Early healing events in a porcine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis, and healing

A porcine model of wound healing was employed to examine the impact of nanocrystalline silver–coated dressings on specific wound healing events. Full‐thickness wounds were created on the backs of pigs, contaminated with an experimental inoculum containing Pseudomonas aeruginosa, Fusobacterium sp., and coagulase‐negative staphylococci, and covered with dressing products either containing silver or not. Nanocrystalline silver‐coated dressings promoted rapid wound healing, particularly during the first several days post‐injury. Healing was characterized by rapid development of well vascularized granulation tissue that supported tissue grafting 4 days post‐injury, unlike control dressed wounds. The proteolytic environment of wounds treated with nanocrystalline silver was characterized by reduced levels of matrix metalloproteinases. Matrix metalloproteinases have been shown to be present in chronic ulcers at abnormally high levels, as compared with acute wounds, and may contribute to the nonhealing nature of these wounds. Cellular apoptosis occurred at a higher frequency in the nanocrystalline silver–treated wounds than in wounds dressed with other products. The results suggest that nanocrystalline silver may play a role in altering or compressing the inflammatory events in wounds and facilitating the early phases of wound healing. These benefits are associated with reduced local matrix metalloproteinase levels and enhanced cellular apoptosis. (WOUND REP REG 2002;10:)

[1]  S. Zinkgraf,et al.  Lower respiratory tract abnormalities in rheumatoid interstitial lung disease. Potential role of neutrophils in lung injury. , 1987, The American review of respiratory disease.

[2]  H. S. Bennett,et al.  Science and art in preparing tissues embedded in plastic for light microscopy, with special reference to glycol methacrylate, glass knives and simple stains. , 1976, Stain technology.

[3]  J. Wallace Lipid mediators of inflammation in gastric ulcer. , 1990, The American journal of physiology.

[4]  G. Schultz,et al.  Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[5]  P. D’Amore,et al.  Growth Factors and Angiogenesis in Wound Healing , 1997 .

[6]  H. Ceri,et al.  Anti-inflammatory benefits of tilmicosin in calves with Pasteurella haemolytica-infected lungs. , 1998, American journal of veterinary research.

[7]  V. Kähäri,et al.  Matrix metalloproteinases in skin , 1997, Experimental dermatology.

[8]  D L Evans,et al.  Analysis and discrimination of necrosis and apoptosis (programmed cell death) by multiparameter flow cytometry. , 1992, Biochimica et biophysica acta.

[9]  N. Hogg,et al.  Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis , 1990, Nature.

[10]  A. Buret,et al.  Tilmicosin Induces Apoptosis in Bovine Peripheral Neutrophils in the Presence or in the Absence of Pasteurella haemolytica and Promotes Neutrophil Phagocytosis by Macrophages , 2000, Antimicrobial Agents and Chemotherapy.

[11]  S. Pollack The wound healing process. , 1984, Clinics in dermatology.

[12]  S. Miller,et al.  Bacteriology of chronic leg ulcers. , 1978, Archives of dermatology.

[13]  D. Keast,et al.  Preparing the wound bed--debridement, bacterial balance, and moisture balance. , 2000, Ostomy/wound management.

[14]  I. K. Cohen,et al.  Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids. , 1996, The Journal of investigative dermatology.

[15]  J. Cohen,et al.  Apoptosis in leukocytes , 1995, Journal of leukocyte biology.

[16]  M. Robson Wound Infection: A Failure of Wound Healing Caused by an Imbalance of Bacteria , 1997 .

[17]  J I Gallin,et al.  Current concepts: immunology. Neutrophils in human diseases. , 1987, The New England journal of medicine.

[18]  R. Diegelmann,et al.  Ability of chronic wound fluids to degrade peptide growth factors is associated with increased levels of elastase activity and diminished levels of proteinase inhibitors , 1997, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[19]  J. Zimmerman,et al.  Neutrophil mediators, Pseudomonas, and pulmonary dysfunction in cystic fibrosis. , 1993, The Journal of laboratory and clinical medicine.

[20]  P. Birrer Proteases and antiproteases in cystic fibrosis: pathogenetic considerations and therapeutic strategies. , 1995, Respiration; international review of thoracic diseases.

[21]  J. Kaplan,et al.  Chemical modification as an approach to elucidation of sodium pump structure-function relations. , 1990, The American journal of physiology.

[22]  A. Desmoulière,et al.  Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury. , 1997, The international journal of biochemistry & cell biology.

[23]  Jon R. Cohen The Molecular and Cellular Biology of Wound Repair , 1997, Springer US.

[24]  I. K. Cohen,et al.  Physiology of the chronic wound. , 1998, Clinics in plastic surgery.

[25]  Usa Serono Symposia,et al.  Growth factors and wound healing : basic science and potential clinical applications , 1997 .

[26]  P. Henson,et al.  Tissue injury in inflammation. Oxidants, proteinases, and cationic proteins. , 1987, The Journal of clinical investigation.

[27]  A. Harken,et al.  Mechanisms of neutrophil-mediated tissue injury. , 1991, The Journal of surgical research.

[28]  H. Westh,et al.  Bacterial colonization and healing of venous leg ulcers , 1996, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[29]  A. Desmoulière,et al.  Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. , 1995, The American journal of pathology.

[30]  C. Owen,et al.  Leukocyte proteinases in wound healing: roles in physiologic and pathologic processes , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[31]  D. Yager,et al.  The proteolytic environment of chronic wounds , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[32]  W. H. Mager,et al.  Glycosaminoglycans in human skin , 1973, The British journal of dermatology.

[33]  A. Rogers,et al.  Involvement of proteolytic enzymes—plasminogen activators and matrix metalloproteinases—in the pathophysiology of pressure ulcers , 1995, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[34]  L. Sandholm Proteases and their inhibitors in chronic inflammatory periodontal disease. , 1986, Journal of clinical periodontology.

[35]  H. Ehrlich The physiology of wound healing. A summary of normal and abnormal wound healing processes. , 1998, Advances in wound care : the journal for prevention and healing.

[36]  A. Vaheri,et al.  Proteolytic activity in leg ulcer exudate , 1993, Experimental dermatology.

[37]  J. Savill Apoptosis in resolution of inflammation , 1997, Journal of leukocyte biology.

[38]  B. Hirschel,et al.  GRANULATION TISSUE AS A CONTRACTILE ORGAN: A STUDY OF STRUCTURE AND FUNCTION , 1972 .

[39]  R. Burrell,et al.  Wound management in an era of increasing bacterial antibiotic resistance: a role for topical silver treatment. , 1998, American journal of infection control.

[40]  Richard A.F. Clark,et al.  The Molecular and Cellular Biology of Wound Repair , 2012, Springer US.