Science, Practice and Education

1Malin MalmsjöMD, PhDProfessor and Senior Consultant

2Sandra Lindstedt MD, PhD

2Richard Ingemansson MD, PhD

1Lotta Gustafsson MD, PhD

1Department of Ophthalmology

2Department of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, Sweden

Correspondence:malin.malmsjo@med.lu.se

Conflict of interest: This review was supported by Abigo Medical AB

AbStRActIn recent years, intensive research has been conducted to investigate the bio-logical effects of negative-pressure wound therapy (NPWT) on the wound bed and to find ways to optimize the use of this technology. The mechanisms by which NPWT may lead to accelerated wound healing include the creation of a moist environment, drainage of exudate, reduc-tion of tissue oedema, contraction of the wound edges, mechanical stimulation of the wound bed, blood flow changes in the wound edges, stimulation of angiogenesis and formation of granulation tissue. The choice of wound filler partly determines the effects of NPWT on the wound bed. Foam and gauze are the most frequently used wound fillers for NPWT. Bacteria and fungus binding mesh (Sorbact®) constitutes an interesting new alternative wound filler. In light of the lack of a ran-domized, controlled trial, this review pro-vides some insight on some of the latest preclinical findings regarding the choice of wound filler to optimize NPWT for the individual wound.

IntRoductIonNegative pressure wound therapy (NPWT) is increas-ingly used to treat hard-to-heal wounds and has been shown to improve healing outcomes in many wound types, including orthopedic trauma1, soft tissue trau-ma2, skin grafts3, flaps, pressure ulcers4, venous leg ulcers5, vascular surgery wounds, diabetic foot ulcers6, burns7, wound dehiscence, in abdominal8 and thoracic surgery9 and surgical infections10.

Initially, the wound is filled with a wound filler (commonly foam or gauze) to allow pressure to be transmitted and evenly distributed to the bottom of the wound. The wound is then sealed with an adhesive drape and a drain is connected to a vacuum pump that applies the negative pressure. Wound fluid is withdrawn by the negative pressure and collected in a canister.

NPWT accelerates wound healing by initiating a cascade of interrelated biological reactions that ulti-mately lead to wound healing. NPWT has been found to create a moist wound healing environment11, drain exudate12-14, reduce tissue edema15, contract wound edges12-14, mechanically stimulate the wound bed16-18, alter blood flow in the wound edges13, 19-22 and stimu-late angiogenesis23, 24 and the formation of granulation tissue13. The biological effects of NPWT are repre-sented in Figure 1.

thE nEGAtIvE PRESSuRE LEvELThe most commonly used negative pressure level is -125 mm Hg13. However, more recent studies have shown that the maximum biological effects on the wound edges, in terms of wound contraction,25 regional blood flow26 and the formation of granulation tissue27, are obtained at -80 mmHg. A recent case report28 show that negative pressure levels lower than -125 mm Hg indeed result in excellent wound healing. When us-ing NPWT to treat poorly perfused tissue (e.g., dia-betic foot ulcers and thin skin transplants), ischemia may develop in the wound tissue and the patient can

Bacteria and fungus binding mesh in negative pressure wound therapy A review of the biological effects in the wound bed

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thE wound fILLERFoam and gauze are the most frequently used wound fill-ers in NPWT (Figure 2 and 3). Nearly all foam used for NPWT is made of polyurethane and has an open cell structure with a pore size of 400 - 600 µm. The gauze is a type of cotton gauze (AMD gauze)30. It is believed that the wound filler may determine the effects on wound heal-ing. Bacteria and fungus binding mesh (Sorbact®) may constitute an interesting alternative (Figure 2 and 3). The pathogen binding mesh is a woven acetate material that is coated with dialkyl carbomoyl chloride (DACC). Such mesh makes use of the hydrophobic interaction to re-move pathogens.31. Bacteria and fungus binding mesh is known to adsorb and inactivates a wide range of bacteria, e.g. Staphylococcus aureus and Pseudomonas aeruginosa, as well as fungi, and has been shown to reduce the micro-bial load without the development of resistance among microorganisms.

The biological effects on the wound edge by NPWT, using bacteria and fungus binding mesh as compared to conventional wound fillers (foam and gauze), is being re-viewed and summarized in this article.

Figure 1. Application of NPWT: First, the wound is debrided. The wound then is filled with a material that will deliver nega-tive pressure to the wound bed – in this case, foam. The wound is sealed with an adhesive plastic drape and a drain is connected to the vacuum pump.

The pressure applied by the vacuum pump is propagated through the wound filler to the wound bed, leading to the removal of exudate. Some of the biological effects of the therapy are illustrated in the image. Blood flow close to the wound edge (white) de-creases; whereas, hyperperfusion is seen further away (red). The wound is contracted and fluid is evacuated through the drainage tube.

References

1. Bollero D, Carnino R, Risso D, Gangemi EN, Stella M. Acute complex traumas of the lower limbs: a modern reconstructive approach with negative pressure therapy. Wound Repair Regen 2007; 15(4):589-94.

2. Stannard JP, Robinson JT, Anderson ER, McGwin G, Jr., Volgas DA, Alonso JE. Negative pressure wound therapy to treat hematomas and surgical incisions following high-energy trauma. J Trauma 2006; 60(6):1301-6.

3. Scherer LA, Shiver S, Chang M, Meredith JW, Owings JT. The vacuum assisted closure device: a method of securing skin grafts and improving graft survival. Arch Surg 2002; 137(8):930-3; discussion 933-4.

4. Joseph E, Hamori C, Bergman S, Roaf E, Swann N. A new prospective randomized trial of Vacuum assisted closure versus standard therapy of chronic nonhealing wounds. Wounds 2000; 12:60-7.

5. Vuerstaek JD, Vainas T, Wuite J, Nelemans P, Neumann MH, Veraart JC. State-of-the-art treatment of chronic leg ulcers: A randomized controlled trial comparing vacuum-assisted closure (V.A.C.) with modern wound dressings. J Vasc Surg 2006; 44(5):1029-37; discussion 1038.

6. Armstrong DG, Lavery LA. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet 2005; 366(9498):1704-10.

7. Kamolz LP, Andel H, Haslik W, Winter W, Meissl G, Frey M. Use of subatmospheric pressure therapy to prevent burn wound progression in human: first experiences. Burns 2004; 30(3):253-8.

8. Wild T, Stortecky S, Stremitzer S, Lechner P, Humpel G, Glaser K, Fortelny R, Karner J, Sautner T.Abdominal dressing -- a new standard in therapy of the open abdomen following secondary peritonitis?]. Zentralbl Chir 2006; 131 Suppl 1:S111-4.

9. Sjogren J, Gustafsson R, Nilsson J, Malmsjo M, Ingemansson R. Clinical outcome after poststernotomy mediastinitis: vacuum-assisted closure versus conventional treatment. Ann Thorac Surg 2005; 79(6):2049-55.

10. Ozturk E, Ozguc H, Yilmazlar T. The use of vacuum assisted closure therapy in the management of Fournier’s gangrene. Am J Surg 2009; 197(5):660-5; discussion 665.

11. Banwell PE. Topical negative pressure therapy in wound care. J Wound Care 1999; 8(2):79-84.

12. Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg 1997; 38(6):563-76; discussion 577.

13. Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W. Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic founda-tion. Ann Plast Surg 1997; 38(6):553-62.

PRESSuRE tRAnSductIon And wound fLuId dRAInAGEThe function of the wound filler is to transmit the nega-tive pressure from the vacuum pump and tubing to the wound bed. It has been shown that the negative pressure is equally well transmitted through bacteria and fungus binding mesh (Sorbact®), foam and gauze16, 32 .

The negative pressure affects only the tissue in direct contact with the wound filler and does not extend to deeper structures. It is therefore important to place the wound filler in all areas of the wound where the effect of the negative pressure is desired33. When draining fluid from a deep wound pocket the entire pocket needs to be filled with the dressing. In these circumstances, it may be easier to use pathogen binding mesh or gauze, than foam, because of the moldability and ease of application to irregular wounds32, 34. Another advantage with using bacteria and fungus binding mesh or gauze is that granula-tion tissue does not grow into these materials and there is less risk of the wound filler getting stuck in the wound27.

experience pain during treatment29. Thus, it may be advantageous to use a lower level of negative pressure in the treatment of sensitive, poorly perfused tissue. Negative 40 mmHg is the pressure level at which about half the maximum blood flow effect is achieved26, and may be a suitable negative pressure level to try in these types of wounds. The use of negative pressures higher than -80 mmHg does not provide any additional effects on wound edge microvascular blood flow26. Drainage may be improved at -125 mmHg25, and this level of negative pressure could be used for the first few days to treat high-output wounds, after which the negative pressure may be lowered once the amount of exudate lessens.

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Science, Practice and Education

The suction force generated by the negative pres-sure leads to active drainage of exudate from the wound. Wound fluid is known to be efficiently removed by foam and pathogen binding mesh while more fluid is retained in gauze32. The reason for this may be that both foam and the pathogen binding mesh are hydrophobic allowing the fluid to pass through the material. The wound fluid removal is advantageous as it reduces cytokines and other compounds that are inhibitory to wound healing, such as proteolytic enzymes and metalloproteinases35, 36.

NPWT instillation technique is now beginning to be used more frequently. By automatically delivering topi-cal solutions to the wound site, the NPWT instillation technique combines the proven benefits of NPWT with the advantages of instillation therapy37-39.

MEchAnIcAL EffEctSOne of the fundamental effects of NPWT is believed to be the deformation of the wound edge tissue as the wound contracts (macrodeformation)23, 30, 40. It has been shown that the wound contraction is similar for pathogen bind-

ing mesh (Sorbact®) and gauze, while slightly greater for foam32, as a result of its slightly more open and spongy texture.

The wound bed and wound filler also interact on a microscopic level (microdeformation). The wound bed is drawn into the pores of the foam or in-between the threads of the gauze and pathogen binding mesh18. His-tological examination of cross sections of the wound bed after NPWT using bacteria and fungus binding mesh, foam and gauze has shown that these materials all result in microdeformation of the wound bed41.

These mechanical effects are thought to result in shearing forces at the wound–dressing interface, which affect the cytoskeleton18, and initiate a signalling cascade that ultimately leads to granulation tissue formation and wound healing. The pulling together of the wound edg-es by negative pressure may be important for the entire wound-healing process, as early reduction in the size of the wound has been shown to be correlated with improved final wound healing42.

Figure 2: Photos of bacteria and fungus binding mesh (Sorbact®), foam and gauze before the dressing is applied to the wound.

Figure 3: Representative photos of the wound during treatment with a negative pressure wound therapy using bacteria and fungus binding mesh (Sorbact®), foam and gauze.

14. Morykwas MJ, Simpson J, Punger K, Argenta A, Kremers L, Argenta J. Vacuum-assisted closure: state of basic research and physiologic foundation. Plast Reconstr Surg 2006; 117(7 Suppl):121S-126S.

15. Lu X, Chen S, Li X, al. e. The experimental study of the effects of vacuum-assisted closure on edema and vessel permeability of the wound. Chinese Journal of Clinical Rehabilitation 2003; 7:1244-5.

16. Malmsjo M, Ingemansson R, Martin R, Huddleston E. Negative-pressure wound therapy using gauze or open-cell polyurethane foam: similar early effects on pressure transduction and tissue contraction in an experimental porcine wound model. Wound Repair Regen 2009; 17(2):200-5.

17. Borgquist O, Gustafsson L, Ingemansson R, Malmsjo M. Micro- and macromechani-cal effects on the wound bed of negative pressure wound therapy using gauze and foam. Ann Plast Surg 2010; 64(6):789-93.

18. Saxena V, Hwang CW, Huang S, Eichbaum Q, Ingber D, Orgill DP. Vacuum-assist-ed closure: microdeformations of wounds and cell proliferation. Plast Reconstr Surg 2004; 114(5):1086-96; discussion 1097-8.

19. Kairinos N, Voogd AM, Botha PH, Kotze T, Kahn D, Hudson DA, Solomons M. Negative-pressure wound therapy II: negative-pressure wound therapy and increased perfusion. Just an illusion? Plast Reconstr Surg 2009; 123(2):601-12.

20. Wackenfors A, Gustafsson R, Sjogren J, Algotsson L, Ingemansson R, Malmsjo M. Blood flow responses in the peristernal thoracic wall during vacuum-assisted closure therapy. Ann Thorac Surg 2005; 79(5):1724-30; discussion 1730-1.

21. Wackenfors A, Sjogren J, Gustafsson R, Algotsson L, Ingemansson R, Malmsjo M. Effects of vacuum-assisted closure therapy on inguinal wound edge microvascular blood flow. Wound Repair Regen 2004; 12(6):600-6.

22. Timmers MS, Le Cessie S, Banwell P, Jukema GN. The effects of varying degrees of pressure delivered by negative-pressure wound therapy on skin perfusion. Ann Plast Surg 2005; 55(6):665-71.

23. Chen SZ, Li J, Li XY, Xu LS. Effects of vacuum-assisted closure on wound microcir-culation: an experimental study. Asian J Surg 2005; 28(3):211-7.

24. Greene AK, Puder M, Roy R, Arsenault D, Kwei S, Moses MA, Orgill DP. Microdefor-mational wound therapy: effects on angiogenesis and matrix metalloproteinases in chronic wounds of 3 debilitated patients. Ann Plast Surg 2006; 56(4):418-22.

25. Borgquist O, Ingemansson R, Malmsjo M. The influence of low and high pressure levels during negative-pressure wound therapy on wound contraction and fluid evacuation. Plast Reconstr Surg 2011; 127(2):551-9.

26. Borgquist O, Ingemansson R, Malmsjo M. Wound edge microvascular blood flow during negative-pressure wound therapy: examining the effects of pressures from -10 to -175 mmHg. Plast Reconstr Surg 2010; 125(2):502-9.

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bLood fLow EffEctS The effects on blood flow resulting from NPWT are local and vary depending on the distance from the wound edge (see Figure 1)20. Blood flow decreases close to the edge of the wound (within about 5 mm) and increases farther away from the wound edge (about 25 mm)20, 21, 26. The increase in blood flow has been shown to be similar for bacteria and fungus binding mesh (Sorbact®), and foam and gauze, while the decrease in blood flow is more pronounced with foam than with the other materials32.

This combination of increased and decreased blood flow is believed to be advantageous in the wound healing process. Increased blood flow may lead to improved oxy-gen and nutrient supply to the tissue, as well as improved penetration of antibiotics and removal of waste products. Blood flow reduction in the superficial tissue occurs in response to the negative pressure compressing the tissue surface43, 44. The mechanism behind the increase in blood flow has not yet been identified, but it has been speculated that the negative pressure causes a force in the tissue that opens up the vascular bed, increasing flow.

There are both advantages and disadvantages of the hypoperfusion caused by NPWT. It is well-known that reduced blood flow stimulates angiogenesis and granula-tion tissue formation, which in turn facilitate the process of wound healing12, 45. However, several clinical problems are associated with hypoperfusion. In tissues with already impaired circulation, the further decrease in blood flow may result in ischemia, and it has been suggested that NPWT should be applied with caution to tissues with compromised vascularity19. Some advocate that NPWT is contraindicated if there is any doubt about the vascularity of the tissue46, 47. The way in which NPWT is adminis-tered should therefore be based on the type of wound and its vascularity.

Two different strategies can be used to tailor NPWT to alter the degree of hypoperfusion generated in the wound edge: changing the negative pressure level, or the type of

wound filler. Pathogen binding mesh and gauze caused less pronounced hypoperfusion than foam, which may be the result of the smaller degree of wound contraction than with foam. The use of foam may be beneficial in maximizing hypoperfusion thus stimulating angiogenesis, while bacteria and fungus binding mesh or gauze may be preferable when the vascularization of the tissue is in doubt, and there is a risk of ischaemia.

GRAnuLAtIon tISSuE foRMAtIonGranulation tissue is the combination of small vessels and connective tissue that forms in the wound bed. It provides a matrix that allows epidermal cells to migrate over the bed of the wound. NPWT is known to accelerate the formation of granulation tissue compared to conventional therapy13. The amount and character of the granulation tissue differ depending on the type of wound filler17, 27,

41, 48. The granulation tissue formed under foam is thick but fragile, while that under gauze is thinner but denser17, 27, 48. The granulation tissue formed under bacteria and fungus binding mesh has properties between that of foam and gauze41.

The wound filler for NPWT may thus be chosen to suit particular wounds49. Thick granulation tissue is beneficial for fast wound healing, but may lead to problems such as fibrosis, scarring and contractures as the wound heals48. Foam is thus suitable for wounds that benefit from thick granulation tissue and where scarring does not pose a prob-lem, for example, in sternotomy wounds50, or fasciotomy wounds in upper or lower limb compartment syndrome where contraction is beneficial51, and in acute wounds with large tissue loss providing a bridging therapy1, 2. Gauze has become especially popular among plastic sur-geons for wound-bed preparation before grafting52, and is the filler of choice when the cosmetic result is more important than the speed of wound healing, or in cases where scar tissue may restrict movement, for example,

27. Borgquist O, Gustafsson L, Ingemansson R, Malmsjo M. Tissue Ingrowth Into Foam but Not Into Gauze During Negative Pressure Wound Therapy. Wounds 2009; 21(11):302-9.

28. Nease C. Using low pressure, negative pressure wound therapy for wound prepara-tion and the management of split-thickness skin grafts in three patients with complex wounds. Ostomy Wound Manage 2009; 55(6):32-42.

29. Hurd T, Chadwick P, Cote J, Cockwill J, Mole TR, Smith JM. Impact of gauze-based NPWT on the patient and nursing experience in the treatment of challenging wounds. Int Wound J 2010.

30. Campbell PE, Smith GS, Smith JM. Retrospective clinical evaluation of gauze-based negative pressure wound therapy. Int Wound J 2008; 5(2):280-6.

31. Borgquist O, Ingemansson R, Lindstedt S, Malmsjo M.In Process Citation]. Lakartidningen 2011; 108(46):2372-5.

32. Malmsjo M, Ingemansson R, Lindstedt S, Gustafsson L. Comparison of bacteria and fungus-binding mesh, foam and gauze as fillers in negative pressure wound therapy - pressure transduction, wound edge contraction, microvascular blood flow and fluid retention. Int Wound J 2012.

33. Torbrand C, Ingemansson R, Gustafsson L, Paulsson P, Malmsjo M. Pressure transduction to the thoracic cavity during topical negative pressure therapy of a sternotomy wound. Int Wound J 2008; 5(4):579-84.

34. Jeffery LC. Advanced wound therapies in the management of severe military lower limb trauma: a new perspective. Eplasty 2009; 9:e28.

35. Yager DR, Nwomeh BC. The proteolytic environment of chronic wounds. Wound Repair Regen 1999; 7(6):433-41.

36. Armstrong DG, Jude EB. The role of matrix metalloproteinases in wound healing. J Am Podiatr Med Assoc 2002; 92(1):12-8.

37. Fleischmann W, Russ M, Westhauser A, Stampehl M.Vacuum sealing as carrier system for controlled local drug administration in wound infection]. Unfallchirurg 1998; 101(8):649-54.

38. Lehner B, Fleischmann W, Becker R, Jukema GN. First experiences with negative pressure wound therapy and instillation in the treatment of infected orthopaedic implants: a clinical observational study. Int Orthop 2011; 35(9):1415-20.

39. Timmers MS, Graafland N, Bernards AT, Nelissen RG, van Dissel JT, Jukema GN. Negative pressure wound treatment with polyvinyl alcohol foam and polyhexanide antiseptic solution instillation in posttraumatic osteomyelitis. Wound Repair Regen 2009; 17(2):278-86.

40. Etöz A ÖY, Özcan M. The use of negative pressure wound therapy on diabetic foot ulcers: a preliminary controlled trial. Wounds 2004(16):264-9.

41. Malmsjo M, Lindstedt S, Ingemansson R, Gustafsson L. Use of bacteria and fungus binding mesh in negative pressure wound therapy provides significant granulation tissue without tissue ingrowth. Eplasty In press.

42. Lavery LA, Barnes SA, Keith MS, Seaman JW, Jr., Armstrong DG. Prediction of healing for postoperative diabetic foot wounds based on early wound area progres-sion. Diabetes Care 2008; 31(1):26-9.

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Figure 4: Representative hematoxylin-eosin stained sections of biopsies from wound beds after 72 hours of NPWT using bacteria and fungus binding mesh (Sorbact®), foam or gauze. The ingrowth of tissue into the foam is indicated by arrows. No such ingrowth can be seen in the pathogen binding mesh or gauze.

over joints. Bacteria and fungus binding mesh (Sorbact®) produces a granulation tissue with characteristics between those formed with foam and gauze, providing clinicians with another wound filler option in their efforts to obtain optimal healing effects.

InGRowthA number of complications are associated with tissue ingrowth into foam. Firstly, the patient may experience pain during dressing changes as the ingrown tissue is torn away from the wound53, requiring the administration of strong analgesics54, 55. Secondly, wound-bed disruption and mechanical tissue damage may arise as the foam is removed from the wound bed during dressing changes. Thirdly, pieces of foam may become stuck in the wound bed and, if not removed, will act as foreign bodies that may impede wound healing. It is therefore common that a non-adherent wound contact layer is placed between the

wound bed and the wound filler, when the clinician an-ticipates such complications56, 57. It is now known that the degree of ingrowth differs depending on the type of wound filler used for NPWT. Wound bed tissue grows into the foam, but not into pathogen binding mesh (Sorbact®) or gauze (Figure 4)41. This is probably due to differences in the physical properties of the dressings and the interac-tion between tissue and dressing at a microscopic level14.

IndIvIduAL oPtIMIzAtIon of tREAtMEnt Today, the negative pressure level, the wound filler mate-rial (foam or gauze) and the mode (continuous, intermit-tent, or variable) by which the pressure is applied can be tailored to the individual wound. Results of in vivo re-search carried out during the past few years on the mecha-nisms involved have shown how the healing process can be influenced by varying these parameters. Much of this research has been carried out on pigs, but interestingly, experienced clinicians have come to the same conclusions when it comes to treating patients. Knowledge of how to tailor the differ parameters of the NPWT to the individual wound is now beginning to be employed in patient care to minimize complications (such as ischemia and pain) and to optimize outcome.

concLuSIonSBacteria and fungus binding mesh (Sorbact®) is an inter-esting alternative wound filler in NPWT. It produces a significant amount of granulation tissue in the wound bed, more than with gauze, without the problems of ingrowth, as is the case with foam. Furthermore, bacteria and fungus binding mesh has the advantage of being easy to apply, like gauze, to irregular and deep pocket wounds. Efficient wound fluid removal in combination with its pathogen binding properties makes hydrophobic mesh an interesting alternative wound filler in NPWT. m

43. Kairinos N, Solomons M, Hudson DA. The paradox of negative pressure wound therapy--in vitro studies. J Plast Reconstr Aesthet Surg; 63(1):174-9.

44. Kairinos N, Solomons M, Hudson DA. Negative-pressure wound therapy I: the paradox of negative-pressure wound therapy. Plast Reconstr Surg 2009; 123(2):589-98; discussion 599-600.

45. Petzina R, Gustafsson L, Mokhtari A, Ingemansson R, Malmsjo M. Effect of vacuum-assisted closure on blood flow in the peristernal thoracic wall after internal mammary artery harvesting. Eur J Cardiothorac Surg 2006; 30(1):85-9.

46. Venturi ML, Attinger CE, Mesbahi AN, Hess CL, Graw KS. Mechanisms and clinical applications of the vacuum-assisted closure (VAC) Device: a review. Am J Clin Dermatol 2005; 6(3):185-94.

47. Attinger CE, Janis JE, Steinberg J, Schwartz J, Al-Attar A, Couch K. Clinical approach to wounds: debridement and wound bed preparation including the use of dressings and wound-healing adjuvants. Plast Reconstr Surg 2006; 117(7 Suppl):72S-109S.

48. Fraccalvieri M. Negative Pressure Wound Therapy (NPWT) using gauze and foam: histological, immuno-histochemical and ultrasonography morphological analysis of the granulation tissue and scar tissue. Preliminary report of a clinical study. Int Wound J May 2011; Aug(8(4)):355-64.

49. Malmsjö M, Borgquist O. NPWT settings and dressing choices made easy. Wounds International 2010; 1(3).

50. Gustafsson RI, Sjogren J, Ingemansson R. Deep sternal wound infection: a sternal-sparing technique with vacuum-assisted closure therapy. Ann Thorac Surg 2003; 76(6):2048-53; discussion 2053.

51. Zannis J, Angobaldo J, Marks M, DeFranzo A, David L, Molnar J, Argenta L. Comparison of fasciotomy wound closures using traditional dressing changes and the vacuum-assisted closure device. Ann Plast Surg 2009; 62(4):407-9.

52. Chariker ME, Gerstle TL, Morrison CS. An algorithmic approach to the use of gauze-based negative-pressure wound therapy as a bridge to closure in pediatric extremity trauma. Plast Reconstr Surg 2009; 123(5):1510-20.

53. Malmsjo M, Gustafsson L, Lindstedt S, Ingemansson R. Negative pressure wound therapy-associated tissue trauma and pain: a controlled in vivo study comparing foam and gauze dressing removal by immunohistochemistry for substance P and calcitonin gene-related peptide in the wound edge. Ostomy Wound Manage 2011; 57(12):30-5.

54. Franczyk M, Lohman RF, Agarwal JP, Rupani G, Drum M, Gottlieb LJ. The impact of topical lidocaine on pain level assessment during and after vacuum-assisted closure dressing changes: a double-blind, prospective, randomized study. Plast Reconstr Surg 2009; 124(3):854-61.

55. Krasner DL. Managing wound pain in patients with vacuum-assisted closure devices. Ostomy Wound Manage 2002; 48(5):38-43.

56. Blakely M, Weir D. The innovative use of Safetac soft silicone in conjunction with negative pressure wound therapy: three case studies. poster at SAWC 2007.

57. Dunbar A, Bowers DM, Holderness H, Jr. Silicone net dressing as an adjunct with negative pressure wound therapy. Ostomy Wound Manage 2005; 51(11A Sup-pl):21-2.

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