overexpression on the properties of healing tendon in a murine patellar tendon model. J Hand Surg Am 33(10):1843–1852

    PubMed  Google Scholar 

  92. Verma SK, Krishnamurthy P, Barefield D, Singh N, Gupta R, Lambers E, Thal M, Mackie A, Hoxha E, Ramirez V, Qin G, Sadayappan S, Ghosh AK, Kishore R (2012) Interleukin-10 treatment attenuates pressure overload-induced hypertrophic remodeling and improves heart function via signal transducers and activators of transcription 3-dependent inhibition of nuclear factor-kappaB. Circulation 126(4):418–429

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Peranteau WH, Zhang L, Muvarak N, Badillo AT, Radu A, Zoltick PW, Liechty KW (2008) IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation. J Invest Dermatol 128(7):1852–1860

    CAS  PubMed  Google Scholar 

  94. Kieran I, Knock A, Bush J, So K, Metcalfe A, Hobson R, Mason T, O’Kane S, Ferguson M (2013) Interleukin-10 reduces scar formation in both animal and human cutaneous wounds: results of two preclinical and phase II randomized control studies. Wound Repair Regen 21(3):428–436

    PubMed  Google Scholar 

  95. Wise LM, Stuart GS, Real NC, Fleming SB, Mercer AA (2014) Orf virus IL-10 accelerates wound healing while limiting inflammation and scarring. Wound Repair Regen 22(3):356–367

    PubMed  Google Scholar 

  96. Chen X, Thibeault SL (2010) Role of tumor necrosis factor-alpha in wound repair in human vocal fold fibroblasts. Laryngoscope 120(9):1819–1825

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Vilcek J, Palombella VJ, Henriksen-DeStefano D, Swenson C, Feinman R, Hirai M, Tsujimoto M (1986) Fibroblast growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors. J Exp Med 163(3):632–643

    CAS  PubMed  Google Scholar 

  98. Sasaki M, Kashima M, Ito T, Watanabe A, Izumiyama N, Sano M, Kagaya M, Shioya T, Miura M (2000) Differential regulation of metalloproteinase production, proliferation and chemotaxis of human lung fibroblasts by PDGF, interleukin-1beta and TNF-alpha. Mediat Inflamm 9(3–4):155–160

    CAS  Google Scholar 

  99. Kaiser GC, Polk DB (1997) Tumor necrosis factor alpha regulates proliferation in a mouse intestinal cell line. Gastroenterology 112(4):1231–1240

    CAS  PubMed  Google Scholar 

  100. Siqueira MF, Li J, Chehab L, Desta T, Chino T, Krothpali N, Behl Y, Alikhani M, Yang J, Braasch C, Graves DT (2010) Impaired wound healing in mouse models of diabetes is mediated by TNF-alpha dysregulation and associated with enhanced activation of forkhead box O1 (FOXO1). Diabetologia 53(2):378–388

    CAS  PubMed  Google Scholar 

  101. Papanas N, Maltezos E (2007) Growth factors in the treatment of diabetic foot ulcers: new technologies, any promises? Int J Low Extrem Wounds 6(1):37–53

    CAS  PubMed  Google Scholar 

  102. Eming SA, Martin P, Tomic-Canic M (2014) Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med 6(265):265sr6

    PubMed  PubMed Central  Google Scholar 

  103. Smiell JM, Wieman TJ, Steed DL, Perry BH, Sampson AR, Schwab BH (1999) 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. Wound Repair Regen 7(5):335–346

    CAS  PubMed  Google Scholar 

  104. Greenhalgh DG, Sprugel KH, Murray MJ, Ross R (1990) PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am J Pathol 136(6):1235–1246

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Greenhalgh DG, Hummel RP, Albertson S, Breeden MP (1993) Synergistic actions of platelet-derived growth factor and the insulin-like growth factors in vivo. Wound Repair Regen 1(2):69–81

    CAS  PubMed  Google Scholar 

  106. Pierce GF, Tarpley JE, Yanagihara D, Mustoe TA, Fox GM, Thomason A (1992) Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair. Am J Pathol 140(6):1375–1388

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Yun YR, Won JE, Jeon E, Lee S, Kang W, Jo H, Jang JH, Shin US, Kim HW (2010) Fibroblast growth factors: biology, function, and application for tissue regeneration. J Tissue Eng 2010:218142

    PubMed  PubMed Central  Google Scholar 

  108. Shi HX, Lin C, Lin BB, Wang ZG, Zhang HY, Wu FZ, Cheng Y, Xiang LJ, Guo DJ, Luo X, Zhang GY, Fu XB, Bellusci S, Li XK, Xiao J (2013) The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo. PLoS One 8(4):e59966

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Werner S, Smola H, Liao X, Longaker MT, Krieg T, Hofschneider PH, Williams LT (1994) The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science 266(5186):819–822

    CAS  PubMed  Google Scholar 

  110. Shirakata Y, Kimura R, Nanba D, Iwamoto R, Tokumaru S, Morimoto C, Yokota K, Nakamura M, Sayama K, Mekada E, Higashiyama S, Hashimoto K (2005) Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing. J Cell Sci 118(Pt 11):2363–2370

    CAS  PubMed  Google Scholar 

  111. Oda K, Matsuoka Y, Funahashi A, Kitano H (2005) A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 1:2005.0010

    PubMed  PubMed Central  Google Scholar 

  112. Jiang CK, Magnaldo T, Ohtsuki M, Freedberg IM, Bernerd F, Blumenberg M (1993) Epidermal growth factor and transforming growth factor alpha specifically induce the activation- and hyperproliferation-associated keratins 6 and 16. Proc Natl Acad Sci U S A 90(14):6786–6790

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Haase I, Evans R, Pofahl R, Watt FM (2003) Regulation of keratinocyte shape, migration and wound epithelialization by IGF-1- and EGF-dependent signalling pathways. J Cell Sci 116(Pt 15):3227–3238

    CAS  PubMed  Google Scholar 

  114. Reckenbeil J, Kraus D, Stark H, Rath-Deschner B, Jager A, Wenghoefer M, Winter J, Gotz W (2017) Insulin-like growth factor 1 (IGF1) affects proliferation and differentiation and wound healing processes in an inflammatory environment with p38 controlling early osteoblast differentiation in periodontal ligament cells. Arch Oral Biol 73:142–150

    CAS  PubMed  Google Scholar 

  115. Brown DL, Kane CD, Chernausek SD, Greenhalgh DG (1997) Differential expression and localization of insulin-like growth factors I and II in cutaneous wounds of diabetic and nondiabetic mice. Am J Pathol 151(3):715–724

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Galiano RD, Tepper OM, Pelo CR, Bhatt KA, Callaghan M, Bastidas N, Bunting S, Steinmetz HG, Gurtner GC (2004) Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol 164(6):1935–1947

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Tan Q, Chen B, Yan X, Lin Y, Xiao Z, Hou X, Dai J (2014) Promotion of diabetic wound healing by collagen scaffold with collagen-binding vascular endothelial growth factor in a diabetic rat model. J Tissue Eng Regen Med 8(3):195–201

    CAS  PubMed  Google Scholar 

  118. Pastar I, Stojadinovic O, Krzyzanowska A, Barrientos S, Stuelten C, Zimmerman K, Blumenberg M, Brem H, Tomic-Canic M (2010) Attenuation of the transforming growth factor beta-signaling pathway in chronic venous ulcers. Mol Med 16(3–4):92–101

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122(1):103–111

    CAS  PubMed  Google Scholar 

  120. Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH (1987) Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med 165(1):251–256

    CAS  PubMed  Google Scholar 

  121. Ishida Y, Gao JL, Murphy PM (2008) Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function. J Immunol 180(1):569–579

    CAS  PubMed  Google Scholar 

  122. Satish L, Yager D, Wells A (2003) Glu-Leu-Arg-negative CXC chemokine interferon gamma inducible protein-9 as a mediator of epidermal-dermal communication during wound repair. J Invest Dermatol 120(6):1110–1117

    CAS  PubMed  Google Scholar 

  123. Yates CC, Whaley D, Kulasekeran P, Hancock WW, Lu B, Bodnar R, Newsome J, Hebda PA, Wells A (2007) Delayed and deficient dermal maturation in mice lacking the CXCR3 ELR-negative CXC chemokine receptor. Am J Pathol 171(2):484–495

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Li YY, Feldman AM, Sun Y, McTiernan CF (1998) Differential expression of tissue inhibitors of metalloproteinases in the failing human heart. Circulation 98(17):1728–1734

    CAS  PubMed  Google Scholar 

  125. Li YY, McTiernan CF, Feldman AM (2000) Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovasc Res 46(2):214–224

    CAS  PubMed  Google Scholar 

  126. Efron PA, Moldawer LL (2004) Cytokines and wound healing: the role of cytokine and anticytokine therapy in the repair response. J Burn Care Rehabil 25(2):149–160

    PubMed  Google Scholar 

  127. Behm B, Babilas P, Landthaler M, Schreml S (2012) Cytokines, chemokines and growth factors in wound healing. J Eur Acad Dermatol Venereol 26(7):812–820

    CAS  PubMed  Google Scholar 

  128. Schröder J-M (1995) Cytokine Networks in the Skin. J Invest Dermatol 105(1):S20–SS4

    Google Scholar 

  129. Weber A, Wasiliew P, Kracht M (2010) Interleukin-1beta (IL-1 beta) processing pathway. Sci Signal 3(105):cm2

    PubMed  Google Scholar 

  130. Grellner W, Georg T, Wilske J (2000) Quantitative analysis of proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in human skin wounds. Forensic Sci Int 113(1–3):251–264

    CAS  PubMed  Google Scholar 

  131. Mast BA, Schultz GS (1996) Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair Regen 4(4):411–420

    CAS  PubMed  Google Scholar 

  132. Van Snick J (1990) Interleukin-6: an overview. Annu Rev Immunol 8:253–278

    PubMed  Google Scholar 

  133. Ford HR, Hoffman RA, Wing EJ, Magee D, McIntyre L, Simmons RL (1989) Characterization of wound cytokines in the sponge matrix model. Arch Surg 124(12):1422–1428

    CAS  PubMed  Google Scholar 

  134. Barker JN, Mitra RS, Griffiths CE, Dixit VM, Nickoloff BJ (1991) Keratinocytes as initiators of inflammation. Lancet 337(8735):211–214

    CAS  PubMed  Google Scholar 

  135. Hubner G, Brauchle M, Smola H, Madlener M, Fassler R, Werner S (1996) Differential regulation of pro-inflammatory cytokines during wound healing in normal and glucocorticoid-treated mice. Cytokine 8(7):548–556

    CAS  PubMed  Google Scholar 

  136. Kondo T, Ohshima T (1996) The dynamics of inflammatory cytokines in the healing process of mouse skin wound: a preliminary study for possible wound age determination. Int J Legal Med 108(5):231–236

    CAS  PubMed  Google Scholar 

  137. Grossman RM, Krueger J, Yourish D, Granelli-Piperno A, Murphy DP, May LT, Kupper TS, Sehgal PB, Gottlieb AB (1989) Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proc Natl Acad Sci U S A 86(16):6367–6371

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Koch AE, Kronfeld-Harrington LB, Szekanecz Z, Cho MM, Haines GK, Harlow LA, Strieter RM, Kunkel SL, Massa MC, Barr WG et al (1993) In situ expression of cytokines and cellular adhesion molecules in the skin of patients with systemic sclerosis. Their role in early and late disease. Pathobiology 61(5–6):239–246

    CAS  PubMed  Google Scholar 

  139. Fugger L, Morling N, Bendtzen K, Ryder L, Andersen V, Heilman C, Karup Pedersen F, Friis J, Halbert P, Svejgaard A (1989) IL-6 gene polymorphism in rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, and in healthy Danes. J Immunogenet 16(6):461–465

    CAS  PubMed  Google Scholar 

  140. Shingu M, Isayama T, Yasutake C, Naono T, Nobunaga M, Tomari K, Horie K, Goto Y (1994) Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation. Inflammation 18(6):613–623

    CAS  PubMed  Google Scholar 

  141. Lotz M, Guerne PA (1991) Interleukin-6 induces the synthesis of tissue inhibitor of metalloproteinases-1/erythroid potentiating activity (TIMP-1/EPA). J Biol Chem 266(4):2017–2020

    CAS  PubMed  Google Scholar 

  142. Sato T, Ito A, Mori Y (1990) Interleukin 6 enhances the production of tissue inhibitor of metalloproteinases (TIMP) but not that of matrix metalloproteinases by human fibroblasts. Biochem Biophys Res Commun 170(2):824–829

    CAS  PubMed  Google Scholar 

  143. An L, Dong GQ, Gao Q, Zhang Y, Hu LW, Li JH, Liu Y (2010) Effects of UVA on TNF-alpha, IL-1beta, and IL-10 expression levels in human keratinocytes and intervention studies with an antioxidant and a JNK inhibitor. Photodermatol Photoimmunol Photomed 26(1):28–35

    CAS  PubMed  Google Scholar 

  144. King A, Balaji S, Le LD, Crombleholme TM, Keswani SG (2014) Regenerative wound healing: the role of interleukin-10. Adv Wound Care (New Rochelle) 3(4):315–323

    Google Scholar 

  145. Gordon A, Kozin ED, Keswani SG, Vaikunth SS, Katz AB, Zoltick PW, Favata M, Radu AP, Soslowsky LJ, Herlyn M, Crombleholme TM (2008) Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation. Wound Repair Regen 16(1):70–79

    PubMed  Google Scholar 

  146. Torti FM, Dieckmann B, Beutler B, Cerami A, Ringold GM (1985) A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia. Science 229(4716):867–869

    CAS  PubMed  Google Scholar 

  147. Beutler B, Milsark IW, Cerami AC (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229(4716):869–871

    CAS  PubMed  Google Scholar 

  148. Murphy M, Perussia B, Trinchieri G (1988) Effects of recombinant tumor necrosis factor, lymphotoxin, and immune interferon on proliferation and differentiation of enriched hematopoietic precursor cells. Exp Hematol 16(2):131–138

    CAS  PubMed  Google Scholar 

  149. Dayer JM, Beutler B, Cerami A (1985) Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J Exp Med 162(6):2163–2168

    CAS  PubMed  Google Scholar 

  150. Mariani TJ, Sandefur S, Roby JD, Pierce RA (1998) Collagenase-3 induction in rat lung fibroblasts requires the combined effects of tumor necrosis factor-alpha and 12-lipoxygenase metabolites: a model of macrophage-induced, fibroblast-driven extracellular matrix remodeling during inflammatory lung injury. Mol Biol Cell 9(6):1411–1424

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Salvo P, Dini V, Di Francesco F, Romanelli M (2015) The role of biomedical sensors in wound healing. Wound Medicine 8:15–18

    Google Scholar 

  152. Werner S, Grose R (2003) Regulation of wound healing by growth factors and cytokines. Physiol Rev 83(3):835–870

    CAS  PubMed  Google Scholar 

  153. Heldin CH, Eriksson U, Ostman A (2002) New members of the platelet-derived growth factor family of mitogens. Arch Biochem Biophys 398(2):284–290

    CAS  PubMed  Google Scholar 

  154. Barrandon Y, Green H (1987) Cell migration is essential for sustained growth of keratinocyte colonies: the roles of transforming growth factor-alpha and epidermal growth factor. Cell 50(7):1131–1137

    CAS  PubMed  Google Scholar 

  155. Li G, Gustafson-Brown C, Hanks SK, Nason K, Arbeit JM, Pogliano K, Wisdom RM, Johnson RS (2003) c-Jun is essential for organization of the epidermal leading edge. Dev Cell 4(6):865–877

    CAS  PubMed  Google Scholar 

  156. Sano S, Itami S, Takeda K, Tarutani M, Yamaguchi Y, Miura H, Yoshikawa K, Akira S, Takeda J (1999) Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis. EMBO J 18(17):4657–4668

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Brem H, Stojadinovic O, Diegelmann RF, Entero H, Lee B, Pastar I, Golinko M, Rosenberg H, Tomic-Canic M (2007) Molecular markers in patients with chronic wounds to guide surgical debridement. Mol Med 13(1–2):30–39

    PubMed  PubMed Central  Google Scholar 

  158. Powers CJ, McLeskey SW, Wellstein A (2000) Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer 7(3):165–197

    CAS  PubMed  Google Scholar 

  159. Borena BM, Martens A, Broeckx SY, Meyer E, Chiers K, Duchateau L, Spaas JH (2015) Regenerative Skin Wound Healing in Mammals: State-of-the-Art on Growth Factor and Stem Cell Based Treatments. Cell Physiol Biochem 36(1):1–23

    CAS  PubMed  Google Scholar 

  160. Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H (2009) The role of vascular endothelial growth factor in wound healing. J Surg Res 153(2):347–358

    CAS  PubMed  Google Scholar 

  161. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M (2008) Growth factors and cytokines in wound healing. Wound Repair Regen 16(5):585–601

    PubMed  Google Scholar 

  162. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH et al (1986) Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A 83(12):4167–4171

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Klass BR, Grobbelaar AO, Rolfe KJ (2009) Transforming growth factor beta1 signalling, wound healing and repair: a multifunctional cytokine with clinical implications for wound repair, a delicate balance. Postgrad Med J 85(999):9–14

    CAS  PubMed  Google Scholar 

  164. Chesnoy S, Lee PY, Huang L (2003) Intradermal injection of transforming growth factor-beta1 gene enhances wound healing in genetically diabetic mice. Pharm Res 20(3):345–350

    CAS  PubMed  Google Scholar 

  165. Gailit J, Welch MP, Clark RA (1994) TGF-beta 1 stimulates expression of keratinocyte integrins during re-epithelialization of cutaneous wounds. J Invest Dermatol 103(2):221–227

    CAS  PubMed  Google Scholar 

  166. Amendt C, Mann A, Schirmacher P, Blessing M (2002) Resistance of keratinocytes to TGFβ-mediated growth restriction and apoptosis induction accelerates re-epithelialization in skin wounds. J Cell Sci 115(10):2189–2198

    CAS  PubMed  Google Scholar 

  167. Ashcroft GS, Yang X, Glick AB, Weinstein M, Letterio JL, Mizel DE, Anzano M, Greenwell-Wild T, Wahl SM, Deng C, Roberts AB (1999) Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1(5):260–266

    CAS  PubMed  Google Scholar 

  168. Lamar JM, Iyer V, DiPersio CM (2008) Integrin alpha3beta1 potentiates TGFbeta-mediated induction of MMP-9 in immortalized keratinocytes. J Invest Dermatol 128(3):575–586

    CAS  PubMed  Google Scholar 

  169. Rees PA, Greaves NS, Baguneid M, Bayat A (2015) Chemokines in wound healing and as potential therapeutic targets for reducing cutaneous scarring. Adv Wound Care (New Rochelle) 4(11):687–703

    Google Scholar 

  170. Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, Dzuiba J, Van Damme J, Walz A, Marriott D, Chan S-Y, Roczniak S, Shanafelt AB (1995) The Functional Role of the ELR Motif in CXC Chemokine-mediated Angiogenesis. J Biol Chem 270(45):27348–27357

    CAS  PubMed  Google Scholar 

  171. Strieter RM, Burdick MD, Gomperts BN, Belperio JA, Keane MP (2005) CXC chemokines in angiogenesis. Cytokine Growth Factor Rev 16(6):593–609

    CAS  PubMed  Google Scholar 

  172. McCarty SM, Percival SL (2013) Proteases and Delayed Wound Healing. Adv Wound Care (New Rochelle). 2(8):438–447

    PubMed  PubMed Central  Google Scholar 

  173. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8(3):221–233

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Ravanti L, Kahari VM (2000) Matrix metalloproteinases in wound repair (review). Int J Mol Med 6(4):391–407

    CAS  PubMed  Google Scholar 

  175. Midwood KS, Williams LV, Schwarzbauer JE (2004) Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol 36(6):1031–1037

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pornanong Aramwit Pharm.D., Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Angspatt, A., Puttilerpong, C., Sirithanakorn, C., Aramwit, P. (2018). Traditional and Nontraditional Evaluation of Wound Healing Process. In: Shiffman, M., Low, M. (eds) Chronic Wounds, Wound Dressings and Wound Healing. Recent Clinical Techniques, Results, and Research in Wounds, vol 6. Springer, Cham. https://doi.org/10.1007/15695_2017_106

Download citation

  • DOI: https://doi.org/10.1007/15695_2017_106

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-10697-3

  • Online ISBN: 978-3-030-10698-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics