A Primer on Wound Healing in Colorectal Surgery in the Age of Bioprosthetic Materials

 

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Abstract

Wound healing is a complex, dynamic process that is vital for closure of cutaneous injuries, restoration of abdominal wall integrity after laparotomy closure, and to prevent anastomotic dehiscence after bowel surgery. Derangements in healing have been described in multiple processes including diabetes mellitus, corticosteroid use, irradiation for malignancy, and inflammatory bowel disease. A thorough understanding of the process of healing is necessary for clinical decision making and knowledge of the current state of the science may lead future researchers in developing methods to enable our ability to modulate healing, ultimately improving outcomes. An exciting example of this ability is the use of bioprosthetic materials used for abdominal wall surgery (hernia repair/reconstruction). These bioprosthetic meshes are able to regenerate and remodel from an allograft or xenograft collagen matrix into site-specific tissue; ultimately being degraded and minimizing the risk of long-term complications seen with synthetic materials. The purpose of this article is to review healing as it relates to cutaneous and intestinal trauma and surgery, factors that impact wound healing, and wound healing as it pertains to bioprosthetic materials.

• References

• 1 Singer AJ, Clark RAF. Cutaneous wound healing. N Engl J Med 1999; 341 (10) 738-746
  CrossrefPubMedGoogle Scholar
• 2 Schäffer M, Barbul A. Lymphocyte function in wound healing and following injury. Br J Surg 1998; 85 (4) 444-460
  CrossrefPubMedGoogle Scholar
• 3 Ross R, Everett NB, Tyler R. Wound healing and collagen formation. VI. The origin of the wound fibroblast studied in parabiosis. J Cell Biol 1970; 44 (3) 645-654
  CrossrefPubMedGoogle Scholar
• 4 Esmon CT. Cell mediated events that control blood coagulation and vascular injury. Annu Rev Cell Biol 1993; 9: 1-26
  CrossrefPubMedGoogle Scholar
• 5 Stiernberg J, Redin WR, Warner WS, Carney DH. The role of thrombin and thrombin receptor activating peptide (TRAP-508) in initiation of tissue repair. Thromb Haemost 1993; 70 (1) 158-162
  PubMedGoogle Scholar
• 6 Magnusson MK, Mosher DF. Fibronectin: structure, assembly, and cardiovascular implications. Arterioscler Thromb Vasc Biol 1998; 18 (9) 1363-1370
  CrossrefPubMedGoogle Scholar
• 7 Chen H, Mosher DF. Formation of sodium dodecyl sulfatestable fibronectin multimers. Failure to detect products of hioldisulfide exchange in cyanogen bromide or limited acid digests of stabilized matrix fibronectin. J Biol Chem 1996; 271 (15) 9084-9089
  CrossrefPubMedGoogle Scholar
• 8 Bowditch RD, Hariharan M, Tominna EF , et al. Identification of a novel integrin binding site in fibronectin. Differential utilization by beta 3 integrins. J Biol Chem 1994; 269 (14) 10856-10863
  PubMedGoogle Scholar
• 9 Mast BA, Schultz GS. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair Regen 1996; 4 (4) 411-420
  CrossrefPubMedGoogle Scholar
• 10 Dingfelder JR. Prostaglandin inhibitors: new treatment for an old nemesis. N Engl J Med 1982; 307 (12) 746-747
  CrossrefPubMedGoogle Scholar
• 11 Fishel RS, Barbul A, Beschorner WE, Wasserkrug HL, Efron G. Lymphocyte participation in wound healing. Morphologic assessment using monoclonal antibodies. Ann Surg 1987; 206 (1) 25-29
  CrossrefPubMedGoogle Scholar
• 12 Wahl SM, Hunt DA, Wakefield LM , et al. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A 1987; 84 (16) 5788-5792
  CrossrefPubMedGoogle Scholar
• 13 Grande JP. Role of transforming growth factor-beta in tissue injury and repair. Proc Soc Exp Biol Med 1997; 214 (1) 27-40
  CrossrefPubMedGoogle Scholar
• 14 Greenhalgh DG, Sprugel KH, Murray MJ, Ross R. PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am J Pathol 1990; 136 (6) 1235-1246
  PubMedGoogle Scholar
• 15 Efron JE, Frankel HL, Lazarou SA, Wasserkrug HL, Barbul A. Wound healing and T-lymphocytes. J Surg Res 1990; 48 (5) 460-463
  CrossrefPubMedGoogle Scholar
• 16 Baxter CR. Immunologic reactions in chronic wounds. Am J Surg 1994; 167 (1A) 12S-14S
  CrossrefPubMedGoogle Scholar
• 17 Williamson LM, Sheppard K, Davies JM, Fletcher J. Neutrophils are involved in the increased vascular permeability produced by activated complement in man. Br J Haematol 1986; 64 (2) 375-384
  CrossrefPubMedGoogle Scholar
• 18 Bennett NT, Schultz GS. Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg 1993; 165 (6) 728-737
  CrossrefPubMedGoogle Scholar
• 19 Gallo RL. Proteoglycans and cutaneous vascular defense and repair. J Investig Dermatol Symp Proc 2000; 5 (1) 55-60
  CrossrefPubMedGoogle Scholar
• 20 Iozzo RV. Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem 1998; 67: 609-652
  CrossrefPubMedGoogle Scholar
• 21 Lander AD. Proteoglycans: master regulators of molecular encounter?. Matrix Biol 1998; 17 (7) 465-472
  CrossrefPubMedGoogle Scholar
• 22 Massagué J, Cheifetz S, Boyd FT, Andres JL. TGF-beta receptors and TGF-beta binding proteoglycans: recent progress in identifying their functional properties. Ann N Y Acad Sci 1990; 593: 59-72
  CrossrefPubMedGoogle Scholar
• 23 Kadler K. Extracellular matrix 1: Fibril-forming collagens. Protein Profile 1995; 2 (5) 491-619
  PubMedGoogle Scholar
• 24 Brown JC, Timpl R. The collagen superfamily. Int Arch Allergy Immunol 1995; 107 (4) 484-490
  CrossrefPubMedGoogle Scholar
• 25 Beck K, Brodsky B. Supercoiled protein motifs: the collagen triple-helix and the alpha-helical coiled coil. J Struct Biol 1998; 122 (1–2) 17-29
  CrossrefPubMedGoogle Scholar
• 26 Johnson FR, McMinn RM. The cytology of wound healing of body surfaces in mammals. Biol Rev Camb Philos Soc 1960; 35: 364-412
  CrossrefPubMedGoogle Scholar
• 27 Martin P. Wound healing—aiming for perfect skin regeneration. Science 1997; 276 (5309) 75-81
  CrossrefPubMedGoogle Scholar
• 28 Beer HD, Gassmann MG, Munz B , et al. Expression and function of keratinocyte growth factor and activin in skin morphogenesis and cutaneous wound repair. J Investig Dermatol Symp Proc 2000; 5 (1) 34-39
  CrossrefPubMedGoogle Scholar
• 29 Young PK, Grinnell F. Metalloproteinase activation cascade after burn injury: a longitudinal analysis of the human wound environment. J Invest Dermatol 1994; 103 (5) 660-664
  CrossrefPubMedGoogle Scholar
• 30 Agren MS. Gelatinase activity during wound healing. Br J Dermatol 1994; 131 (5) 634-640
  CrossrefPubMedGoogle Scholar
• 31 Sood R, Achauer BM. Achauer and Sood's Burn Surgery Reconstruction and Rehabilitation. 1st ed. Philadelphia, PA: Elsevier Inc; 2006: 17-26
  Google Scholar
• 32 Battegay EJ, Rupp J, Iruela-Arispe L, Sage EH, Pech M. PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF beta-receptors. J Cell Biol 1994; 125 (4) 917-928
  CrossrefPubMedGoogle Scholar
• 33 Detmar M, Brown LF, Berse B , et al. Hypoxia regulates the expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and its receptors in human skin. J Invest Dermatol 1997; 108 (3) 263-268
  CrossrefPubMedGoogle Scholar
• 34 Bissell MJ, Hall HG, Parry G. How does the extracellular matrix direct gene expression?. J Theor Biol 1982; 99 (1) 31-68
  CrossrefPubMedGoogle Scholar
• 35 Welch MP, Odland GF, Clark RAF. Temporal relationships of F-actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction. J Cell Biol 1990; 110 (1) 133-145
  CrossrefPubMedGoogle Scholar
• 36 Graham MF, Diegelmann RF, Elson CO , et al. Collagen content and types in the intestinal strictures of Crohn's disease. Gastroenterology 1988; 94 (2) 257-265
  PubMedGoogle Scholar
• 37 Graham MF, Blomquist P, Zederfeldt B. The alimentary canal. In: Wound Healing: Biochemical and Clinical Aspects. Philadelphia, PA: WB Saunders; 1992: 433
  Google Scholar
• 38 Graham MF, Drucker DE, Diegelmann RF, Elson CO. Collagen synthesis by human intestinal smooth muscle cells in culture. Gastroenterology 1987; 92 (2) 400-405
  PubMedGoogle Scholar
• 39 Cronin K, Jackson DS, Dunphy JE. Changing bursting strength and collagen content of the healing colon. Surg Gynecol Obstet 1968; 126 (4) 747-753
  PubMedGoogle Scholar
• 40 Hawley PR, Faulk WP, Hunt TK, Dunphy JE. Collagenase activity in the gastro-intestinal tract. Br J Surg 1970; 57 (12) 896-900
  CrossrefPubMedGoogle Scholar
• 41 Irvin TT, Hunt TK. Reappraisal of the healing process of anastomosis of the colon. Surg Gynecol Obstet 1974; 138 (5) 741-746
  PubMedGoogle Scholar
• 42 Jiborn H, Ahonen J, Zederfeldt B. Healing of experimental colonic anastomoses. The effect of suture technic on collagen concentration in the colonic wall. Am J Surg 1978; 135 (3) 333-340
  CrossrefPubMedGoogle Scholar
• 43 Hesp FL, Hendriks T, Lubbers EJ, deBoer HH. Wound healing in the intestinal wall. A comparison between experimental ileal and colonic anastomoses. Dis Colon Rectum 1984; 27 (2) 99-104
  CrossrefPubMedGoogle Scholar
• 44 Stumpf M, Krones CJ, Klinge U, Rosch R, Junge K, Schumpelick V. Collagen in colon disease. Hernia 2006; 10 (6) 498-501
  CrossrefPubMedGoogle Scholar
• 45 Wise L, McAlister W, Stein T, Schuck P. Studies on the healing of anastomoses of small and large intestines. Surg Gynecol Obstet 1975; 141 (2) 190-194
  PubMedGoogle Scholar
• 46 Stumpf M, Klinge U, Wilms A , et al. Changes of the extracellular matrix as a risk factor for anastomotic leakage after large bowel surgery. Surgery 2005; 137 (2) 229-234
  CrossrefPubMedGoogle Scholar
• 47 Baker EA, Leaper DJ. The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology. Eur J Cancer 2003; 39 (7) 981-988
  CrossrefPubMedGoogle Scholar
• 48 Di Colandrea T, Wang L, Wille J, D'Armiento J, Chada KK. Epidermal expression of collagenase delays wound-healing in transgenic mice. J Invest Dermatol 1998; 111 (6) 1029-1033
  CrossrefPubMedGoogle Scholar
• 49 Wang AS, Armstrong EJ, Armstrong AW. Corticosteroids and wound healing: clinical considerations in the perioperative period. Am J Surg 2013; 206 (3) 410-417
  CrossrefPubMedGoogle Scholar
• 50 Beer HD, Longaker MT, Werner S. Reduced expression of PDGF and PDGF receptors during impaired wound healing. J Invest Dermatol 1997; 109 (2) 132-138
  CrossrefPubMedGoogle Scholar
• 51 Hübner G, Brauchle M, Smola H, Madlener M, Fässler R, Werner S. Differential regulation of pro-inflammatory cytokines during wound healing in normal and glucocorticoid-treated mice. Cytokine 1996; 8 (7) 548-556
  CrossrefPubMedGoogle Scholar
• 52 Polat A, Nayci A, Polat G, Aksöyek S. Dexamethasone down-regulates endothelial expression of intercellular adhesion molecule and impairs the healing of bowel anastomoses. Eur J Surg 2002; 168 (8-9) 500-506
  CrossrefPubMedGoogle Scholar
• 53 Durant S, Duval D, Homo-Delarche F. Factors involved in the control of fibroblast proliferation by glucocorticoids: a review. Endocr Rev 1986; 7 (3) 254-269
  CrossrefPubMedGoogle Scholar
• 54 Brauchle M, Fässler R, Werner S. Suppression of keratinocyte growth factor expression by glucocorticoids in vitro and during wound healing. J Invest Dermatol 1995; 105 (4) 579-584
  CrossrefPubMedGoogle Scholar
• 55 Cockayne D, Sterling Jr KM, Shull S, Mintz KP, Illeyne S, Cutroneo KR. Glucocorticoids decrease the synthesis of type I procollagen mRNAs. Biochemistry 1986; 25 (11) 3202-3209
  CrossrefPubMedGoogle Scholar
• 56 Ehrlich HP, Tarver H, Hunt TK. Effects of vitamin A and glucocorticoids upon inflammation and collagen synthesis. Ann Surg 1973; 177 (2) 222-227
  CrossrefPubMedGoogle Scholar
• 57 Gras MP, Verrecchia F, Uitto J, Mauviel A. Downregulation of human type VII collagen (COL7A1) promoter activity by dexamethasone. Identification of a glucocorticoid receptor binding region. Exp Dermatol 2001; 10 (1) 28-34
  CrossrefPubMedGoogle Scholar
• 58 Lindstedt E, Sandblom P. Wound healing in man: tensile strength of healing wounds in some patient groups. Ann Surg 1975; 181 (6) 842-846
  CrossrefPubMedGoogle Scholar
• 59 Sandblom P, Petersen P, Muren A. Determination of the tensile strength of the healing wound as a clinical test. Acta Chir Scand 1953; 105 (1-4) 252-257
  PubMedGoogle Scholar
• 60 Bruewer M, Utech M, Rijcken EJ , et al. Preoperative steroid administration: effect on morbidity among patients undergoing intestinal bowel resection for Crohńs disease. World J Surg 2003; 27 (12) 1306-1310
  CrossrefPubMedGoogle Scholar
• 61 Knudsen L, Christiansen L, Jarnum S. Early complications in patients previously treated with corticosteroids. Scand J Gastroenterol Suppl 1976; 37: 123-128
  PubMedGoogle Scholar
• 62 Post S, Betzler M, von Ditfurth B, Schürmann G, Küppers P, Herfarth C. Risks of intestinal anastomoses in Crohn's disease. Ann Surg 1991; 213 (1) 37-42
  CrossrefPubMedGoogle Scholar
• 63 Ziv Y, Church JM, Fazio VW, King TM, Lavery IC. Effect of systemic steroids on ileal pouch-anal anastomosis in patients with ulcerative colitis. Dis Colon Rectum 1996; 39 (5) 504-508
  CrossrefPubMedGoogle Scholar
• 64 Aberra FN, Lewis JD, Hass D, Rombeau JL, Osborne B, Lichtenstein GR. Corticosteroids and immunomodulators: postoperative infectious complication risk in inflammatory bowel disease patients. Gastroenterology 2003; 125 (2) 320-327
  CrossrefPubMedGoogle Scholar
• 65 Yamamoto T, Allan RN, Keighley MR. Risk factors for intra-abdominal sepsis after surgery in Crohn's disease. Dis Colon Rectum 2000; 43 (8) 1141-1145
  CrossrefPubMedGoogle Scholar
• 66 Sandberg N. Time relationship between administration of cortisone and wound healing in rats. Acta Chir Scand 1964; 127: 446-455
  PubMedGoogle Scholar
• 67 Dostal GH, Gamelli RL. The differential effect of corticosteroids on wound disruption strength in mice. Arch Surg 1990; 125 (5) 636-640
  CrossrefPubMedGoogle Scholar
• 68 Ehrlich HP, Hunt TK. Effects of cortisone and vitamin A on wound healing. Ann Surg 1968; 167 (3) 324-328
  CrossrefPubMedGoogle Scholar
• 69 Alexander AC, Irving MH. Accumulation and pepsin solubility of collagens in the bowel of patients with Crohn's disease. Dis Colon Rectum 1990; 33 (11) 956-962
  CrossrefPubMedGoogle Scholar
• 70 Stumpf M, Cao W, Klinge U , et al. Reduced expression of collagen type I and increased expression of matrix metalloproteinases 1 in patients with Crohn's disease. J Invest Surg 2005; 18 (1) 33-38
  CrossrefPubMedGoogle Scholar
• 71 Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res 2010; 89 (3) 219-229
  CrossrefPubMedGoogle Scholar
• 72 Quattrini C, Jeziorska M, Boulton AJ, Malik RA. Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy. Diabetes Care 2008; 31 (1) 140-145
  CrossrefPubMedGoogle Scholar
• 73 Woo K, Ayello EA, Sibbald RG. The edge effect: current therapeutic options to advance the wound edge. Adv Skin Wound Care 2007; 20 (2) 99-117 , quiz 118–119
  CrossrefPubMedGoogle Scholar
• 74 Gary Sibbald R, Woo KY. The biology of chronic foot ulcers in persons with diabetes. Diabetes Metab Res Rev 2008; 24 (Suppl. 01) S25-S30
  CrossrefPubMedGoogle Scholar
• 75 Flynn MD, Tooke JE. Aetiology of diabetic foot ulceration: a role for the microcirculation?. Diabet Med 1992; 9 (4) 320-329
  CrossrefPubMedGoogle Scholar
• 76 Hennessey PJ, Ford EG, Black CT, Andrassy RJ. Wound collagenase activity correlates directly with collagen glycosylation in diabetic rats. J Pediatr Surg 1990; 25 (1) 75-78
  CrossrefPubMedGoogle Scholar
• 77 Cummings BJ. Effect of preoperative irradiation on the healing of colorectal anastomoses. Am J Surg 1985; 149 (5) 695-697
  CrossrefPubMedGoogle Scholar
• 78 Morgenstern L, Sanders G, Wahlstrom E, Yadegar J, Amodeo P. Effect of preoperative irradiation on healing of low colorectal anastomoses. Am J Surg 1984; 147 (2) 246-249
  CrossrefPubMedGoogle Scholar
• 79 Ormiston MC. A study of rat intestinal wound healing in the presence of radiation injury. Br J Surg 1985; 72 (1) 56-58
  CrossrefPubMedGoogle Scholar
• 80 Thornton FJ, Barbul A. Healing in the gastrointestinal tract. Surg Clin North Am 1997; 77 (3) 549-573
  CrossrefPubMedGoogle Scholar
• 81 Milsom JW, Senagore A, Walshaw RK , et al. Preoperative radiation therapy produces an early and persistent reduction in colorectal anastomotic blood flow. J Surg Res 1992; 53 (5) 464-469
  CrossrefPubMedGoogle Scholar
• 82 Biert J, Wobbes T, Hendriks T, Hoogenhout J. Effect of irradiation on healing of newly made colonic anastomoses in the rat. Int J Radiat Oncol Biol Phys 1993; 27 (5) 1107-1112
  CrossrefPubMedGoogle Scholar
• 83 Weiber S, Jiborn H, Zederfeldt B. Preoperative irradiation and colonic healing. Eur J Surg 1994; 160 (1) 47-51
  PubMedGoogle Scholar
• 84 Adams W, Ctercteko G, Bilous M. Effect of an omental wrap on the healing and vascularity of compromised intestinal anastomoses. Dis Colon Rectum 1992; 35 (8) 731-738
  CrossrefPubMedGoogle Scholar
• 85 Abramowitz HB, Butcher Jr HR. Everting and inverting anastomoses. An experimental study of comparative safety. Am J Surg 1971; 121 (1) 52-56
  CrossrefPubMedGoogle Scholar
• 86 Carter DC, Jenkins DH, Whitfield HN. Omental reinforcement of intestinal anastomoses. An experimental study in the rabbit. Br J Surg 1972; 59 (2) 129-133
  CrossrefPubMedGoogle Scholar
• 87 Cassar K, Munro A. Surgical treatment of incisional hernia. Br J Surg 2002; 89 (5) 534-545
  CrossrefPubMedGoogle Scholar
• 88 Bachman S, Ramshaw B. Prosthetic material in ventral hernia repair: how do I choose?. Surg Clin North Am 2008; 88 (1) 101-112 , ix
  CrossrefPubMedGoogle Scholar
• 89 Breuing K, Butler CE, Ferzoco S , et al; Ventral Hernia Working Group. Incisional ventral hernias: review of the literature and recommendations regarding the grading and technique of repair. Surgery 2010; 148 (3) 544-558
  CrossrefPubMedGoogle Scholar
• 90 Albo D, Awad SS, Berger DH, Bellows CF. Decellularized human cadaveric dermis provides a safe alternative for primary inguinal hernia repair in contaminated surgical fields. Am J Surg 2006; 192 (5) e12-e17
  CrossrefPubMedGoogle Scholar
• 91 Campanelli G, Catena F, Ansaloni L. Prosthetic abdominal wall hernia repair in emergency surgery: from polypropylene to biological meshes. World J Emerg Surg 2008; 3: 33
  CrossrefPubMedGoogle Scholar
• 92 El-Hayek KM, Chand B. Biologic prosthetic materials for hernia repairs. J Long Term Eff Med Implants 2010; 20 (2) 159-169
  CrossrefPubMedGoogle Scholar
• 93 Holton III LH, Kim D, Silverman RP, Rodriguez ED, Singh N, Goldberg NH. Human acellular dermal matrix for repair of abdominal wall defects: review of clinical experience and experimental data. J Long Term Eff Med Implants 2005; 15 (5) 547-558
  CrossrefPubMedGoogle Scholar
• 94 O'Brien JA, Ignotz R, Montilla R, Broderick GB, Christakis A, Dunn RM. Long-term histologic and mechanical results of a Permacol™ abdominal wall explant. Hernia 2011; 15 (2) 211-215
  CrossrefPubMedGoogle Scholar
• 95 Hodde J. Extracellular matrix as a bioactive material for soft tissue reconstruction. ANZ J Surg 2006; 76 (12) 1096-1100
  CrossrefPubMedGoogle Scholar
• 96 Ansaloni L, Catena F, Coccolini F, Negro P, Campanelli G, Miserez M. New “biological” meshes: the need for a register. The EHS Registry for Biological Prostheses: call for participating European surgeons. Hernia 2009; 13 (1) 103-108
  CrossrefPubMedGoogle Scholar
• 97 Candage R, Jones K, Luchette FA, Sinacore JM, Vandevender D, Reed II RL. Use of human acellular dermal matrix for hernia repair: friend or foe?. Surgery 2008; 144 (4) 703-709 , discussion 709–711
  CrossrefPubMedGoogle Scholar
• 98 Gupta A, Zahriya K, Mullens PL, Salmassi S, Keshishian A. Ventral herniorrhaphy: experience with two different biosynthetic mesh materials, Surgisis and Alloderm. Hernia 2006; 10 (5) 419-425
  CrossrefPubMedGoogle Scholar
• 99 Bellows CF, Albo D, Berger DH, Awad SS. Abdominal wall repair using human acellular dermis. Am J Surg 2007; 194 (2) 192-198
  CrossrefPubMedGoogle Scholar
• 100 Blatnik J, Jin J, Rosen M. Abdominal hernia repair with bridging acellular dermal matrix—an expensive hernia sac. Am J Surg 2008; 196 (1) 47-50
  CrossrefPubMedGoogle Scholar
• 101 Jin J, Rosen MJ, Blatnik J , et al. Use of acellular dermal matrix for complicated ventral hernia repair: does technique affect outcomes?. J Am Coll Surg 2007; 205 (5) 654-660
  CrossrefPubMedGoogle Scholar