Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2013 Jan 31;2013(1):CD001737.
doi: 10.1002/14651858.CD001737.pub4.

Skin grafting for venous leg ulcers

June E Jones  1 , E Andrea Nelson, Aws Al-Hity
Affiliations
Meta-Analysis

Skin grafting for venous leg ulcers

June E Jones et al. Cochrane Database Syst Rev. .

Abstract

Background: Venous leg ulceration is a recurrent, chronic, disabling condition. It affects up to one in 100 people at some time in their lives. Standard treatments are simple dressings and compression bandages or stockings. Sometimes, despite treatment, ulcers remain open for months or years. Sometimes skin grafts are used to stimulate healing. These may be taken, or grown into a dressing, from the patient's own uninjured skin (autografts), or applied as a sheet of bioengineered skin grown from donor cells (allograft). Preserved skin from other animals, such as pigs, has also been used (xenografts).

Objectives: To assess the effect of skin grafts for treating venous leg ulcers.

Search methods: For this update we modified the search strategies and conducted searches of The Cochrane Wounds Group Specialised Register (searched 27 July 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7); Ovid MEDLINE (2008 to July Week 3 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, July 26, 2012); Ovid EMBASE (2008 to 2012 Week 29); and EBSCO CINAHL (2008 to 26 July 2012). We did not apply date or language restrictions.

Selection criteria: Randomised controlled trials (RCTs) of skin grafts in the treatment of venous leg ulcers.

Data collection and analysis: Two review authors independently undertook data extraction and assessment of study quality.

Main results: For this update of the review, we identified one new trial, bringing the total to 17 trials (1034 participants) - all of which were generally at moderate or high risk of bias. In 12 trials participants also received compression bandaging.Eleven trials compared a graft with standard care in which no graft was used. Two of these trials (102 participants) compared a dressing with an autograft; three trials (80 participants) compared frozen allografts with dressings, and two trials (45 participants) compared fresh allografts with dressings. Two trials (345 participants) compared tissue-engineered skin (bilayer artificial skin) with a dressing. In two trials (97 participants) a single-layer dermal replacement was compared with standard care.Six trials compared alternative skin grafting techniques. The first trial (92 participants) compared autografts with frozen allograft, a second (51 participants) compared a pinch graft (autograft) with porcine dermis (xenograft), the third (110 participants) compared growth-arrested human keratinocytes and fibroblasts with placebo, the fourth (10 participants) compared an autograft delivered on porcine pads with an autograft delivered on porcine gelatin microbeads, the fifth trial (92 participants) compared a meshed graft with a cultured keratinocyte autograft, and the sixth trial (50 participants) compared a frozen keratinocyte allograft with a lyophilised (freeze-dried) keratinocyte allografts.Significantly more ulcers healed when treated with bilayer artificial skin than with dressings. There was insufficient evidence from the other trials to determine whether other types of skin grafting increased the healing of venous ulcers.

Authors' conclusions: Bilayer artificial skin, used in conjunction with compression bandaging, increases venous ulcer healing compared with a simple dressing plus compression. Further research is needed to assess whether other forms of skin grafts increase ulcer healing.

PubMed Disclaimer

Conflict of interest statement

Andrea Nelson was co‐applicant and trial co‐ordinator for one of the trials included in this review (Iglesias 2004); this trial was commissioned after the first version of this review was completed. Andrea Nelson was trial co‐ordinator and author of the main publication for one of the trials included in this review (Nelson 2007a).

June Jones and Aws Al‐Hity ‐ none.

Figures

1
1
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Split‐thickness autografts compared with standard care, Outcome 1 Healing.
2.1
2.1. Analysis
Comparison 2 Frozen or fresh allografts compared with standard care, Outcome 1 Healing.
3.1
3.1. Analysis
Comparison 3 Bilayered human skin equivalent compared with standard care, Outcome 1 Healing.
4.1
4.1. Analysis
Comparison 4 Single‐layered dermal skin replacement compared with standard care, Outcome 1 Healing.
5.1
5.1. Analysis
Comparison 5 Allogenic tissue product compared with placebo, Outcome 1 Complete wound closure.
6.1
6.1. Analysis
Comparison 6 Autograft versus comparator graft, Outcome 1 Proportion fully healed in trial.
6.2
6.2. Analysis
Comparison 6 Autograft versus comparator graft, Outcome 2 Reduction in ulcer area.
7.1
7.1. Analysis
Comparison 7 Autograft on microbeads compared with autograft on pads, Outcome 1 Healing.
8.1
8.1. Analysis
Comparison 8 Autograft versus cultured autologous keratinocytes, Outcome 1 Number of ulcers healed at 12 weeks.
9.1
9.1. Analysis
Comparison 9 Frozen allograft compared with lyophilised keratinocyte, Outcome 1 Healing.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Brown‐Etris 2000 {published data only}
    1. Brown‐Etris M, Shields DK, Galluzzi KE, Steinberg JS, Shalen AB, Barnes HR, et al. Preliminary clinical outcomes on the use of composite cultured skin for the healing of venous ulcers. 13th Annual Symposium on Advanced Wound Care and 10th Annual Medical Research Forum on Wound Repair; 2000, 1‐4 April; Dallas, Texas. 2000:D5.
Burdge 2000 {published data only}
    1. Burdge J, Cope F, Abbruzzese B, Wille J. Long‐term healing of venous stasis ulcers treated with serum‐free cultured epidermal autografts. Eleventh Annual Meeting and Educational Symposuim Wound Healing Society; 2001, 16‐18 May; Albuquerque, New Mexico. 2001:146.
    1. Burdge J, Swanson N, Pittelkow M, Cope F, Abbruzzese B, Schaefer S, et al. Successful treatment of venous stasis leg ulcers with a cultured autologous epidermal graft. Wound Healing Society Educational Symposium; 2000, 4‐6 June; Toronto, Canada. 2000:10.
Duhra 1992 {published data only}
    1. Duhra P, Blight A, Mountford E, Cheshire I, Withers A, Ilchyshyn A. A randomized controlled trial of cultured keratinocyte allografts for chronic venous ulcers. Journal of Dermatological Treatment 1992;3:189‐91.
Falanga 1998 {published data only}
    1. Atillasoy E. The safety and efficacy of Graftskin (APLIGRAF) in the treatment of venous leg ulcers: a multicenter, randomized, controlled clinical trial. Wounds ‐ A Compendium of Clinical Research and Practice 2000;12(Suppl A):20A‐6A.
    1. Falanga V, Margolis D, Alvarez O, Auletta M, Maggiacomo F, Altman M, et al. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Archives of Dermatology 1998;134:293‐300. - PubMed
    1. Falanga V, Sabolinski M. A bilayered living skin construct (APLIGRAF) accelerates complete closure of hard‐to‐heal venous ulcers. Wound Repair and Regeneration 1999;7:201‐7. - PubMed
    1. Sabolinski M, Rovee D, Parenteau N, Mulder G, Jensen J. The efficacy and safety of graftskin for the treatment of chronic venous ulcers. 5th Annual Meeting of the Wound Healing Society and the Regeneration Forum; 1994, 27‐30 April; Minneapolis USA. 1995:78.
    1. Sabolinski ML, Alvarez O, Auletta M, Mulder G, Parenteau NL. Cultured skin as a 'smart material' for healing wounds: experience in venous ulcers. Biomaterials 1996;17:311‐20. - PubMed
Goedkoop 2010 {published data only}
    1. Goedkoop R, Juliet R, You PHK, Daroczy J, Roos K, Lijnen R, et al. Wound stimulation by growth‐arrested human keratinocytes and fibroblasts: HP802‐247, a new‐generation allogenic tissue engineering product. Dermatology 2010;220:114‐20. - PubMed
Jankunas 2007 {published data only}
    1. Jankunas V, Bagdonas R, Samsanavicius D, Rimdeika R. An analysis of the effectiveness of skin grafting to treat chronic venous leg ulcers. Wounds: A Compendium of Clinical Research and Practice 2007;19(5):128‐37. - PubMed
Krishnamoorthy 2003 {published data only}
    1. Harding KG, Brassard A, Dolynchuck K, Leaper D, Poskitt K, Sibbald RG. A pilot study to determine the effect of human dermal replacement in treating hard‐to‐heal venous leg ulcers. Proceedings of the 13th Annual Symposium on Advanced Wound Care & 10th Annual Medical Research Forum on Wound Repair. USA: HMP Communications, LLC. 2000:C68.
    1. Krishnamoorthy L, Harding KG, Griffiths D, Moore K, Leaper D, Poskitt K, et al. The clinical and histological effects of Dermagraft® in the healing of chronic venous leg ulcers. Phlebology 2003;18(1):12‐22.
Lindgren 1998 {published data only}
    1. Lindgren C, Marcusson J, Toftgard R. Treatment of venous leg ulcers with cryopreserved cultured allogeneic keratinocytes: a prospective open controlled study. British Journal of Dermatology 1998;139:271‐5. - PubMed
Liu 2004 {published data only}
    1. Liu JY, Hafner J, Dragieva G, Seifert B, Burg G. Autologous cultured keratinocytes on porcine gelatin microbeads effectively heal chronic venous leg ulcers. Wound Repair and Regeneration 2004;12(2):148‐56. - PubMed
Navratilova 2004 {published data only}
    1. Navratilova Z. Cryopreserved and lyophilized cultured epidermal allografts in the treatment of leg ulcers. 20th World Congress of Dermatology. 2002. - PubMed
    1. Navratilova Z, Slonkova V, Semradova V, Adler J. Cryopreserved and lyophilized cultured epidermal allografts in the treatment of leg ulcers: a pilot study. Journal of the European Academy of Dermatology & Venereology 2004;18(2):173‐9. - PubMed
Omar 2004 {published data only}
    1. Omar AA, Mavor AI, Jones AM, Homer‐Vanniasinkam S. Treatment of venous leg ulcers with Dermagraft. European Journal of Vascular and Endovascular Surgery 2004;27(6):666‐72. - PubMed
Paquet 2005 {published data only}
    1. Paquet P, Quatresooz P, Braham C, Piérard GE. Tapping into the influence of keratinocyte allografts and biocenosis on healing of chronic leg ulcers: split‐ulcer controlled pilot study. Dermatologic Surgery 2005;31(4):431‐5. - PubMed
Poskitt 1987 {published data only}
    1. Poskitt K, James A, Lloyd‐Davies E, Walton J, McCollum C. Pinch skin grafting or porcine dermis in venous ulcers: a randomised clinical trial. British Medical Journal 1987;294:674‐6. - PMC - PubMed
Salomon 2002 {published data only}
    1. Salomon D. Epidex: a new treatment for recalcitrant chronic leg ulcers (abstract). 20th World Congress of Dermatology; 2002, 1‐5 July; Paris. 2002.
Tausche 2003 {published data only}
    1. Tausche A, Skaria M, Bohlen L, Liebold K, Hafner J, Friedlein H, et al. An autologous epidermal equivalent tissue‐engineered from follicular outer root sheath keratinocytes is as effective as split‐thickness skin autograft in recalcitrant vascular leg ulcers. Wound Repair and Regeneration 2003;11(4):248‐52. - PubMed
Teepe 1993 {published data only}
    1. Teepe R, Roseeuw D, Hermans J, Koebrugge E, Altena T, Coninck A, et al. Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers. Journal of the American Academy of Dermatology 1993;29(6):982‐8. - PubMed
Warburg 1994 {published data only}
    1. Warburg F, Danielsen L, Madsen S, Raaschou H, Munkvad S, Jensen R, et al. Vein surgery with or without skin grafting versus conservative treatment for leg ulcers. Acta Dermatologica Venereologica (Stockholm) 1994;74(4):307‐9. - PubMed

References to studies excluded from this review

Ahnlide 1997 {published data only}
    1. Ahnlide I, Bjellerup M. Efficacy of pinch grafting in leg ulcers of different aetiologies. Acta Dermatologica Venereologica (Stockholm) 1997;77:144‐5. - PubMed
Altman 1997 {published data only}
    1. Altman MI. Treatment of venous ulcers with human skin equivalent [letter]. Journal of the American Podiatric Medical Association 1997;87(8):392‐4. - PubMed
Andersen 1959 {published data only}
    1. Andersen MN, Stephens JG. A controlled study of surgical treatment and pathogenesis of stasis ulcers. Annals of Surgery 1959;150:57‐62. - PMC - PubMed
Beele 1991 {published data only}
    1. Beele H, Naeyaert JM, Goeteyn M, Mil M, Kint A. Repeated cultured epidermal allografts in the treatment of chronic leg ulcers of various origins. Dermatologica 1991;183(1):31‐5. - PubMed
Berretty 1979 {published data only}
    1. Berretty PJ, Neumann HA, Limpens AM, Cormane RH. Treatment of ulcers on legs from venous hypertension by split‐thickness skin grafts. Journal of Dermatology, Surgery and Oncology 1979;5(12):966‐70. - PubMed
Boyce 1995 {published data only}
    1. Boyce ST, Glatter R, Kitzmiller WJ. Case studies: treatment of chronic wounds with cultured skin substitutes. Ostomy/Wound Management 1995;41(2):26‐8, 30, 32 passim. - PubMed
Calonge 1993 {published data only}
    1. Calonge H, Ruszczak Z, Stadler R. Human cultured epidermal auto‐ and allografts for wound healing. New method for in vitro epidermis reconstruction. Proceedings of the 1st Joint Meeting of the Wound Healing Society and the European Tissue Repair Society. 22‐25 August 1993. Amsterdam, The Netherlands:85.
Carpentier 2009 {published data only}
    1. Carpentier P. Venous ulcer: the final stage in chronic venous disease ‐ managing it in 2009 (Pierre Fabre Symposium). Phlebolymphology 2010;17(1):28‐9.
Carver 1991 {published data only}
    1. Carver N, Leigh IM. Keratinocyte grafts and skin equivalents. International Journal of Dermatology 1991;30(8):540‐51. - PubMed
Chang 2000 {published data only}
    1. Chang DW, Sancheez LA, Veith FJ, Wain RA, Okhi T, Suggs WD. Can a tissue‐engineered skin graft improve healing of lower extremity foot wounds after revascularization?. Annals of Vascular Surgery 2000;14(1):44‐9. - PubMed
Christiansen 1997 {published data only}
    1. Christiansen J, Ek L, Tegner E. Pinch grafting of leg ulcers. A retrospective study of 412 treated ulcers in 146 patients. Acta Dermatologica Venereologica 1997;77(6):471‐3. - PubMed
Clancy 1988 {published data only}
    1. Clancy JM, Shehade SA, Blight AE, Young KE, Levick PL. Treatment of leg ulcers with cultured epithelial grafts. Journal of the American Academy of Dermatology 1988;18(6):1356‐7. - PubMed
Coney 1990 {published data only}
    1. Coney M, Donatien PH, Beylot C, Geniaux M, Maleville J, Bezian JH, et al. Treatment of leg ulcers with an allogenic cultured‐keratinocyte‐collagen dressing. Clinical and Experimental Dermatology 1990;15:410‐4. - PubMed
Dahlstrom 1992 {published data only}
    1. Dahlstrom KK, Weis Fogh US, Medgyesi S, Rostgaard J, Sorensen H. The use of autologous fibrin adhesive in skin transplantation. Plastic and Reconstructive Surgery 1992;89(5):968‐72. - PubMed
Demling 2004 {published data only}
    1. Demling RH, Niezgoda JA, Haraway GD, Mostow EN. Small intestinal submucosa wound matrix and full‐thickness venous ulcers: preliminary results. Wounds: A Compendium of Clinical Research and Practice 2004;16(1):18‐22.
Fahey 1998 {published data only}
    1. Fahey C. Experience with a new human skin equivalent for healing venous leg ulcers. Journal of Vascular Nursing 1998;16(1):11‐5. - PubMed
Farah 2010 {published data only}
    1. Farah R, Davis MDP. Venous leg ulceration: a treatment update. Current Treatment Options in Cardiovascular Medicine 2010;12(2):101‐16. - PubMed
Halter 2003 {published data only}
    1. Halter G, Kapfer X, Liewald F, Bischoff M. Vacuum‐sealed mesh graft transplantation in chronic cutaneous ulcers of the lower leg. VASA 2003;32:155‐8. - PubMed
Harris 1993 {published data only}
    1. Harris IR, Bottomley W, Wood EJ, Cunliffe WJ. Use of autografts for the treatment of leg ulcers in elderly patients. Clinical Experimental Dermatology 1993;18(5):417‐20. - PubMed
Harrison 1988 {published data only}
    1. Harrison PV. Split‐skin grafting of varicose leg ulcers ‐ a survey and the importance of assessment of risk factors in predicting outcome from the procedure. Clinical Experimental Dermatology 1988;13(1):4‐6. - PubMed
Henderson 1980 {published data only}
    1. Henderson HP, Marples RR, Richardson JF. Comparison of topical antibacterial agents in the preparation of varicose ulcers for skin grafting. Journal of Hospital Infection 1980;1(2):141‐7. - PubMed
Kirsner 1997 {published data only}
    1. Kirsner RS, Eaglstein WH, Kerdel FA. Split‐thickness skin grafting for lower extremity ulcerations. Dermatologic Surgery 1997;23:85‐91. - PubMed
Leigh 1986 {published data only}
    1. Leigh IM, Purkis PE. Culture grafted leg ulcers. Clinical Experimental Dermatology 1986;11(6):650‐2. - PubMed
Limova 1995 {published data only}
    1. Limova M, Mauro T. Treatment of leg ulcers with cultured epithelial autografts: clinical study and case reports. Ostomy/Wound Management 1995;41(8):48‐50, 52, 54‐60. - PubMed
Mahajan 1995 {published data only}
    1. Mahajan R, Mosley JG. Use of a semipermeable polyamide dressing over skin grafts to venous leg ulcers. British Journal of Surgery 1995;82(10):1359‐60. - PubMed
Marcusson 1992 {published data only}
    1. Marcusson JA, Lindgren C, Berghard A, Toftgard R. Allogeneic cultured keratinocytes in the treatment of leg ulcers: a pilot study. Acta Dermatologica Venereologica 1992;72(1):61‐4. - PubMed
Mekkes 1992 {published data only}
    1. Mekkes JR, Westerhof W. Excising necrotic venous ulcers, by using absorbing polysaccharide pads [Debridement van necrotische veneuze ulcera met behulp van absorberende polysaccharide pads]. Therapie, Geneesmiddel en Onderzoek 1992;17(9):253‐7.
Millard 1977 {published data only}
    1. Millard LG, Roberts MM, Gatecliffe M. Chronic leg ulcers treated by the pinch graft method. British Journal of Dermatology 1977;97(3):289‐95. - PubMed
Mol 1991 {published data only}
    1. Mol M, Nanninga B, Eendenburg J, Westerhof W, Mekkes J, Ginkel C. Grafting of venous leg ulcers. Journal of the American Academy of Dermatology 1991;24(1):77‐82. - PubMed
Mostow 2005 {published data only}
    1. Mostow E, Haraway G, Dalsing M, Hodde J, King D. Effectiveness of an extracellular matrix graft (OASIS Wound Matrix) in the treatment of chronic leg ulcers: a randomized clinical trial. Journal of Vascular Surgery 2005;41(5):837‐43. - PubMed
Muhart 1998 {published data only}
    1. Muhart M, McFalls S, Kirsner R, Kerdel F, Eaglstein WH. Bioengineered skin. Lancet 1998;350:1142. - PubMed
O'Donnell 2006 {published data only}
    1. O'Donnell Jr TF, Lau J. A systematic review of randomized controlled trials of wound dressings for chronic venous ulcers. Journal of Vascular Surgery 2006;44(5):1118‐25. - PubMed
Oien 1998 {published data only}
    1. Oien R, Hansen B, Hakansson A. Pinch grafting of leg ulcers in primary care. Acta Dermatologica Venereologica (Stockholm) 1998;78:438‐9. - PubMed
Ortega 2010 {published data only}
    1. Ortega Z, Hunziker T, Lauchi S, Mayer DO, Huber C, Baumann C, et al. Epidex Swiss field trial. 2004‐2008. Dermatology 2010;221(4):365‐72. - PubMed
Phillips 1991a {published data only}
    1. Phillips TJ, Kehinde O, Green H, Gilchrest BA. Treatment of skin ulcers with cultured epidermal allografts. Journal of the American Academy of Dermatology 1989;21(2 Pt 1):191‐9. - PubMed
Phillips 1991b {published data only}
    1. Phillips TJ. Cultured epidermal allografts ‐ a temporary or permanent solution?. Transplantation 1991;51(5):937‐41. - PubMed
Pojda 1994 {published data only}
    1. Pojda Z, Struzyna J. New method for treatment of the non‐healing wounds with the split thickness skin grafts preincubated with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). 4th Annual Meeting of the European Tissue Repair Society; 1994, 25‐28 August; Oxford, England. 1994:201.
Puonti 1998 {published data only}
    1. Puonti H, Asko Seljavaara S. Excision and skin grafting of leg ulcers. Annales Chirurgiae Gynaecologiae 1998;87(3):219‐23. - PubMed
Ruffieux 1997 {published data only}
    1. Ruffieux P, Hommel L, Saurat JH. Long‐term assessment of chronic leg ulcer treatment by autologous skin grafts. Dermatology 1997;195(1):77‐80. - PubMed
Shehade 1989 {published data only}
    1. Shehade S, Clancy J, Blight A, Young K, Levick P. Cultured epithelial allografting of leg ulcers. Journal of Dermatological Treatment 1989;1/2:79‐81.
Skene 1992 {published data only}
    1. Skene AI, Smith JM, Dore CJ, Charlett A, Lewis JD. Venous leg ulcers: a prognostic index to predict time to healing. BMJ 1992;305(6862):1119‐21. - PMC - PubMed
Slonkova 2002 {published data only}
    1. Slonkova V, Navratilova Z, Semradova V, Adler J. Cultures epidermal keratinocytes in the treatment of leg ulcers. Part 11. Comparison of the effect of cryopreserved and lyophilized allografts. Cesko‐Slovenska Dermatologie 2002;77(6):239‐44.
Steele 1985 {published data only}
    1. Steele K. Pinch grafting for chronic venous leg ulcers in general practice. Journal of the Royal College of General Practitioners 1985;35(281):574‐5. - PMC - PubMed
Townsend 1970 {published data only}
    1. Townsend J. Skin grafting leg ulcers. Lancet 1970;1(7636):39. - PubMed
Trent 1998 {published data only}
    1. Trent JF, Kirsner RS. Tissue engineered skin: Apligraf, a bi‐layered living skin equivalent. International Journal of Clinical Practice 1998;52(6):408‐13. - PubMed
Van den Hoogenband 1984 {published data only}
    1. Hoogenband HM. Treatment of leg ulcers with split‐thickness skin grafts. Journal of Dermatology, Surgery and Oncology 1984;10(8):605‐8. - PubMed
Villeneuve 1998 {published data only}
    1. Villeneuve P, Hafner J, Prenosil JE, Elsner P, Burg G. A novel culturing and grafting system for the treatment of leg ulcers. British Journal of Dermatology 1998;138(5):849‐51. - PubMed
Vin 2002 {published data only}
    1. Vin F, Teot L, Meaume S. The healing properties of Promogran in venous leg ulcers. Journal of Wound Care 2002;11(9):335‐41. - PubMed
Ward 1989 {published data only}
    1. Ward DJ, Bennett JP, Burgos H, Fabre J. The healing of chronic venous leg ulcers with prepared human amnion. British Journal of Plastic Surgery 1989;42(4):463‐7. - PubMed

References to studies awaiting assessment

Wille 2011 {published data only}
    1. Wille JJ, Burdge JJ, Pitttelkow MR. Rapid healing of chronic venous stasis leg ulcers treated by the application of a novel serum‐free cultured autologous epidermis. Wound Repair and Regeneration 2011;19(4):464‐74. - PubMed

Additional references

Apligraf 2010
    1. Organogenesis. Apligraf: add life after healing. http://www.apligraf.com/. Organogenesis Inc., 2010.
Baker 1992
    1. Baker SR, Stacey MC, Singh G, Hoskin SE, Thompson PJ. Aetiology of chronic leg ulcers. European Journal of Vascular Surgery 1992;6:245‐51. - PubMed
Barrandon 1987
    1. Barrandon Y, Green G. Three clonal type keratinocytes with different capacities for multiplication. Proceedings of the National Academy of Science (USA) 1987;84:2302‐6. - PMC - PubMed
Barwell 2004
    1. Barwell JR, Davies CE, Deacon J, Harvey K, Minor J, Sassano A, et al. Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial. Lancet 2004;363:1854‐9. - PubMed
Bosanquet 1992
    1. Bosanquet N. Costs of venous ulcers ‐ from maintenance therapy to investment programs. Phlebology 1992;7:44‐6.
Callam 1985
    1. Callam MJ, Ruckley CV, Harper DR, Dale JJ. Chronic ulceration of the leg: extent of the problem and the provision of care. British Medical Journal 1985;290(6485):1855‐6. - PMC - PubMed
Callam 1989
    1. Callam MJ. Chronic leg ulceration: the Lothian and Forth Valley Leg Ulcer Study. University of Dundee: ChM Thesis, 1989.
Charles 1995
    1. Charles H. The impact of leg ulcers on patients' quality of life. Professional Nurse 1995;10:571‐4. - PubMed
Compton 1995
    1. Compton CC, Tong Y, Trookman N, Zhao H, Roy D, Press W. Transforming growth factor and gene expression in cultured human keratinocytes is unaffected by cellular ageing. Archives of Dermatology 1995;131:683‐90. - PubMed
Enoch 2005
    1. Enoch S, Shaaban H, Dunn KW. Informed consent should be obtained from patients to use products (skin substitutes) and dressings containing biological material. Journal of Medical Ethics 2005;31:2‐6. - PMC - PubMed
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Altman DG, on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group (Editors). Chapter 8. Assessing risk of bias in included studies. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Lees 1992
    1. Lees TA, Lambert D. Prevalence of lower limb ulceration in an urban health district. British Journal of Surgery 1992;79:1032‐4. - PubMed
Lefebvre 2011
    1. Lefebvre C, Manheimer E, Glanville J, on behalf of the Cochrane Information Retrieval Methods Group. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Margolis 2004
    1. Margolis DJ, Allen‐Taylor L, Hoffstad O, Berlin JA. The accuracy of venous leg ulcer prognostic models in a wound care system. Wound Repair and Regeneration 2004;12(2):163‐8. - PubMed
Phillips 1989
    1. Phillips T, Kehinde O, Green H, Gilchrest BA. Treatment of skin ulcers with cultured epidermal allografts. Journal of the American Academy of Dermatology 1989;21(2 Pt 1):191‐9. - PubMed
SIGN 2011
    1. Scottish Intercollegiate Guidelines Network (SIGN). Search filters. http://www.sign.ac.uk/methodology/filters.html#random 2011.

Publication types