Surgery pp 191-208 | Cite as

Wounds: Biology, Pathology, and Management

  • H. Peter Lorenz
  • Michael T. Longaker


Wound healing is an orchestrated biological process initiated by tissue injury and culminating in restoration of tissue integrity. The end result of the repair process is fibrosis and scar in all organ systems except bone and except for specialized conditions of liver injury. Because surgeons induce tissue injury, a thorough understanding of the wound repair process is fundamental to the practice of surgery; thus, surgeons and wound repair have enjoyed a close relationship from the beginning of surgery.


Vascular Endothelial Growth Factor Wound Healing Wound Site Wound Repair Hypertrophic Scar 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ginsberg MH, Du X, Plow EF. Inside-out integrin signalling. Curr Opin Cell Biol 1992;4:766–771.PubMedGoogle Scholar
  2. 2.
    Roberts HR, Tabares AH. Overview of the coagulation reactions. In: High KA, Roberts HR, eds. Molecular Basis of Thrombosis and Hemostasis. New York: Marcel Dekker, 1995:35–50.Google Scholar
  3. 3.
    Clark RAF. Wound repair. Overview and general considerations. In: Clark RAF, ed. The Molecular and Cellular Biology of Wound Repair, 2nd ed. New York: Plenum Press, 1996:3–50.Google Scholar
  4. 4.
    DiPietro LA. Wound healing: the role of the macrophage and other immune cells. Shock 1995;4:233–240.PubMedGoogle Scholar
  5. 5.
    Leibovich SJ, Ross R. The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol 1975;78:71–100.PubMedGoogle Scholar
  6. 6.
    Chesney J, Bucala R. Peripheral blood fibrocytes: mesenchymal precursor cells and the pathogenesis of fibrosis. Curr Rheumatol Rep 2000;2:501–505.PubMedGoogle Scholar
  7. 7.
    Fathke C, Wilson L, Hutter J, et al. Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair. Stem Cells 2004;22:812–822.PubMedGoogle Scholar
  8. 8.
    Kataoka K, Medina RJ, Kageyama T, et al. Participation of adult mouse bone marrow cells in reconstitution of skin. Am J Pathol 2003;163:1227–1231.PubMedGoogle Scholar
  9. 9.
    Miller EJ, Gay S. Collagen structure and function. In: Cohen IK, Diegelmann RF, Lindblad WJ, eds. Wound Healing. Biochemical and Clinical Aspects. Philadelphia: W. B. Saunders Company, 1992:130–151.Google Scholar
  10. 10.
    Lodish H, Baltimore D, Berk A, Zipursky SL, Matsudaira P, Darnell J. Multicellularity: cell-cell and cell-matrix interactions. In: Molecular Cell Biology, 4th ed. New York: Scientific American Books, Inc., 1995:1123–1200.Google Scholar
  11. 11.
    Koch M, Schulze J, Hansen U, et al. A novel marker of tissue junctions, collagen XXII. J Biol Chem 2004;279:22514–22521.PubMedGoogle Scholar
  12. 12.
    Boot-Handford RP, Tuckwell DS, Plumb DA, Rock CF, Poulsom R. A novel and highly conserved collagen (pro(alpha) 1 (XXVII)) with a unique expression pattern and unusual molecular characteristics establishes a new clade within the vertebrate fibrillar collagen family. J Biol Chem 2003;278:31067–31077.PubMedGoogle Scholar
  13. 13.
    Marinkovich MP, Keene DR, Rimberg CS, Burgeson RE. Cellular origin of the dermal-epidermal basement membrane. Dev Dyn 1993;197:255–267.PubMedGoogle Scholar
  14. 14.
    Kobayashi H, Ishii M, Chanoki M, et al. Immunohistochemical localization of lysyl oxidase in normal human skin. Br J Dermatol 1994;131:325–330.PubMedGoogle Scholar
  15. 15.
    Pierce GF, Vande Berg J, Rudolph R, Tarpley J, Mustoe TA. Platelet-derived growth factor-BB and transforming growth factor beta 1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds. Am J Pathol 1991;138:629–646.PubMedGoogle Scholar
  16. 16.
    Gabbiani G. Evolution and clinical implications of the myofibroblast concept. Cardiovasc Res 1998;38:545–548.PubMedGoogle Scholar
  17. 17.
    Woodley DT. Reepithelialization. In: Clark RAF, ed. The Molecular and Cellular Biology of Wound Repair. New York: Plenum Press, 1996:339–350.Google Scholar
  18. 18.
    Moses MA, Marikovsky M, Harper JW, et al. Temporal study of the activity of matrix metalloproteinases and their endogenous inhibitors during wound healing. J Cell Biochem 1996;60:379–386.PubMedGoogle Scholar
  19. 19.
    Talhouk RS, Bissell MJ, Werb Z. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol 1992;118:1271–1282.PubMedGoogle Scholar
  20. 20.
    Witte MB, Thornton FJ, Kiyama T, et al. Metalloproteinase inhibitors and wound healing: a novel enhancer of wound strength. Surgery 1998;124:464–470.PubMedGoogle Scholar
  21. 21.
    Levenson SM, Geever EF, Crowley LV, Oates JF, Berard CW, Rosen H. The healing of rat skin wounds. Ann Surg 1965;161:293–308.PubMedGoogle Scholar
  22. 22.
    Pierce GF, Brown D, Mustoe TA. Quantitative analysis of inflammatory cell influx, procollagen type I synthesis, and collagen cross-linking in incisional wounds: influence of PDGF-BB and TGF-beta 1 therapy. J Lab Clin Med 1991;117:373–382.PubMedGoogle Scholar
  23. 23.
    Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A. Role of platelet-derived growth factor in wound healing. J Cell Biochem 1991;45:319–326.PubMedGoogle Scholar
  24. 24.
    Cromack DT, Pierce GF, Mustoe TA. TGF-beta and PDGF mediated tissue repair: identifying mechanisms of action using impaired and normal models of wound healing. Prog Clin Biol Res 1991;365:359–373.PubMedGoogle Scholar
  25. 25.
    Roberts AB. Molecular and cell biology of TGF-beta. Miner Electrolyte Metab 1998;24:111–119.PubMedGoogle Scholar
  26. 26.
    Roberts AB, Sporn MB. Transforming growth factor-β. In: Clark RAF, ed. The Molecular and Cellular Biology of Wound Repair. New York: Plenum Press, 1996:275–308.Google Scholar
  27. 27.
    Mustoe TA, Pierce GF, Morishima C, Deuel TF. Growth factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model. J Clin Invest 1991;87:694–703.PubMedGoogle Scholar
  28. 28.
    Nissen NN, Polverini PJ, Koch AE, Volin MV, Gamelli RL, DiPietro LA. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 1998;152:1445–1452.PubMedGoogle Scholar
  29. 29.
    Banks RE, Forbes MA, Kinsey SE, et al. Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. Br J Cancer 1998;77:956–964.PubMedGoogle Scholar
  30. 30.
    Frank S, Hubner G, Breier G, Longaker MT, Greenhalgh DG, Werner S. Regulation of vascular endothelial growth factor expression in cultured keratinocytes. Implications for normal and impaired wound healing. J Biol Chem 1995;270:12607–12613.PubMedGoogle Scholar
  31. 31.
    Werner S, Smola H, Liao X, et al. The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science 1994;266:819–822.PubMedGoogle Scholar
  32. 32.
    Han DS, Li F, Holt L, et al. Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats. Am J Physiol Gastrointest Liver Physiol 2000;279:G1011–G1022.PubMedGoogle Scholar
  33. 33.
    Robertson JG, Pickering KJ, Belford DA. Insulin-like growth factor I (IGF-I) and IGF-binding proteins in rat wound fluid. Endocrinology 1996;137:2774–2781.PubMedGoogle Scholar
  34. 34.
    Heino J, Heinonen T. Interleukin-1 beta prevents the stimulatory effect of transforming growth factor-beta on collagen gene expression in human skin fibroblasts. Biochem J 1990;271:827–830.PubMedGoogle Scholar
  35. 35.
    Cromack DT, Porras-Reyes B, Purdy JA, Pierce GF, Mustoe TA. Acceleration of tissue repair by transforming growth factor beta 1: identification of in vivo mechanism of action with radiotherapy-induced specific healing deficits. Surgery 1993;113:36–42.PubMedGoogle Scholar
  36. 36.
    Giannobile WV, Hernandez RA, Finkelman RD, et al. Comparative effects of platelet-derived growth factor-BB and insulin-like growth factor-I, individually and in combination, on periodontal regeneration in Macaca fascicularis. J Periodont Res 1996;31:301–312.PubMedGoogle Scholar
  37. 37.
    Suh DY, Hunt TK, Spencer EM. Insulin-like growth factor-I reverses the impairment of wound healing induced by corticosteroids in rats. Endocrinology 1992;131:2399–2403.PubMedGoogle Scholar
  38. 38.
    Tanaka E, Ase K, Okuda T, Okumura M, Nogimori K. Mechanism of acceleration of wound healing by basic fibroblast growth factor in genetically diabetic mice. Biol Pharm Bull 1996;19:1141–1148.PubMedGoogle Scholar
  39. 39.
    Bitar MS. Insulin-like growth factor-1 reverses diabetes-induced wound healing impairment in rats. Horm Metab Res 1997;29:383–386.PubMedGoogle Scholar
  40. 40.
    Greenhalgh DG, Sprugel KH, Murray MJ, Ross R. PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am J Pathol 1990;136:1235–1246.PubMedGoogle Scholar
  41. 41.
    Wu L, Brucker M, Gruskin E, Roth SI, Mustoe TA. Differential effects of platelet-derived growth factor BB in accelerating wound healing in aged versus young animals: the impact of tissue hypoxia. Plast Reconstr Surg 1997;99:815–822;discussion 823–824.PubMedGoogle Scholar
  42. 42.
    Slavin J, Nash JR, Kingsnorth AN. Effect of transforming growth factor beta and basic fibroblast growth factor on steroid-impaired healing intestinal wounds. Br J Surg 1992;79:69–72.PubMedGoogle Scholar
  43. 43.
    Albertson S, Hummel RPD, Breeden M, Greenhalgh DG. PDGF and FGF reverse the healing impairment in protein-malnourished diabetic mice. Surgery 1993;114:368–372;discussion 372–373.PubMedGoogle Scholar
  44. 44.
    Abe M, Oda N, Sato Y. Cell-associated activation of latent transforming growth factor-beta by calpain. J Cell Physiol 1998;174:186–193.PubMedGoogle Scholar
  45. 45.
    Burmester JK, Qian SW, Ohlsen D, Phan S, Sporn MB, Roberts AB. Mutational analysis of a transforming growth factor-beta receptor binding site. Growth Factors 1998;15:231–242.PubMedGoogle Scholar
  46. 46.
    Gold LI, Sung JJ, Siebert JW, Longaker MT. Type I (RI) and type II (RE) receptors for transforming growth factor-beta isoforms are expressed subsequent to transforming growth factor-beta ligands during excisional wound repair. Am J Pathol 1997;150:209–222.PubMedGoogle Scholar
  47. 47.
    Ferguson MW, Whitby DJ, Shah M, Armstrong J, Siebert JW, Longaker MT. Scar formation: the spectral nature of fetal and adult wound repair. Plast Reconstr Surg 1996;97:854–860.PubMedGoogle Scholar
  48. 48.
    Beanes SR, Hu FY, Soo C, et al. Confocal microscopic analysis of scarless repair in the fetal rat: defining the transition. Plast Reconstr Surg 2002;109:160–170.PubMedGoogle Scholar
  49. 49.
    Cass DL, Bullard KM, Sylvester KG, Yang EY, Longaker MT, Adzick NS. Wound size and gestational age modulate scar formation in fetal wound repair. J Pediatr Surg 1997;32:411–415.PubMedGoogle Scholar
  50. 50.
    Longaker MT, Whitby DJ, Adzick NS, et al. Studies in fetal wound healing, VI. Second and early third trimester fetal wounds demonstrate rapid collagen deposition without scar formation. J Pediatr Surg 1990;25:63–68;discussion 68–69.PubMedGoogle Scholar
  51. 51.
    Lorenz HP, Whitby DJ, Longaker MT, Adzick NS. Fetal wound healing. The ontogeny of scar formation in the non-human primate. Ann Surg 1993;217:391–396.PubMedGoogle Scholar
  52. 52.
    Lorenz HP, Lin RY, Longaker MT, Whitby DJ, Adzick NS. The fetal fibroblast: the effector cell of scarless fetal skin repair. Plast Reconstr Surg 1995;96:1251–1259;discussion 1260–1261.PubMedGoogle Scholar
  53. 53.
    Lorenz HP, Longaker MT, Perkocha LA, Jennings RW, Harrison MR, Adzick NS. Scarless wound repair: a human fetal skin model. Development 1992;114:253–259.PubMedGoogle Scholar
  54. 54.
    Soo C, Beanes SR, Hu FY, et al. Ontogenetic transition in fetal wound transforming growth factor-beta regulation correlates with collagen organization. Am J Pathol 2003;163:2459–2476.PubMedGoogle Scholar
  55. 55.
    Shah M, Foreman DM, Ferguson MW. Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents. J Cell Sci 1994;107:1137–1157.PubMedGoogle Scholar
  56. 56.
    Ashcroft GS, Yang X, Glick AB, et al. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response [see comments]. Nature Cell Biol 1999;1:260–266.PubMedGoogle Scholar
  57. 57.
    Young T. Pressure sores: incidence, risk assessment and prevention. Br J Nurs 1997;6:319–322.PubMedGoogle Scholar
  58. 58.
    Schubert V, Perbeck L, Schubert PA. Skin microcirculatory and thermal changes in elderly subjects with early stage of pressure sores. Clin Physiol 1994;14:1–13.PubMedGoogle Scholar
  59. 59.
    Relander M, Palmer B. Recurrence of surgically treated pressure sores. Scan J Plast Reconstr Surg Hand Surg 1988;22:89–92.Google Scholar
  60. 60.
    Kierney PC, Engrav LH, Isik FF, Esselman PC, Cardenas DD, Rand RP. Results of 268 pressure sores in 158 patients managed jointly by plastic surgery and rehabilitation medicine. Plast Reconstr Surg 1998;102:765–772.PubMedGoogle Scholar
  61. 61.
    Burton CS. Venous ulcers. Am J Surg 1994;167:37S–40S;discussion 40S–41S.PubMedGoogle Scholar
  62. 62.
    Margolis DJ, Cohen JH. Management of chronic venous leg ulcers: a literature-guided approach. Clin Dermatol 1994;12:19–26.PubMedGoogle Scholar
  63. 63.
    Padberg FT, Back TL, Thompson PN, Hobson RW 2nd. Transcutaneous oxygen (TcPo2) estimates probability of healing in the ischemic extremity. J Surg Res 1996;60:365–369.PubMedGoogle Scholar
  64. 64.
    Bernstein EF, Harisiadis L, Salomon GD, et al. Healing impairment of open wounds by skin irradiation. J Derm Surg Oncol 1994;20:757–760.Google Scholar
  65. 65.
    Robson MC. Infection in the surgical patient: an imbalance in the normal equilibrium. Clin Plast Surg 1979;6:493–503.PubMedGoogle Scholar
  66. 66.
    Robson MC. Wound infection. A failure of wound healing caused by an imbalance of bacteria. Surg Clin North Am 1997;77:637–650.PubMedGoogle Scholar
  67. 67.
    Robson MC, Stenberg BD, Heggers JP. Wound healing alterations caused by infection. Clin Plast Surg 1990;17:485–492.PubMedGoogle Scholar
  68. 68.
    Robson MC, Krizek TJ. Predicting skin graft survival. J Trauma 1973;13:213–217.PubMedGoogle Scholar
  69. 69.
    Murphy RC, Robson MC, Heggers JP, Kadowaki M. The effect of microbial contamination on musculocutaneous and random flaps. J Surg Res 1986;41:75–80.PubMedGoogle Scholar
  70. 70.
    Barbul A, Purtill WA. Nutrition in wound healing. Clin Dermatol 1994;12:133–140.PubMedGoogle Scholar
  71. 71.
    Muller MJ, Herndon DN. The challenge of burns. Lancet 1994;343:216–220.PubMedGoogle Scholar
  72. 72.
    Albina JE. Nutrition and wound healing. J Parenter Enteral Nutr 1994;18:367–376.Google Scholar
  73. 73.
    Thompson WD, Ravdin IS, Frank IL. Effect of hypoproteinemia on wound disruption. Arch Surg 1938;26:500–508.Google Scholar
  74. 74.
    Modolin M, Bevilacqua RG, Margarido NF, Lima-Goncalves E. Effects of protein depletion and repletion on experimental open wound contraction. Ann Plast Surg 1985;15:123–126.PubMedGoogle Scholar
  75. 75.
    Levenson SM, Demetriou AA. Metabolic factors. In: Cohen IK, Diegelmann RF, Lindblad WJ, eds. Wound Healing, Biochemical and Clinical Aspects. Philadelphia: W. B. Saunders Company, 1992:248–273.Google Scholar
  76. 76.
    Alcain FJ, Buron MI. Ascorbate on cell growth and differentiation. J Bioenerg Biomembr 1994;26:393–398.PubMedGoogle Scholar
  77. 77.
    Ehrlich HP, Hunt TK. Effects of cortisone and vitamin A on wound healing. Ann Surg 1968;167:324–328.PubMedGoogle Scholar
  78. 78.
    Ehrlich HP, Tarver H, Hunt TK. Effects of vitamin A and glucocorticoids upon inflammation and collagen synthesis. Ann Surg 1973;177:222–227.PubMedGoogle Scholar
  79. 79.
    Masse PG, Pritzker KP, Mendes MG, Boskey AL, Weiser H. Vitamin B6 deficiency experimentally-induced bone and joint disorder: microscopic, radiographic and biochemical evidence. Br J Nutr 1994;71:919–932.PubMedGoogle Scholar
  80. 80.
    La Van FB, Hunt TK. Oxygen and wound healing. Clin Plast Surg 1990;17:463–472.Google Scholar
  81. 81.
    Allen DB, Maguire JJ, Mahdavian M, et al. Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg 1997;132:991–996.PubMedGoogle Scholar
  82. 82.
    Hopf HW, Hunt TK, West JM, et al. Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg 1997;132:997–1004;discussion 1005.PubMedGoogle Scholar
  83. 83.
    Jonsson K, Jensen JA, Goodson WH, et al. Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients. Ann Surg 1991;214:605–613.PubMedGoogle Scholar
  84. 84.
    Hunt TK, Pai MP. The effect of varying ambient oxygen tensions on wound metabolism and collagen synthesis. Surg Gynecol Obstet 1972;135:561–567.PubMedGoogle Scholar
  85. 85.
    Uhl E, Sirsjo A, Haapaniemi T, Nilsson G, Nylander G. Hyperbaric oxygen improves wound healing in normal and ischemic skin tissue. Plast Reconstr Surg 1994;93:835–841.PubMedGoogle Scholar
  86. 86.
    Werner S, Breeden M, Hubner G, Greenhalgh DG, Longaker MT. Induction of keratinocyte growth factor expression is reduced and delayed during wound healing in the genetically diabetic mouse. J Invest Dermatol 1994;103:469–473.PubMedGoogle Scholar
  87. 87.
    Beer HD, Longaker MT, Werner S. Reduced expression of PDGF and PDGF receptors during impaired wound healing. J Invest Dermatol 1997;109:132–138.PubMedGoogle Scholar
  88. 88.
    Goodson WH, Hunt TK. Wound healing in experimental diabetes mellitus: importance of early insulin therapy. Surg Forum 1978;29:95–98.PubMedGoogle Scholar
  89. 89.
    Goodson WH, Hunt TK. Deficient collagen formation by obese mice in a standard wound model. Am J Surg 1979;138:692–694.PubMedGoogle Scholar
  90. 90.
    Ehrlich HP, Hunt TK. The effects of cortisone and anabolic steroids on the tensile strength of healing wounds. Ann Surg 1969;170:203–206.PubMedGoogle Scholar
  91. 91.
    Marks JG Jr, Cano C, Leitzel K, Lipton A. Inhibition of wound healing by topical steroids. J Derm Surg Oncol 1983;9:819–821.Google Scholar
  92. 92.
    Brauchle M, Fassler R, Werner S. Suppression of keratinocyte growth factor expression by glucocorticoids in vitro and during wound healing. J Invest Dermatol 1995;105:579–584.PubMedGoogle Scholar
  93. 93.
    Schwentker A, Evans SM, Partington M, Johnson BL, Koch CJ, Thom SR. A model of wound healing in chronically radiation-damaged rat skin. Cancer Lett 1998;128:71–78.PubMedGoogle Scholar
  94. 94.
    Zhao LL, Davidson JD, Wee SC, Roth SI, Mustoe TA. Effect of hyperbaric oxygen and growth factors on rabbit ear ischemic ulcers. Arch Surg 1994;129:1043–1049.PubMedGoogle Scholar
  95. 95.
    Drake DB, Oishi SN. Wound healing considerations in chemotherapy and radiation therapy. Clin Plast Surg 1995;22:31–37.PubMedGoogle Scholar
  96. 96.
    Tredget EE, Nedelec B, Scott PG, Ghahary A. Hypertrophic scars, keloids, and contractures. The cellular and molecular basis for therapy. Surg Clin North Am 1997;77:701–730.PubMedGoogle Scholar
  97. 97.
    Yang GP, Lim IJ, Phan TT, Lorenz HP, Longaker MT. From scarless fetal wounds to keloids: molecular studies in wound healing. Wound Repair Regen 2003;11:411–18.PubMedGoogle Scholar
  98. 98.
    Wassermann RJ, Polo M, Smith P, Wang X, Ko F, Robson MC. Differential production of apoptosis-modulating proteins in patients with hypertrophic burn scar. J Surg Res 1998;75:74–80.PubMedGoogle Scholar
  99. 99.
    Blackburn WR, Cosman B. Histologic basis of keloid and hypertrophic scar differentiation. Clinicopathologic correlation. Arch Pathol 1966;82:65–71.PubMedGoogle Scholar
  100. 100.
    Kischer CW, Shetlar MR, Chvapil M. Hypertrophic scars and keloids: a review and new concept concerning their origin. Scan Electron Microsc 1982 (pt 4):1699–1713.Google Scholar
  101. 101.
    Scott PG, Dodd CM, Ghahary A, Shen YJ, Tredget EE. Fibroblasts from post-burn hypertrophic scar tissue synthesize less decorin than normal dermal fibroblasts. Clin Sci 1998;94:541–547.PubMedGoogle Scholar
  102. 102.
    Bettinger DA, Yager DR, Diegelmann RF, Cohen IK. The effect of TGF-beta on keloid fibroblast proliferation and collagen synthesis. Plast Reconstr Surg 1996;98:827–833.PubMedGoogle Scholar
  103. 103.
    Younai S, Nichter LS, Wellisz T, Reinisch J, Nimni ME, Tuan TL. Modulation of collagen synthesis by transforming growth factor-beta in keloid and hypertrophic scar fibroblasts. Ann Plast Surg 1994;33:148–151.PubMedGoogle Scholar
  104. 104.
    Mustoe TA, Cooter RD, Gold MH, et al. International clinical recommendations on scar management. Plast Reconstr Surg 2002;110:560–571.PubMedGoogle Scholar
  105. 105.
    Alster T. Laser scar revision: comparison study of 585-nm pulsed dye laser with and without intralesional corticosteroids. Dermatol Surg 2003;29:25–29.PubMedGoogle Scholar
  106. 106.
    Murray JC. Keloids and hypertrophic scars. Clin Dermatol 1994;12:27–37.PubMedGoogle Scholar
  107. 107.
    Appleton I, Brown NJ, Willoughby DA. Apoptosis, necrosis, and proliferation: possible implications in the etiology of keloids. Am J Pathol 1996;149:1441–1447.PubMedGoogle Scholar
  108. 108.
    Sayah DN, Shaw WW, Holmes EC, et al. Downregulation of apoptosis genes accounts for aberrant cellular growth in keloid tissue. Surg Forum 1998;49:596–598.Google Scholar
  109. 109.
    Tuan TL, Nichter LS. The molecular basis of keloid and hypertrophic scar formation. Mol Med Today 1998;4:19–24.PubMedGoogle Scholar
  110. 110.
    Kikuchi K, Kadono T, Takehara K. Effects of various growth factors and histamine on cultured keloid fibroblasts. Dermatology 1995;190:4–8.PubMedGoogle Scholar
  111. 111.
    Lim IJ, Phan TT, Song C, Tan WT, Longaker MT. Investigation of the influence of keloid-derived keratinocytes of fibroblast growth and proliferation in vitro. Plast Reconstr Surg 2001;107:797–808.PubMedGoogle Scholar
  112. 112.
    Maguire HC. Treatment of keloids with triamcinolone acetonide injected intralesionally. JAMA 1965;192:325–327.PubMedGoogle Scholar
  113. 113.
    Kauh YC, Rouda S, Mondragon G, et al. Major suppression of pro-alphal(I) type I collagen gene expression in the dermis after keloid excision and immediate intrawound injection of triamcinolone acetonide. J Am Acad Dermatol 1997;37:586–589.PubMedGoogle Scholar
  114. 114.
    Klumpar DI, Murray JC, Anscher M. Keloids treated with excision followed by radiation therapy. J Am Acad Dermatol 1994;31(2 pt 1):225–231.PubMedGoogle Scholar
  115. 115.
    Minkowitz F. Regression of massive keloid following partial excision and post-operative intralesional administration of triamcinolone. Br J Plast Surg 1967;20:432–435.PubMedGoogle Scholar
  116. 116.
    Griffith BH, Monroe CW, McKinney P. A follow-up study on the treatment of keloids with triamcinolone acetonide. Plast Reconstr Surg 1970;46:145–150.PubMedGoogle Scholar
  117. 117.
    Lee SM, Ngim CK, Chan YY, Ho MJ. A comparison of Sil-K and Epiderm in scar management. Burns 1996;22:483–487.PubMedGoogle Scholar
  118. 118.
    Palmieri B, Gozzi G, Palmieri G. Vitamin E added silicone gel sheets for treatment of hypertrophic scars and keloids. Int J Dermatol 1995;34:506–509.PubMedGoogle Scholar
  119. 119.
    Kelly AP. Medical and surgical therapies for keloids. Dermatol Ther 2004;17:212–218.PubMedGoogle Scholar
  120. 120.
    Berman B, Villa A. Imiquimod 5% cream for keloid management. Dermatol Surg 2003;29:1050–1051.PubMedGoogle Scholar
  121. 121.
    Chau D, Mancoll JS, Lee S, et al. Tamoxifen downregulates TGF-beta production in keloid fibroblasts. Ann Plast Surg 1998;40:490–493.PubMedGoogle Scholar
  122. 122.
    Mancoll JS, Chau D, Munger J, et al. Tamoxifen downregulates TGF-β production by keloid fibroblasts. Surg Forum 1997;48:133–137.Google Scholar
  123. 123.
    Otani Y, Tabata Y, Ikada Y. A new biological glue from gelatin and poly (L-glutamic acid). J Biomed Mater Res 1996;31:158–166.PubMedGoogle Scholar
  124. 124.
    DeBono R. A simple, inexpensive method for precise application of cyanoacrylate tissue adhesive. Plast Reconstr Surg 1997;100:447–450.PubMedGoogle Scholar
  125. 125.
    Breuing K, Eriksson E, Liu P, Miller DR. Healing of partial thickness porcine skin wounds in a liquid environment. J Surg Res 1992;52:50–58.PubMedGoogle Scholar
  126. 126.
    Svensjo T, Pomahac B, Yao F, Slama J, Eriksson E. Accelerated healing of full-thickness skin wounds in a wet environment. Plast Reconstr Surg 2000;106:602–612; discussion 613–614.PubMedGoogle Scholar
  127. 127.
    Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg 1997;38:563–576; discussion 577.PubMedGoogle Scholar
  128. 128.
    Genecov DG, Schneider AM, Morykwas MJ, Parker D, White WL, Argenta LC. A controlled subatmospheric pressure dressing increases the rate of skin graft donor site reepithelialization. Ann Plast Surg 1998;40:219–225.PubMedGoogle Scholar
  129. 129.
    Richard JL, Parer RC, Daures JP, et al. Effect of topical basic fibroblast growth factor on the healing of chronic diabetic neuropathic ulcer of the foot. A pilot, randomized, double-blind, placebo-controlled study. Diabetes Care 1995;18:64–69.PubMedGoogle Scholar
  130. 130.
    Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group. J Vasc Surg 1995;21:71–78; discussion 79–81.PubMedGoogle Scholar
  131. 131.
    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;183:61–64.PubMedGoogle Scholar
  132. 132.
    Pierce GF, Tarpley JE, Allman RM, et al. Tissue repair processes in healing chronic pressure ulcers treated with recombinant platelet-derived growth factor BB. Am J Pathol 1994;145:1399–1410.PubMedGoogle Scholar
  133. 133.
    Jones SC, Curtsinger LJ, Whalen JD, et al. Effect of topical recombinant TGF-beta on healing of partial thickness injuries. J Surg Res 1991;51:344–352.PubMedGoogle Scholar
  134. 134.
    Bullen EC, Longaker MT, Updike DL, et al. Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds. J Invest Dermatol 1995;104:236–240.PubMedGoogle Scholar
  135. 135.
    Feedar JA. Clinical management of chronic wounds. In: McCulloch JM, Kloth LC, Feedar JA, eds. Wound Healing Alternatives in Management. Philadelphia: F. A. Davis Company, 1995:137–185.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • H. Peter Lorenz
    • 1
    • 2
  • Michael T. Longaker
    • 1
    • 2
  1. 1.Department of Surgery (Plastic and Reconstructive)Stanford University School of MedicineStanfordUSA
  2. 2.Children’s Surgical Research ProgramStanford University School of MedicineStanfordUSA

Personalised recommendations