Lal BK. Venous ulcers of the lower extremity: definition, epidemiology, and economic and social burdens. Semin Vasc Surg. 2015; 28:(1)3-5

Guarnera G, Tinelli G, Abeni D Pain and quality of life in patients with vascular leg ulcers: an Italian multicentre study. J Wound Care. 2007; 16:(8)347-351

Finlayson K, Wu M-L, Edwards HE. Identifying risk factors and protective factors for venous leg ulcer recurrence using a theoretical approach: a longitudinal study. Int J Nurs Stud. 2015; 52:(6)1042-1051

Sen CK, Gordillo GM, Roy S Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009; 17:(6)763-771

Kolluri R. Management of venous ulcers. Tech Vasc Interv Radiol. 2014; 17:(2)132-138

O'Meara S, Al-Kurdi D, Ologun Y Antibiotics and antiseptics for venous leg ulcers. Cochrane Database Syst Rev. 2014; 1

Collins L MD, Seraj S. Diagnosis and treatment of venous ulcers. Am Fam Physician. 2010; 81:(8)989-996

Luz BSR, Araujo CS, Von Atzingen DANC Evaluating the effectiveness of the customized Unna boot when treating patients with venous ulcers. An Bras Dermatol. 2013; 88:(1)41-49

O'Meara S, Cullum N, Nelson EA, Dumville JC. Compression for venous leg ulcers. Cochrane Database Systematic Rev. 2012; 11:(11)

Wong IKY, Andriessen A, Charles HE Randomized controlled trial comparing treatment outcome of two compression bandaging systems and standard care without compression in patients with venous leg ulcers. J Eur Acad Dermatol Venereol. 2012; 26:(1)102-110

Zarchi K, Jemec GBE. Delivery of compression therapy for venous leg ulcers. JAMA Dermatol. 2014; 150:(7)730-736

Chudek J, Mikosiński J, Kobielski A Patients' satisfaction with therapy methods of advanced chronic venous disease. Int Angiol. 2016; 35:(1)98-107

Nair B. Compression therapy for venous leg ulcers. Indian Dermatol Online J. 2014; 5:(3)378-382

Shankaran V, Brooks M, Mostow E. Advanced therapies for chronic wounds: NPWT, engineered skin, growth factors, extracellular matrices. Dermatol Ther. 2013; 26:(3)215-221

Mostow EN, Haraway GD, Dalsing M Effectiveness of an extracellular matrix graft (OASIS Wound Matrix) in the treatment of chronic leg ulcers: a randomized clinical trial. J Vasc Surg. 2005; 41:(5)837-843

Lazarus G, Valle MF, Malas M Chronic venous leg ulcer treatment: future research needs. Wound Repair Regen. 2014; 22:(1)34-42

Jackson N, Waters E. Criteria for the systematic review of health promotion and public health interventions. Health Promot Int. 2005; 20:(4)367-374

Red book: pharmacy's fundamental reference.: Thomson PDR; 2010

Hankin CS, Knispel J, Lopes M Clinical and cost efficacy of advanced wound care matrices for venous ulcers. J Manag Care Pharm. 2012; 18:(5)375-384

Glat P, Orgill DP, Galiano R Placental membrane provides improved healing efficacy and lower cost versus a tissue-engineered human skin in the treatment of diabetic foot ulcerations. Plast Reconstr Surg Glob Open. 2019; 7:(8)

Falanga V, Margolis D, Alvarez O Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Arch Dermatol. 1998; 134:(3)293-300

Vin F, Teot L, Meaume S. The healing properties of Promogran in venous leg ulcers. J Wound Care. 2002; 11:(9)335-341

Kelechi TJ, Mueller M, Hankin CS A randomized, investigatorblinded, controlled pilot study to evaluate the safety and efficacy of a poly-N-acetyl glucosamine-derived membrane material in patients with venous leg ulcers. J Am Acad Dermatol. 2012; 66:(6)e209-e215

Bianchi C, Cazzell S, Vayser D A multicentre randomised controlled trial evaluating the efficacy of dehydrated human amnion/chorion membrane (EpiFix®) allograft for the treatment of venous leg ulcers. Int Wound J. 2018; 15:(1)114-122

Harding K, Sumner M, Cardinal M. A prospective, multicentre, randomised controlled study of human fibroblast-derived dermal substitute (Dermagraft) in patients with venous leg ulcers. Int Wound J. 2013; 10:(2)132-137

Omar AA, Mavor AID, Jones AM, Homer-Vanniasinkam S. Treatment of venous leg ulcers with dermagraft. European J Vasc Endovasc Surg. 2004; 27:(6)666-672

Krishnamoorthy L, Harding K, Griffiths D The clinical and histological effects of Dermagraft in the healing of chronic venous leg ulcers. Phlebology. 2003; 18:(1)12-22

Ehrenreich M, Ruszczak Z. Update on tissue-engineered biological dressings. Tissue Eng. 2006; 12:(9)2407-2424

Organogenesis. Apligraf package insert. 2010. (accessed 20 July 2015)

Tenenhaus M. The use of dehydrated human amnion/chorion membranes in the treatment of burns and complex wounds: current and future applications. Ann Plast Surg. 2017; 78:(2)S11-S13

Organogenesis Inc. Dermagraft: directions for use. 2015. (accessed 20 July 2015)

Shi L, Ronfard V. Biochemical and biomechanical characterization of porcine small intestinal submucosa (SIS): a mini review. Int J Burns Trauma. 2013; 3:(4)173-179

Shi L, Ramsay S, Ermis R, Carson D. In vitro and in vivo studies on matrix metalloproteinases interacting with small intestine submucosa wound matrix. Int Wound J. 2012; 9:(1)44-53

Trengove NJ, Stacey MC, MacAuley S Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors. Wound Repair Regen. 1999; 7:(6)442-452

Vournakis JN, Eldridge J, Demcheva M, Muise-Helmericks RC. Poly-N-acetyl glucosamine nanofibers regulate endothelial cell movement and angiogenesis: dependency on integrin activation of Ets1. J Vasc Res. 2008; 45:(3)222-232

Cullen B, Smith R, McCulloch E Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Repair Regen. 2002; 10:(1)16-25

Phillips TJ, Machado F, Trout R Prognostic indicators in venous ulcers. J Am Acad Dermatol. 2000; 43:(4)627-630

Olin JW, Beusterien KM, Childs MB Medical costs of treating venous stasis ulcers: evidence from a retrospective cohort study. Vasc Med. 1999; 4:(1)1-7

Morrell CJ, Walters SJ, Dixon S Cost effectiveness of community leg ulcer clinics: randomised controlled trial. BMJ. 1998; 316:(7143)1487-1491

Ellison DA, Hayes L, Lane C Evaluating the cost and efficacy of leg ulcer care provided in two large UK health authorities. J Wound Care. 2002; 11:(2)47-51

Clinical and cost efficacy of advanced wound care matrices in the treatment of venous leg ulcers: a systematic review

02 February 2022
19 min read
Volume 6 · Issue 1



Venous leg ulcers (VLUs) are hard-to-heal, recurrent and challenging to treat. Advanced wound care matrices (AWCMs) have been developed to supplement conventional therapies. These costly AWCMs warrant careful comparison as healthcare expenditures are subjected to increasing scrutiny.


This study was designed to compare AWCMs in their ability to heal VLUs and their cost efficacy through a systematic review of randomised controlled trials (RCTs).


An organised search of Medline, Cochrane Library, Central and CINAHL databases identified RCTs that compared AWCMs to standard compression therapy in the healing of VLUs. Bias was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. Eight studies analysing bilayered skin substitute (BSS) (Apligraf), dehydrated human amnion/chorion membrane (dHACM) (Epifix), human fibroblast-derived dermal substitute (HFDDS) (Dermagraft), extracellular wound matrix (ECM) (Oasis), advanced matrix (AM) (Talymed) and matrix wound dressing (MWD) (Promogran) met the inclusion criteria.


Four studies reported significant improvement over standard therapy: BSS, dHACM, ECM and AM. Incremental cost per additional successful treatment was determined for each trial, ranging from $2593 (MWD) to $210,800 (HFDDS).


Our consolidated analysis of eight major RCTs of AWCMs in the treatment of VLUs revealed a great variation in clinical and cost efficacy among these products. The included trials were inconsistent in methodology, and these limitations should be noted, but, in the absence of RCTs to compare these products, our systematic review may serve as a guide for practitioners who seek to optimise wound healing while considering cost efficacy.

Venous leg ulcers (VLUs) are a prevalent condition, affecting as much as 1% of the population, and up to 4% of individuals over 65 years of age.1 They have a deleterious impact on lifestyle,2 are hard-to-heal and recurrent in nature, and are challenging to treat successfully.3

The treatment of VLUs accounts for a significant portion of healthcare expenditure in the US, with cost exceeding an estimated $2.5–3.5 billion annually.4 This cost is driven by provider care, compression therapy regimens, antibiotic therapy, procedures such as venous ablation and attempted wound closures, and dressings such as advanced wound care matrices (AWCMs). This does not include the economic impact of lost work days and productivity. High recurrence rates frustrate both the provider and patient and further stress cost of care to the healthcare system.

Conventional therapy for VLUs is multifaceted in nature. Wound cleansing and debridement should be performed at the initial evaluation and as needed at each subsequent dressing change in order to provide the proper environment for healing. In addition to products used for cleansing, topical dressings, such as alginates and foams, are supportive for maintenance of this optimal healing environment.5,6

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