Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a systematic review

The outcome of management of diabetic foot ulcers remains a challenge, and there remains continuing uncertainty concerning optimal approaches to management. It is for these reasons that in 2008 and 2012, the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing published systematic reviews of the evidence to inform protocols for routine care and to highlight areas, which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between June 2010 and June 2014. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound and other systemic therapies, which did not fit in the aforementioned categories. Heterogeneity of studies prevented pooled analysis of results. Of the 2161 papers identified, 30 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic reviews, and the conclusion is similar: that with the possible exception of negative pressure wound therapy in post‐operative wounds, there is little published evidence to justify the use of newer therapies. Analysis of the evidence continues to present difficulties in this field as controlled studies remain few and the majority continue to be of poor methodological quality.

[1]  J. Dumville,et al.  Negative pressure wound therapy for treating foot wounds in people with diabetes mellitus. , 2018, The Cochrane database of systematic reviews.

[2]  Irfan Shukr,et al.  Comparison of Negative Pressure Wound Therapy Using Vacuum-Assisted Closure with Advanced Moist Wound Therapy in the Treatment of Diabetic Foot Ulcers. , 2015, Journal of the College of Physicians and Surgeons--Pakistan : JCPSP.

[3]  M. Löndahl,et al.  Comments on Margolis et al. Lack of effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation , 2015, International wound journal.

[4]  Malik Irfan Ahmed,et al.  A comparison of efficacy of topical use of phenytoin and vaseline gauze dressing with vaseline gauze dressing alone in healing of diabetic foot ulcers , 2014 .

[5]  D. Cucinotta,et al.  The effect of PDRN, an adenosine receptor A2A agonist, on the healing of chronic diabetic foot ulcers: results of a clinical trial. , 2014, The Journal of clinical endocrinology and metabolism.

[6]  H. Slade,et al.  Clinical and economic assessment of diabetic foot ulcer debridement with collagenase: results of a randomized controlled study. , 2013, Clinical therapeutics.

[7]  C. Zelen An evaluation of dehydrated human amniotic membrane allografts in patients with DFUs. , 2013, Journal of wound care.

[8]  J. Dumville,et al.  Hydrocolloid dressings for healing diabetic foot ulcers. , 2013, The Cochrane database of systematic reviews.

[9]  C. Fife,et al.  Comment on: Margolis et al. Lack of Effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation: A Cohort Study. Diabetes Care 2013;36:1961–1966 , 2013, Diabetes Care.

[10]  D. Margolis,et al.  Response to Comments on: Margolis et al. Lack of Effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation: A Cohort Study. Diabetes Care 2013;36:1961–1966 , 2013, Diabetes Care.

[11]  S. Sherlock Comment on: Margolis et al. Lack of Effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation: A Cohort Study. Diabetes Care 2013;36:1961–1966 , 2013, Diabetes Care.

[12]  Daegu Son,et al.  Treatment of Diabetic Foot Ulcer Using Matriderm In Comparison with a Skin Graft , 2013, Archives of plastic surgery.

[13]  J. Dumville,et al.  Alginate dressings for healing diabetic foot ulcers. , 2013, The Cochrane database of systematic reviews.

[14]  F. Gottrup,et al.  Randomized controlled trial on collagen/oxidized regenerated cellulose/silver treatment , 2013, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[15]  Pingsong Li,et al.  A prospective, randomized, controlled study of hyperbaric oxygen therapy: effects on healing and oxidative stress of ulcer tissue in patients with a diabetic foot ulcer. , 2013, Ostomy/wound management.

[16]  D. Margolis,et al.  Lack of Effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation , 2013, Diabetes Care.

[17]  N. Saxena,et al.  Comparative Study of Different Treatment Options of Grade III and IV Diabetic Foot Ulcers to Reduce the Incidence of Amputations , 2013, Clinics and practice.

[18]  G. Paolisso,et al.  Dipeptidyl Peptidase 4 Inhibition May Facilitate Healing of Chronic Foot Ulcers in Patients with Type 2 Diabetes , 2012, Experimental diabetes research.

[19]  N. Ullah,et al.  COMPARISON OF CONVENTIONAL PYODINE DRESSING WITH HONEY DRESSING FOR THE TREATMENT OF DIABETIC FOOT ULCERS , 2012 .

[20]  F. Wang,et al.  [Clinical study on topical bismuth subgallate/borneol (Suile) dressing for treatment of diabetic foot ulcers]. , 2012, Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery.

[21]  D. G. Armstrong,et al.  NorLeu3‐A(1–7) stimulation of diabetic foot ulcer healing: Results of a randomized, parallel‐group, double‐blind, placebo‐controlled phase 2 clinical trial , 2012, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[22]  Hak Chang,et al.  Treatment of diabetic foot ulcers using cultured allogeneic keratinocytes—A pilot study , 2012, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[23]  J. Carvalheira,et al.  Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial , 2012, PloS one.

[24]  S. Singla,et al.  Role of Epidermal Growth Factor in Healing of Diabetic Foot Ulcers , 2012, Indian Journal of Surgery.

[25]  J. Dumville,et al.  Systematic review and mixed treatment comparison: dressings to heal diabetic foot ulcers , 2012, Diabetologia.

[26]  D. Armstrong,et al.  A systematic review of interventions to enhance the healing of chronic ulcers of the foot in diabetes , 2012, Diabetes/metabolism research and reviews.

[27]  I. Harman-boehm,et al.  Efficacy of ozone-oxygen therapy for the treatment of diabetic foot ulcers. , 2011, Diabetes technology & therapeutics.

[28]  P. Bell,et al.  The effect of topical phenytoin on healing in diabetic foot ulcers: a randomized controlled trial 1 , 2011, Diabetic medicine : a journal of the British Diabetic Association.

[29]  V. Viswanathan,et al.  A pilot study on the effects of a polyherbal formulation cream on diabetic foot ulcers , 2011, The Indian journal of medical research.

[30]  G. Ghirlanda,et al.  Two-Step Autologous Grafting Using HYAFF Scaffolds in Treating Difficult Diabetic Foot Ulcers: Results of A Multicenter, Randomized Controlled Clinical Trial With Long-Term Follow-up , 2011, The international journal of lower extremity wounds.

[31]  Ya-Ju Yang,et al.  Treatment of diabetic foot ulcers: a comparative study of extracorporeal shockwave therapy and hyperbaric oxygen therapy. , 2011, Diabetes research and clinical practice.

[32]  E. Shaw,et al.  Inpatient management of diabetic foot problems: summary of NICE guidance , 2011, BMJ : British Medical Journal.

[33]  Dennis Levinson,et al.  A parallel open‐label trial to evaluate microbial cellulose wound dressing in the treatment of diabetic foot ulcers , 2011, International wound journal.

[34]  Jianpin Liu,et al.  Prospective randomized controlled study of a Chinese herbal medicine compound Tangzu Yuyang Ointment for chronic diabetic foot ulcers: a preliminary report. , 2011, Journal of ethnopharmacology.

[35]  M. Uğurlucan,et al.  Vacuum Assisted Closure Improves the Quality of Life in Patients with Diabetic Foot , 2011, Acta chirurgica Belgica.

[36]  K. Bajaj,et al.  Role of Negative Pressure Wound Therapy in Healing of Diabetic Foot Ulcers , 2011, Journal of surgical technique and case report.

[37]  H. Lehnert,et al.  Expression of Matrix-Metalloproteases in the Fluid of Chronic Diabetic Foot Wounds Treated with a Protease Absorbent Dressing , 2010, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[38]  Y. Diao,et al.  Clinical research on the bio‐debridement effect of maggot therapy for treatment of chronically infected lesions , 2010, Orthopaedic surgery.

[39]  R. Railton,et al.  Topical wound oxygen therapy in the treatment of severe diabetic foot ulcers: a prospective controlled study. , 2010, Ostomy/wound management.

[40]  Seung-Kyu Han,et al.  The treatment of diabetic foot ulcers with uncultured, processed lipoaspirate cells: A pilot study , 2010, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[41]  R. Galiano,et al.  Diabetic foot ulcers treated with becaplermin and TheraGauze, a moisture-controlling smart dressing: a randomized, multicenter, prospective analysis. , 2010, Journal of the American Podiatric Medical Association.

[42]  M. Löndahl,et al.  Hyperbaric Oxygen Therapy Facilitates Healing of Chronic Foot Ulcers in Patients With Diabetes , 2010, Diabetes Care.

[43]  Seung-Kyu Han,et al.  Treatment of Diabetic Foot Ulcers Using a Blood Bank Platelet Concentrate , 2010, Plastic and reconstructive surgery.

[44]  J. Petrofsky,et al.  Enhanced healing of diabetic foot ulcers using local heat and electrical stimulation for 30 min three times per week , 2010, Journal of diabetes.

[45]  S. Del Prato,et al.  A Randomized Controlled Trial to Examine the Efficacy and Safety of a New Super-Oxidized Solution for the Management of Wide Postsurgical Lesions of the Diabetic Foot , 2010, The international journal of lower extremity wounds.

[46]  W. Savigne,et al.  Intra‐lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo‐controlled, double‐blind study , 2009, International wound journal.

[47]  Seung-Kyu Han,et al.  Efficacy and Safety of Fresh Fibroblast Allografts in the Treatment of Diabetic Foot Ulcers , 2009, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[48]  K. Urabe,et al.  Clinical efficacy of basic fibroblast growth factor (bFGF) for diabetic ulcer. , 2009, European journal of dermatology : EJD.

[49]  A. Younger,et al.  Outcome of Transmetatarsal Amputations in Diabetics Using Antibiotic Beads , 2009, Foot & ankle international.

[50]  Ryan T. Crews,et al.  Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study , 2009, International wound journal.

[51]  S. Tafuri,et al.  The management of neuropathic ulcers of the foot in diabetes by shock wave therapy , 2009, BMC musculoskeletal disorders.

[52]  Ching‐Jen Wang,et al.  Extracorporeal shockwave treatment for chronic diabetic foot ulcers. , 2009, The Journal of surgical research.

[53]  M. Edmonds Apligraf in the Treatment of Neuropathic Diabetic Foot Ulcers , 2009, The international journal of lower extremity wounds.

[54]  H. L. Lee,et al.  Maggot debridement therapy with Lucilia cuprina: a comparison with conventional debridement in diabetic foot ulcers , 2009, International wound journal.

[55]  G. Naughton,et al.  A metabolically active human dermal replacement for the treatment of diabetic foot ulcers. , 2008, Artificial organs.

[56]  B. Kulah,et al.  Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers. , 2008, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[57]  A. M. Jacobs,et al.  Evaluation of Bensal HP for the Treatment of Diabetic Foot Ulcers , 2008, Advances in skin & wound care.

[58]  J. Llobera,et al.  Treatment of chronic diabetic foot ulcers with bemiparin: a randomized, triple‐blind, placebo‐controlled, clinical trial , 2008, Diabetic medicine : a journal of the British Diabetic Association.

[59]  S. Mahmoud,et al.  Split-skin graft in the management of diabetic foot ulcers. , 2008, Journal of wound care.

[60]  W. Jeffcoate,et al.  A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes , 2008, Diabetes/metabolism research and reviews.

[61]  W. Caputo,et al.  A prospective randomised controlled clinical trial comparing hydrosurgery debridement with conventional surgical debridement in lower extremity ulcers , 2008, International wound journal.

[62]  P. Blume,et al.  Comparison of Negative Pressure Wound Therapy Using Vacuum-Assisted Closure With Advanced Moist Wound Therapy in the Treatment of Diabetic Foot Ulcers , 2008, Diabetes Care.

[63]  A. R. Sulaiman,et al.  A comparative study between honey and povidone iodine as dressing solution for Wagner type II diabetic foot ulcers. , 2008, The Medical journal of Malaysia.

[64]  P. Gloviczki,et al.  Improving limb salvage in critical ischemia with intermittent pneumatic compression: a controlled study with 18-month follow-up. , 2008, Journal of vascular surgery.

[65]  M. Rahman,et al.  Neuropharmacological effects of Peperomia pellucida leaves in mice , 2008 .

[66]  P. Leung,et al.  Limb salvage in extensive diabetic foot ulceration: an extended study using a herbal supplement. , 2008, Hong Kong medical journal = Xianggang yi xue za zhi.

[67]  M. Mars,et al.  Compressed air massage hastens healing of the diabetic foot. , 2008, Diabetes technology & therapeutics.

[68]  W. Jeffcoate,et al.  Randomized, controlled, single-blind study on use of autologous keratinocytes on a transfer dressing to treat nonhealing diabetic ulcers. , 2007, Regenerative medicine.

[69]  G. Georgiadis,et al.  Synergistic action of protease-modulating matrix and autologous growth factors in healing of diabetic foot ulcers. A prospective randomized trial. , 2007, Journal of diabetes and its complications.

[70]  R. Frykberg,et al.  Negative-pressure wound therapy and diabetic foot amputations: a retrospective study of payer claims data. , 2007, Journal of the American Podiatric Medical Association.

[71]  F. J. Aragón-Sánchez,et al.  [Randomized comparative trial of a collagen/oxidized regenerated cellulose dressing in the treatment of neuropathic diabetic foot ulcers]. , 2007, Cirugia espanola.

[72]  J. L. Lázaro-Martínez,et al.  Estudio aleatorizado y comparativo de un apósito de colágeno y celulosa oxidada regenerada en el tratamiento de úlceras neuropáticas de pie diabético , 2007 .

[73]  A. Supe,et al.  Immunomodulatory role of Tinospora cordifolia as an adjuvant in surgical treatment of diabetic foot ulcers: a prospective randomized controlled study. , 2007, Indian journal of medical sciences.

[74]  M. Spraul,et al.  Prospective randomized controlled study of Hydrofiber® dressing containing ionic silver or calcium alginate dressings in non‐ischaemic diabetic foot ulcers , 2007, Diabetic medicine : a journal of the British Diabetic Association.

[75]  Stephen A. Brigido,et al.  The use of an acellular dermal regenerative tissue matrix in the treatment of lower extremity wounds: a prospective 16‐week pilot study , 2006, International wound journal.

[76]  The use of an acellular dermal regenerative tissue matrix in the treatment of lower extremity wounds: a prospective 16‐week pilot study , 2006 .

[77]  A. Smit,et al.  Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial. , 2006, Human Gene Therapy.

[78]  V. Driver,et al.  A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers. , 2006, Ostomy/wound management.

[79]  D. Armstrong,et al.  Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial , 2005, The Lancet.

[80]  W. Tom,et al.  The effect of short-contact topical tretinoin therapy for foot ulcers in patients with diabetes. , 2005, Archives of dermatology.

[81]  Mustafa Sengezer,et al.  The cell based dressing with living allogenic keratinocytes in the treatment of foot ulcers: a case study. , 2005, British journal of plastic surgery.

[82]  B. Larijani,et al.  Efficacy of topical epidermal growth factor in healing diabetic foot ulcers , 2005 .

[83]  Z. Han,et al.  Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. , 2005, Diabetes care.

[84]  W. Ennis,et al.  Ultrasound therapy for recalcitrant diabetic foot ulcers: results of a randomized, double-blind, controlled, multicenter study. , 2005, Ostomy/wound management.

[85]  D. Armstrong,et al.  Efficacy of fifth metatarsal head resection for treatment of chronic diabetic foot ulceration. , 2005, Journal of the American Podiatric Medical Association.

[86]  R. Frykberg,et al.  Randomized Clinical Trial Comparing OASIS Wound Matrix to Regranex Gel for Diabetic Ulcers , 2005, Advances in skin & wound care.

[87]  D. Armstrong,et al.  Maggot therapy in "lower-extremity hospice" wound care: fewer amputations and more antibiotic-free days. , 2005, Journal of the American Podiatric Medical Association.

[88]  D. Armstrong,et al.  Clinical efficacy of the first metatarsophalangeal joint arthroplasty as a curative procedure for hallux interphalangeal joint wounds in patients with diabetes. , 2003, Diabetes care.

[89]  G. Seabrook,et al.  A Prospective Randomized Evaluation of Negative-pressure Wound Dressings for Diabetic Foot Wounds , 2003, Annals of vascular surgery.

[90]  M. Pinget,et al.  Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. , 2003, Diabetes care.

[91]  M. Tsang,et al.  Human epidermal growth factor enhances healing of diabetic foot ulcers. , 2003, Diabetes care.

[92]  W. Marston,et al.  The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. , 2003, Diabetes care.

[93]  E. Masson,et al.  The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. , 2003, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[94]  R. Sherman,et al.  Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy. , 2003, Diabetes care.

[95]  V. Falanga,et al.  Debridement performance index and its correlation with complete closure of diabetic foot ulcers , 2002, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[96]  A. Veves,et al.  A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers. , 2002, Archives of surgery.

[97]  J. Martini,et al.  Efficacy and tolerance of calcium alginate versus vaseline gauze dressings in the treatment of diabetic foot lesions. , 2002, Diabetes & metabolism.

[98]  J. Szor,et al.  Lessons learned in research: an attempt to study the effects of magnetic therapy. , 2002, Ostomy/wound management.

[99]  M. Kotian,et al.  Topical phenytoin in diabetic ulcers: a double blind controlled trial. , 2001, Indian journal of medical sciences.

[100]  S. Guler,et al.  Effects of granulocyte‐colony stimulating factor in the treatment of diabetic foot infection , 2001, Diabetes, obesity & metabolism.

[101]  D. Armstrong,et al.  Electric stimulation as an adjunct to heal diabetic foot ulcers: a randomized clinical trial. , 2001, Archives of physical medicine and rehabilitation.

[102]  M. Romanelli,et al.  Sodium carboxyl‐methyl‐cellulose dressings in the management of deep ulcerations of diabetic foot , 2001, Diabetic medicine : a journal of the British Diabetic Association.

[103]  P. Benedetti,et al.  Randomized Prospective Controlled Trial of Recombinant Granulocyte Colony-Stimulating Factor as Adjunctive Therapy for Limb-Threatening Diabetic Foot Infection , 2001, Antimicrobial Agents and Chemotherapy.

[104]  D. Margolis,et al.  Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers. , 2001, Diabetes care.

[105]  David G Armstrong,et al.  Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. , 2001, Diabetes care.

[106]  D. Armstrong,et al.  Improvement in healing with aggressive edema reduction after debridement of foot infection in persons with diabetes. , 2000, Archives of surgery.

[107]  M. Heng,et al.  Enhanced healing and cost-effectiveness of low-pressure oxygen therapy in healing necrotic wounds: a feasibility study of technology transfer. , 2000, Ostomy/wound management.

[108]  J. Feng,et al.  [Clinical study of various growth factors on the improvement of impaired healing ulcers in patients with diabetic disease]. , 1999, Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery.

[109]  J. Seeley,et al.  Diabetic foot ulcerations. A controlled, randomized comparison of two moist wound healing protocols: Carrasyn Hydrogel Wound dressing and wet-to-moist saline gauze. , 1998, Advances in wound care : the journal for prevention and healing.

[110]  M. Romanelli,et al.  Conservative surgical approach versus non‐surgical management for diabetic neuropathic foot ulcers: a randomized trial , 1998, Diabetic medicine : a journal of the British Diabetic Association.

[111]  J. Giurini,et al.  Evaluation of a collagen-alginate wound dressing in the management of diabetic foot ulcers. , 1998, Advances in wound care : the journal for prevention and healing.

[112]  J. Smiell,et al.  Efficacy and Safely of a Topical Gel Formulation of Recombinant Human Platelet-Derived Growth Factor-BB (Becaplermin) in Patients With Chronic Neuropathic Diabetic Ulcers: A phase III randomized placebo-controlled double-blind study , 1998, Diabetes Care.

[113]  M. Edmonds,et al.  Randomised placebo-controlled trial of granulocyte-colony stimulating factor in diabetic foot infection , 1997, The Lancet.

[114]  L. Baker,et al.  Effects of Electrical Stimulation on Wound Healing in Patients With Diabetic Ulcers , 1997, Diabetes Care.

[115]  A. Morabito,et al.  Adjunctive Systemic Hyperbaric Oxygen Therapy in Treatment of Severe Prevalently Ischemic Diabetic Foot Ulcer: A randomized study , 1996, Diabetes Care.

[116]  T. File,et al.  Can aggressive treatment of diabetic foot infections reduce the need for above-ankle amputation? , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[117]  D. Steed,et al.  Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic Ulcer Study Group. , 1996, Journal of the American College of Surgeons.

[118]  J. Apelqvist,et al.  Cavity foot ulcers in diabetic patients: a comparative study of cadexomer iodine ointment and standard treatment. An economic analysis alongside a clinical trial. , 1996, Acta dermato-venereologica.

[119]  J. Ricotta,et al.  Use of Dermagraft, a Cultured Human Dermis, to Treat Diabetic Foot Ulcers , 1996, Diabetes Care.

[120]  J. Bringer,et al.  Effect of Topical Basic Fibroblast Growth Factor on the Healing of Chronic Diabetic Neuropathic Ulcer of the foot: A pilot, randomized, double-blind, placebo-controlled study , 1995, Diabetes Care.

[121]  L. Quinn,et al.  Clinical Evaluation of a Semipermeable Polymeric Membrane Dressing for the Treatment of Chronic Diabetic Foot Ulcers , 1994, Diabetes Care.

[122]  G. A. Holloway,et al.  Randomized Prospective Double-Blind Trial in Healing Chronic Diabetic Foot Ulcers: CT-102 activated platelet supernatant, topical versus placebo , 1992, Diabetes Care.

[123]  A. Supe,et al.  Hyperbaric oxygen therapy in diabetic foot. , 1992, Journal of postgraduate medicine.

[124]  M. Muthukumarasamy,et al.  Topical Phenytoin in Diabetic Foot Ulcers , 1991, Diabetes Care.

[125]  J. Apelqvist,et al.  Topical treatment of necrotic foot ulcers in diabetic patients: a comparative trial of DuoDerm and MeZinc , 1990, The British journal of dermatology.

[126]  R. Adkins,et al.  Randomized Controlled Trial of Topical Hyperbaric Oxygen for Treatment of Diabetic Foot Ulcers , 1988, Diabetes Care.

[127]  H. MunroB The cost and efficacy of two wound treatments , 2017 .

[128]  A. Chitale,et al.  Pentoxifylline: a new armamentarium in diabetic foot ulcers. , 2014, Journal of clinical and diagnostic research : JCDR.

[129]  J. Dumville,et al.  Hydrogel dressings for healing diabetic foot ulcers. , 2011, The Cochrane database of systematic reviews.

[130]  J. Dumville,et al.  Foam dressings for healing diabetic foot ulcers. , 2011, The Cochrane database of systematic reviews.

[131]  S. Ninkovic,et al.  Use of Vacuum Assisted Closure Therapy in the Treatment of Diabetic Foot Wounds , 2010 .

[132]  W. Jeffcoate,et al.  Randomised controlled trial of the use of three dressing preparations in the management of chronic ulceration of the foot in diabetes. , 2009, Health technology assessment.

[133]  C. Manterola,et al.  Negative-pressure wound therapy versus standard wound dressing in the treatment of diabetic foot amputation. A randomised controlled trial ☆ , 2009 .

[134]  C. Manterola,et al.  [Negative-pressure wound therapy versus standard wound dressing in the treatment of diabetic foot amputation. A randomised controlled trial]. , 2009, Cirugia espanola.

[135]  K. Aikimbaev,et al.  Effects of iloprost (a prostacyclin analogue) on the endothelial dysfunction and foot ulcers in diabetic patients with peripheral arterial disease , 2008 .

[136]  Farhadi,et al.  Effects of intravenous Semelil (ANGIPARSTM) on diabetic foot ulcers healing: A multicenter clinical trial , 2008 .

[137]  A. Rodgers,et al.  Honey as a topical treatment for wounds. , 2008, The Cochrane database of systematic reviews.

[138]  C. Fife,et al.  Thrombin peptide Chrysalin® stimulates healing of diabetic foot ulcers in a placebo‐controlled phase I/II study , 2007, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[139]  F. Ghiasi,et al.  Effects of vacuum-compression therapy on healing of diabetic foot ulcers: randomized controlled trial. , 2007, Journal of rehabilitation research and development.

[140]  R. Kirsner,et al.  Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study. , 2007, American journal of surgery.

[141]  J. Biundo Integrating the Results of Phase IV (Postmarketing) Clinical Trial With Four Previous Trials Reinforces the Position that Regranex (Becaplermin) Gel 0.01% Is an EffectiveAdjunct to the Treatment of Diabetic Foot Ulcers , 2005 .

[142]  D. Istomin,et al.  [Complex treatment of patients with the diabetic foot]. , 2004, Klinicheskaia meditsina.

[143]  Paisarn Puttirutvong Meshed skin graft versus split thickness skin graft in diabetic ulcer coverage. , 2004, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.

[144]  Chiglashvili Ds,et al.  Complex treatment of patients with the diabetic foot , 2004 .

[145]  O. Alvarez,et al.  Effect of noncontact normothermic wound therapy on the healing of neuropathic (diabetic) foot ulcers: an interim analysis of 20 patients. , 2003, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[146]  T. Kästenbauer,et al.  Evaluation of granulocyte-colony stimulating factor (Filgrastim) in infected diabetic foot ulcers , 2002, Diabetologia.

[147]  S. McCallon,et al.  Vacuum-assisted closure versus saline-moistened gauze in the healing of postoperative diabetic foot wounds. , 2000, Ostomy/wound management.

[148]  D. Steed Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group. , 1995, Journal of vascular surgery.

[149]  G. Deitrick,et al.  A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report. , 1992, Journal of vascular surgery.

[150]  J. Glover A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report. , 1992, Journal of vascular surgery.

[151]  C. Di Mauro,et al.  Lyophilized collagen in the treatment of diabetic ulcers. , 1991, Drugs under experimental and clinical research.

[152]  C. P. Cangialosi Synthetic skin. A new adjunct in the treatment of diabetic ulcers. , 1982, Journal of the American Podiatry Association.

[153]  Cangialosi Cp Synthetic skin. A new adjunct in the treatment of diabetic ulcers. , 1982 .