Research Article| Volume 65, ISSUE 1, P91-99, January 2012

Histological evolution of chronic wounds under negative pressure therapy

Published:September 01, 2011DOI:



      Negative pressure wound therapy (NPT) has achieved widespread success in the treatment of difficult wounds. However, its effects are but partially explored, and investigations mostly concentrated at the wound–dressing interface; a detailed histological description of the evolution of wounds under NPT is still lacking.

      Materials and Methods

      Subsequent punch biopsies of NPT-treated chronic wounds of human patients were analysed. Phenomena occurring in wounds were quantified by analysis of proliferating cells nuclear antigen (PCNA) (proliferating nuclei), CD31 (blood vessels), CD68p (macrophages) and CD45 (lymphocytes) stained slides.


      Three layers were identified in day-0 wounds. Over time, under NPT, the layers behaved differently: the most superficial (1.5 mm) developed granulation tissue, constant in thickness, with high proliferation index, increased in blood vessels density and developed acute inflammation. Instead, the two deeper layers decreased in proliferation rate, maintained vessels density unchanged, were cleared of chronic inflammation and oedema and underwent progression towards stable tissue.


      Indeed, while most research has focused on induction of superficial granulation tissue by NPT, deeper layers appear to be also affected, with relieving of chronic inflammation and tissue stabilisation. This may be an important and under-appreciated effect, playing a role in the known positive outcomes of NPT, such as better graft-taking rates.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Plastic, Reconstructive & Aesthetic Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Morykwas M.J.
        • Simpson J.
        • Punger K.
        • et al.
        Vacuum-assisted closure: state of basic research and physiologic foundation.
        Plast Reconstr Surg. 2006; 117: 121S-126S
        • Orgill D.P.
        • Manders E.K.
        • Sumpio B.E.
        • et al.
        The mechanisms of action of vacuum assisted closure: More to learn.
        Surgery. 2009; 146: 40-51
        • Torbrand C.
        • Ugander M.
        • Engblom H.
        • et al.
        Wound contraction and macro-deformation during negative pressure therapy of sternotomy wounds.
        J Cardiothorac Surg. 2010; 5: 75
        • Moues C.M.
        • Vos M.C.
        • van den Bemd G.J.
        • et al.
        Bacterial load in relation to vacuum-assisted closure wound therapy: A prospective randomized trial.
        Wound Repair Regen. 2004; 12: 11-17
        • Weed T.
        • Ratliff C.
        • Drake D.B.
        Quantifying bacterial bioburden during negative pressure wound therapy: does the wound VAC enhance bacterial clearance?.
        Ann Plast Surg. 2004; 52 (discussion 279–80): 276-279
        • Braakenburg A.
        • Obdeijn M.C.
        • Feitz R.
        • et al.
        The clinical efficacy and cost effectiveness of the vacuum-assisted closure technique in the management of acute and chronic wounds: a randomized controlled trial.
        Plast Reconstr Surg. 2006; 118 (discussion 398–400): 390-397
        • Scherer S.S.
        • Pietramaggiori G.
        • Mathews J.C.
        • et al.
        Short periodic applications of the vacuum-assisted closure device cause an extended tissue response in the diabetic mouse model.
        Plast Reconstr Surg. 2009; 124: 1458-1465
        • Malmsjo M.
        • Lindstedt S.
        • Ingemansson R.
        Influence on pressure transduction when using different drainage techniques and wound fillers (foam and gauze) for negative pressure wound therapy.
        Int Wound J. 2010; 7: 406-412
        • Morykwas M.J.
        • Argenta L.C.
        • Shelton-Brown E.I.
        • et al.
        Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation.
        Ann Plast Surg. 1997; 38: 553-562
        • Labler L.
        • Rancan M.
        • Mica L.
        • et al.
        Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds.
        J Trauma. 2009; 66: 749-757
        • Saxena V.
        • Hwang C.W.
        • Huang S.
        • et al.
        Vacuum-assisted closure: microdeformations of wounds and cell proliferation.
        Plast Reconstr Surg. 2004; 114 (discussion 1097–8): 1086-1096
        • Huang S.
        • Ingber D.E.
        Shape-dependent control of cell growth, differentiation, and apoptosis: switching between attractors in cell regulatory networks.
        Exp Cell Res. 2000; 261: 91-103
        • Pietramaggiori G.
        • Liu P.
        • Scherer S.S.
        • et al.
        Tensile forces stimulate vascular remodeling and epidermal cell proliferation in living skin.
        Ann Surg. 2007; 246: 896-902
        • Scherer S.S.
        • Pietramaggiori G.
        • Mathews J.C.
        • et al.
        The mechanism of action of the vacuum-assisted closure device.
        Plast Reconstr Surg. 2008; 122: 786-797
        • Chin M.S.
        • Ogawa R.
        • Lancerotto L.
        • et al.
        In vivo acceleration of skin growth using a servo-controlled stretching device.
        Tissue Eng Part C. Methods. 2010; 16: 397-405
        • Chin M.S.
        • Lancerotto L.
        • Helm D.L.
        • et al.
        Analysis of neuropeptides in stretched skin.
        Plast Reconstr Surg. 2009; 124: 102-113
        • Chen S.Z.
        • Li J.
        • Li X.Y.
        • et al.
        Effects of vacuum-assisted closure on wound microcirculation: an experimental study.
        Asian J Surg. 2005; 28: 211-217
        • Murphey G.C.
        • Macias B.R.
        • Hargens A.R.
        Depth of penetration of negative pressure wound therapy into underlying tissues.
        Wound Repair Regen. 2009; 17: 113-117
        • Wilkes R.
        • Zhao Y.
        • Cunningham K.
        • et al.
        3D strain measurement in soft tissue: demonstration of a novel inverse finite element model algorithm on MicroCT images of a tissue phantom exposed to negative pressure wound therapy.
        J Mech Behav Biomed Mater. 2009; 2: 272-287
        • Kairinos N.
        • Solomons M.
        • Hudson D.A.
        The paradox of negative pressure wound therapy–in vitro studies.
        J Plast Reconstr Aesthet Surg. 2010; 63: 174-179
        • Kairinos N.
        • Solomons M.
        • Hudson D.A.
        Negative-pressure wound therapy I: the paradox of negative-pressure wound therapy.
        Plast Reconstr Surg. 2009; 123 (discussion 599–600): 589-598
        • Kairinos N.
        • Voogd A.M.
        • Botha P.H.
        • et al.
        Negative-pressure wound therapy II: negative-pressure wound therapy and increased perfusion. just an illusion?.
        Plast Reconstr Surg. 2009; 123: 601-612
        • Labanaris A.P.
        • Polykandriotis E.
        • Horch R.E.
        The effect of vacuum-assisted closure on lymph vessels in chronic wounds.
        J Plast Reconstr Aesthet Surg. 2009; 62: 1068-1075
        • Jacobs S.
        • Simhaee D.A.
        • Marsano A.
        • et al.
        Efficacy and mechanisms of vacuum-assisted closure (VAC) therapy in promoting wound healing: a rodent model.
        J Plast Reconstr Aesthet Surg. 2009; 62: 1331-1338
        • Singer A.J.
        • Clark R.A.
        Cutaneous wound healing.
        N Engl J Med. 1999; 341: 738-746
        • Broughton 2nd, G.
        • Janis J.E.
        • Attinger C.E.
        Wound healing: an overview.
        Plast Reconstr Surg. 2006; 117: 1e-S-32e-S
        • Korber A.
        • Franckson T.
        • Grabbe S.
        • et al.
        Vacuum assisted closure device improves the take of mesh grafts in chronic leg ulcer patients.
        Dermatology. 2008; 216: 250-256