Treatment of recalcitrant venous leg ulcers with autologous keratinocytes in fibrin sealant: A multinational randomized controlled clinical trial

In a multicenter trial, the effect of a commercially available combination of autologous keratinocytes (3-6 x 10(6)/mL) with fibrin sealant (Tissucol Duo S Immuno, Baxter Hyland Immuno) on the healing of recalcitrant venous leg ulcers (duration >3 months) was compared with standard care. The primary endpoint was time to healing, and the secondary endpoint was number of healed ulcers in both groups. Both groups received compression therapy with short-stretch bandages. Forty-four (38.3%) of the 116 patients who had BioSeed-S treatment achieved complete healing of the target ulcer compared with 24 (22.4%) of 109 patients who received standard treatment. The advantage for treatment with BioSeed-S over standard treatment was statistically significant (chi-square test: p=0.0106). Time to complete healing of ulcers: the log-rank test for equality over strata revealed a superiority of treatment with BioSeed-S+compression (median: 176 days) over compression+standard care (median >201 days) (p<0.0001). This study, to date the largest multicenter study with autologous keratinocytes, provides evidence for its efficacy in the treatment of patients with therapy-resistant chronic venous leg ulcers.     

Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers

OBJECTIVES: Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid. METHODS: This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment. RESULTS: Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (P =.94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment. CONCLUSION: Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.     

Autologous cultured keratinocytes on porcine gelatin microbeads effectively heal chronic venous leg ulcers.

We have established a specific bioreactor microcarrier cell culture system using porcine gelatin microbeads as carriers to produce autologous keratinocytes on a large scale. Moreover, we have shown that autologous keratinocytes can be cultured on porcine collagen pads, thereby forming a single cell layer. The objective of this study was to compare efficacy and safety of autologous cultured keratinocytes on microbeads and collagen pads in the treatment of chronic wounds. Fifteen patients with recalcitrant venous leg ulcers were assigned to three groups in a single-center, prospective, uncontrolled study: five underwent a single treatment with keratinocyte monolayers on collagen pads (group 1); another five received a single grafting with keratinocyte-microbeads (group 2); and the last five received multiple, consecutive applications of keratinocyte-microbeads 3 days apart (group 3). All patients were followed for up to 12 weeks. By 12 weeks, there was a mean reduction in the initial wound area of 50, 83, and 97 percent in the three groups, respectively. The changes in wound size were statistically significant between the first and third groups (p= 0.0003). Keratinocyte-microbeads proved to be more effective than keratinocyte monolayers on collagen pads when the former were applied every 3 days. Rapid availability within 10-13 days after skin biopsy and easy handling represent particular advantages.     

Autologous platelet‐rich fibrin matrix as cell therapy in the healing of chronic lower‐extremity ulcers

A novel autologous platelet‐rich fibrin matrix membrane (PRFM) was assessed for the ability to facilitate healing in patients with chronic lower‐extremity ulcers. Preliminary data are presented from a prospective trial (n=21). Twelve patients were identified with 17 venous leg ulcers (VLU) and nine bearing 13 nonvenous lower‐extremity ulcers. Before enrollment, the patients were evaluated for vascular status and received appropriate surgical intervention to optimize arterial and venous circulatory status. None of the ulcers had responded to a variety of standard treatments from 4 months to 53 years. Initial ulcer size ranged from 0.7 to 65 cm² (mean, 11.2 cm²). Each PRFM‐treated patient received up to three applications of either a 35 or 50 mm fenestrated membrane, depending on initial ulcer size. The primary endpoints were percent and rate of complete closure as measured by digital photography, computerized planimetery, and clinical examination. Patients were followed weekly for 12 weeks with a follow‐up visit at 16 weeks. At each 4‐week interval, the extent of healing was assessed, and those patients with >50% reduction in wound area were allowed to continue to complete closure. Patients with <50% closure received repeated applications. Complete closure was achieved in 66.7% of the VLU patients (64.7% of treated ulcers) in 7.1 weeks (median, 6 weeks) with an average of two applications per patient. Forty‐four percent complete closure was seen with non‐VLU patients (31% of treated ulcers). From the results of this small‐scale pilot study, PRFM shows significant potential for closing of chronic leg ulcers.     

Treatment of burns and chronic wounds using a new cell transfer dressing for delivery of autologous keratinocytes

This study describes a new methodology for delivering cultured autologous keratinocytes to wounds on a sterile medical grade polymer coated with a chemically defined plasma polymerised functional surface containing 20% carboxylic acid (referred to as PPS). Seven patients (two acute major burns and five chronic non-healing wounds) were treated with applications of autologous keratinocytes delivered on a 6 cm diameter medical grade polymer disc whose surface was functionalised by PPS. For initial keratinocyte expansion a split-thickness skin biopsy was taken from each patient followed by keratinocyte isolation and expansion and, where required for repeated applications, freezing down of keratinocytes. After expansion, cells were cultured on the PPS for 2 days then the PPS with cells was inverted onto the patients wound bed to allow cell transfer to wound beds. For two burns patients transfer of cells from PPS onto donor sites was seen for both patients and it appeared to facilitate healing of grafted burns wounds. For five patients with intractable chronic wounds (with nine ulcers in total) repeated applications of cells resulted in complete healing in 5/9 ulcers with a major reduction in ulcer size for all other (4/9) ulcers. This reduction in ulcer size improved the wound conditions for two of these patients such that they were then considered suitable for conventional grafting and orthopaedic surgery respectively. In conclusion, PPS delivery of autologous cells is a promising approach for acute burns injuries and chronic wounds.This paper is dedicated to the memory of Mr Archibald Newman (Patient 3) who sadly died in January 2005.     

Locomotion of human skin keratinocytes on polystyrene, fibrin, and collagen substrata and its modification by cell-to-cell contacts

Epithelial wound repair assures the recovery of the epithelial barrier after wounding. During wound healing epithelial cells migrate to cover the wound surface. The presented experiments were carried out to compare the migration of human keratinocytes from primary and secondary culture on polystyrene, collagen, and fibrin glue used in clinical techniques. The images of migrating keratinocytes were recorded and analyzed using computer-aided methods. The results show that the character of the substrate strongly affects the speed and turning behavior of keratinocytes locomoting over it. The highest motile activity of human skin keratinocytes was found on fibrin glue substratum. It was found that locomotion of freely moving isolated cells was much faster than that of cell sheets. The autologous keratinocytes cultured in vitro were applied with fibrin glue to cover trophic wounds. The transplantation of human autologous keratinocyte suspension in fibrin glue upon long-lasting trophic wounds appeared to induce rapid and permanent wound healing.     

Treatment of venous ulcers with bone marrow-impregnated collagen matrix

Bone marrow attracted our attention as a potentially beneficial material for the treatment of wounds, because it contains multipotential progenitor cells and produces growth factors. We impregnated autologous bone marrow cells on to a collagen matrix that had been used for the treatment of chronic wounds. The bone marrow-impregnated collagen matrix was then as a biomaterial scaffold for the treatment of wounds. This study was designed with the aim of clinically evaluating the effects of bone marrow-impregnated collagen matrix on wound healing of venous ulcers. We applied the matrix in 15 patients with chronic venous ulcers, and evaluated the transcutaneous oxygen tension (TcPO(2)) and vascular density. The application of the matrix induced healthy granulation tissue. All patients were given a split-thickness skin graft on to the induced granulation tissue, and have remained free from complications for more than eight months since the treatment. The mean (SD) vascular density at the ulcer base increased after the treatment (before 0.011 (0.006) mm(2)/mm(2), after 0.064 (0.036) mm(2)/mm(2), p < 0.001). The periwound TcPO(2) values tended to increase (before 17.1 (12.7) mmHg, after 30.6 (13.4) mmHg, p < 0.001). Our results have shown the efficacy of bone marrow-impregnated collagen matrix for the treatment of intractable venous ulcers.     

Effect of oxidised regenerated cellulose/collagen matrix on proteases in wound exudate of patients with chronic venous ulceration

Oxidised regenerated cellulose/collagen matrix (ORC/collagen matrix) modifies wound microenvironments by binding and inactivating excess levels of proteases such as elastase, plasmin and gelatinases in wound exudates. To compare levels of the gelatinases matrix metalloproteinase 2 (MMP-2), elastase and plasmin in wound exudates collected from chronic venous insufficiency patients with venous leg ulcers treated with either an ORC/collagen matrix or a standard control therapy. During a 12-week treatment period, wound exudate samples were obtained from a control group of 10 patients treated with a hydrocolloid dressing and a treatment group of 17 patients treated with a combination of ORC/collagen matrix and hydrocolloid dressing. On admission and days 5, 14 and every subsequent 14th day, ulcers were photographed to determine healing rate and changes in ulcer appearance, and MMP-2 concentration and the gelatinase, elastase and plasmin activities were analysed from wound exudates. The patients treated with ORC/collagen matrix showed a significant decrease in elastase, plasmin and gelastinase activity as compared with the control group, with no significant difference in the MMP-2 concentrations between the two groups. The results show a significant and immediate reduction in protease activity in wound exudates from venous leg ulcers treated with ORC/collagen.     

Tapping into the Influence of Keratinocyte Allografts and Biocenosis on Healing of Chronic Leg Ulcers: Split-Ulcer Controlled Pilot Study

BACKGROUND: Cultured keratinocytes may represent an alternative therapy aiming at boosting leg ulcer healing. There is no evidence-based study comparing objectively the healing rate of split-ulcer portions covered or not covered by cultured keratinocytes. OBJECTIVE: To assess the effect of cultured keratinocytes on the healing rate of leg ulcers. METHOD: Five applications of fresh (cela, XCELLentis, Ghent, Belgium) or frozen (CryoCeal, XCELLentis) cultured allogeneic keratinocytes were performed at weekly intervals to treat large leg ulcers (mean diameter > 5 cm) in four patients. A split-ulcer study was designed to secure a control area covered only by petrolatum gauze. Clinical, planimetric, bacteriologic, and immunohistologic assessments of the keratinocyte-treated and control parts of the ulcers were performed. RESULTS: Compared with controls, planimetry revealed a beneficial effect afforded by cryopreserved cultured keratinocytes on the ulcer healing rate of two of four ulcers (+12 and 81%). The healing effect was obtained on the ulcers associated with the lowest bacterial load. Cultured keratinocytes did not qualitatively and quantitatively modify the ulcer biocenosis. They did not affect the number of any type of inflammatory cells present in the granulation tissue (type I dermal dendrocytes, macrophages, T lymphocytes, granulocytes). No specific side effect of cultured keratinocytes was evidenced. CONCLUSION: In this small case series, it appears that cultured allogeneic keratinocytes may be helpful in the healing process of venous leg ulcers. However, a clean wound with reduced bacterial load seems to be the prerequisite condition for obtaining a beneficial effect.     

Changes in the extracellular matrix surrounding human chronic wounds revealed by 2‐photon imaging

Chronic wounds are a growing problem worldwide with no effective therapeutic treatments available. Our objective was to understand the composition of the dermal tissue surrounding venous leg ulcers and diabetic foot ulcers (DFU). We used novel 2‐photon imaging techniques alongside classical histology to examine biopsies from the edges of two common types of chronic wound, venous leg ulcers and DFU. Compared to normal intact skin, we found that collagen levels are significantly reduced throughout the dermis of venous leg ulcer biopsies and DFU, with a reduction in both fibril thickness and abundance. Both wound types showed a significant reduction in elastin in the upper dermis, but in DFU, the loss was throughout the dermis. Loss of extracellular matrix correlated with high levels of CD68‐ and CD18‐positive leukocytes. 2‐photon imaging of the extracellular matrix in the intact tissue surrounding a chronic wound with a hand‐held device may provide a useful clinical indicator on the healing progression or deterioration of these wounds.     

Management of leg ulcers in patients with rheumatoid arthritis or systemic sclerosis: the importance of concomitant arterial and venous disease

PURPOSE: We assessed the etiology and the prevalence of peripheral arterial and venous disease in leg ulcers in patients with rheumatoid arthritis and systemic sclerosis and analyzed the outcome after treatment of macrovascular disease. METHODS: A clinical study on 15 consecutive patients with chronic leg ulcers in collagen vascular disease (nine patients with rheumatoid arthritis, six patients with systemic sclerosis) was carried out in a referral center. Angiography was used when the ankle-arm index was less than 0.8; venography was used when venous reflux was detectable by means of a hand-held Doppler examination. Therapies included percutaneous transluminal angioplasty (seven patients), femoropopliteal bypass grafting surgery (one patient), saphenectomy of the greater saphenous vein (six patients), and split skin graft (11 patients). RESULTS: All patients with rheumatoid arthritis exhibited a multifactorial etiology of their ulcers: four of nine patients had peripheral arterial disease, and five of nine patients had venous insufficiency. In one of these patients, arterial and venous disease was combined. Five of six patients with systemic sclerosis exhibited a multifactorial etiology of their ulcers: three of six patients had peripheral arterial disease, and three of six patients had venous insufficiency. One of these patients had both arterial and venous disease. In patients with rheumatoid arthritis, healing was achieved in six of nine patients, and marked improvement occurred in two of nine patients. A below-knee amputation was necessary in one patient with rheumatoid vasculitis. In patients with systemic sclerosis, healing was achieved in three of six patients, and marked improvement occurred in the other three patients. CONCLUSION: Most leg ulcers in patients with rheumatoid arthritis and systemic sclerosis disclose a multifactorial etiology. Relevant arterial and venous disease can be found in approximately half the patients. Our study suggests that revascularization and vein surgery improve the healing of leg ulcers in patients with collagen vascular disease. A prospective trial is now required to confirm these results.     

Induction of MMP-1, MMP-3 and TIMP-1 in normal dermal fibroblasts by chronic venous leg ulcer wound fluid*

In the wound bed of chronic venous leg ulcers, an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may cause excessive proteolysis and impair wound granulation. Soluble mediators in the wound environment may be responsible for this imbalance. The in vitro effect of wound fluid from venous leg ulcers on dermal fibroblast production of MMP-1, MMP-3 and TIMP-1 was compared with the effect of acute wound fluid from two different sources: fluid from post-mastectomy axillary drains and fluid from skin graft donor sites. Significantly higher MMP-1 and MMP-3 levels were induced by chronic venous leg ulcer wound fluid compared with both types of acute wound fluid (P < 0.005). Chronic venous ulcer wound fluid reduced TIMP-1 protein levels significantly more than acute graft fluid (P < 0.05). Venous ulcer wound fluid significantly increased MMP-1 and MMP-3 production in dermal fibroblasts and reduced TIMP-1 production, confirming that mediators in the leg ulcer microenvironment can potentially induce excessive proteolysis in the ulcer dermis by altering the balance between MMPs and TIMPs. Inflammatory mediators including interleukin-1beta and tumour necrosis factor-alpha can induce these MMPs. Further work is required to confirm the factors responsible for the induction of a high MMP and low TIMP profile in fibroblasts by venous ulcer wound fluid.     

Treatment of leg ulcers with split skin grafts: early and late results.

Sixty patients (mean age 73.5 years) with 88 leg ulcers that had not responded to conservative treatment had split skin grafts applied at the Department of Plastic Surgery, Link?ping, Sweden. Of 51 venous leg ulcers 45 (88%) healed after a mean of 15 days (range 5-30); and 13 (62%) of the 21 arterial ulcers healed after a mean of 18 days (range 8-30). Additional skin grafting was done on nine of the venous and on three of the arterial ulcers. Twenty-two (49%) of the healed venous ulcers recurred after a mean of four months while only two (15%) of the healed arterial ulcers recurred after a mean of 10 months. At late follow up after a mean of four years 18 of the patients were dead and 10 had had the leg in question amputated. Of the 34 patients still alive who had not had amputations, 31 were investigated at open ward or interviewed by telephone and 23 patients were examined with colour duplex scan. Seven of these patients had open leg ulcers. At duplex scan six patients had no venous or arterial insufficiency that could cause a leg ulcer. Of 16 patients with venous insufficiency 10 patients had only an inadequate superficial system. The mean cost for treating one leg ulcer by skin grafting is estimated at SEK 89000 (US$11125). We conclude that leg ulcers often heal with skin grafting but that venous ulcers often recur. To reduce the recurrence rate we suggest a better preoperative aetiological evaluation and improved postoperative treatment with a compression bandage.     

The impact of differential expression of extracellular matrix metalloproteinase inducer, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2 and PDGF-AA on the chronicity of venous leg ulcers.

INTRODUCTION: Alteration in the expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase-2 (MMP-2), tissue inhibitors of matrix metalloproteinases (TIMP-2) and platelet derived growth factor (PDGF-AA) may contribute to poor healing in venous leg ulcers. AIM: The aim of this study is to determine the expression of EMMPRIN, MMP-2, TIMP-2 and PDGF-AA in the ulcer exudates and perivascular tissue of healing and non-healing chronic venous ulcers. PATIENTS, MATERIALS AND METHODS: Forty patients with chronic venous ulcers were included in this study, with a mean age of 60 years. Eleven patients were males and 29 were females. All patients had normal ankle brachial index and a venous ulcer of at least 8 weeks duration. Immuno-histochemistry using monoclonal antibodies to PDGF-AA, MMP-2, TIMP-2 and EMMPRIN was carried out on paraffin embedded punch biopsy skin specimens from the ulcer edge. Enzyme linked immunosorbent assay for PDGF, MMP-2 and TIMP-2 were carried out on wound fluids collected from patients. The ulcer size and character at the initial assessment and after 8 weeks were assessed to determine the status of ulcer healing. RESULTS: No significant difference was seen in the expression of TIMP-2, MMP-2 and EMMPRIN between the two groups. However, in the non-healing group high levels of MMP-2 and low levels of TIMP-2 in the wound fluid suggest a strong correlation of these two markers in the state of healing. Analysis of wound fluid by ELISA demonstrated high PDGF-AA in the healing group (p = 0.021). Significantly increased levels of PDGF-AA (p<0001) was noted in the perivascular area on immuno-histochemistry of healing ulcers. These data suggest that PDGF-AA plays an important role in healing of venous ulcers. CONCLUSION: Non-healing venous ulcers are associated with greater activity MMP-2 activity. The ratio of MMPs to their inhibitors TIMPs, dictate the rate of healing of the ulcers. PDGF-AA activity is associated with ulcer healing, though the mechanism is unclear. EMMPRIN expression in chronic venous ulcers probably parallels the chronicity of the condition rather than propagate it. However, further studies with larger samples are needed.     

Synergistic effect of keratinocyte transplantation and epidermal growth factor delivery on epidermal regeneration

Both keratinocyte transplantation and epidermal growth factor (EGF) delivery stimulate epidermal regeneration. In this study, we hypothesized that the combined therapy of keratinocyte transplantation and EGF delivery accelerates epidermal regeneration compared to the single therapy of either keratinocyte transplantation or EGF delivery. To test this hypothesis, we utilized fibrin matrix as a keratinocyte/EGF delivery vehicle for epidermal regeneration. Full-thickness wounds were created on the dorsum of athymic mice, and human keratinocytes and EGF in fibrin matrix were sprayed onto the wounds to regenerate epidermal layers (group 1). As controls, human keratinocytes in fibrin matrix (group 2), EGF in fibrin matrix (group 3), or fibrin matrix alone (group 4) was sprayed onto the wounds. Spraying keratinocytes suspended in fibrin matrix did not affect the keratinocyte viability, as the cell viabilities before and after spraying were not different. EGF was released from fibrin matrix for 3 days. The wounds were analyzed with histology and immunohistochemistry at 1 and 3 weeks after treatments. Compared with the control groups, initial wound closure rate was highest in group 1. Histological analyses indicated that group 1 exhibited faster and better epidermal regeneration than the other groups. Immunohistochemical analyses showed that regenerated epithelium in groups 1 and 2 stained positively for human involucrin at 3 weeks, whereas the tissue sections of the groups 3 and 4 stained negatively. Human laminin was detected at the dermal-epidermal junction of the regenerated tissues in groups 1 and 2 at 3 weeks and was not detected in groups 3 and 4. The epidermal thickness of the regenerated tissues in group 1 was significantly thicker than that of the other groups at all time points. These results suggest that the combined therapy of keratinocyte transplantation and EGF delivery is more efficacious for epidermal regeneration than each separate therapy alone.     

Standardised method of surgical treatment of chronic leg ulcers.

Healing and recurrence rates were compared in leg ulcers of different aetiology in 385 patients with 406 chronic leg ulcers. Standard treatment was excision of the ulcer followed by meshed split-skin grafting and correction of superficial venous insufficiency in the area. The median age of the patients was 75 years (range 16-95). After one year 345 patients with 357 leg ulcers were alive. Overall healing rate was 64% (227 in 357 legs) after one year. The best results were achieved in traumatic ulcers (31 in 36 ulcers) and worst for the arterial ulcers (4 in 20 ulcers). Recurrence rate in venous and venous/ischaemic ulcers was 14% (33 in 235 legs) and 8% (n=3) in the traumatic ulcers. Vasculitic ulcers tend to recur 59% (n=10), but the graft does relieve pain.     

Tissue and urinary haemosiderin in chronic leg ulcers.

OBJECTIVE: The aim of this study was to assess the relationship between urinary and tissue haemosiderin in chronic leg ulcers, and its value as a diagnostic test for venous ulceration. METHODS: 45 patients with chronic leg ulcers were recruited to the study (24 venous, 6 ischaemic, 6 lymphoedematous, 5 rheumatoid and 4 sickle cell). Punch biopsy of the ulcer edge was taken and early morning urine samples were collected. Positive Prussian-blue urinary haemosiderin granules were measured with a haemocytometer following Perls' staining. The percentage area of histological section staining positively with Perls' was measured using image analysis. RESULTS: 84 urine samples and 46 ulcer biopsies were collected. Urinary haemosiderin was present in 92% of venous ulcer patients, but was absent in the ischaemic ulcer patients (p<0.0001). Significantly more urinary haemosiderin granules were detected in venous ulcer patients compared with patients who had lymphoedema (p<0.05). Tissue haemosiderin was detected in all ulcer types investigated. No correlation was found between the amounts of haemosiderin deposited in the tissue and the amount found in urine (r(2)=0.06). CONCLUSIONS: Haemosiderin is present in the urine of most patients with venous ulcers but not in ischaemia ulcers.     

Standardised method of surgical treatment of chronic leg ulcers

Healing and recurrence rates were compared in leg ulcers of different aetiology in 385 patients with 406 chronic leg ulcers. Standard treatment was excision of the ulcer followed by meshed split-skin grafting and correction of superficial venous insufficiency in the area. The median age of the patients was 75 years (range 16–95). After one year 345 patients with 357 leg ulcers were alive. Overall healing rate was 64% (227 in 357 legs) after one year. The best results were achieved in traumatic ulcers (31 in 36 ulcers) and worst for the arterial ulcers (4 in 20 ulcers). Recurrence rate in venous and venous/ischaemic ulcers was 14% (33 in 235 legs) and 8% (n=3) in the traumatic ulcers. Vasculitic ulcers tend to recur 59% (n=10), but the graft does relieve pain.     

Excision and meshed skin grafting for leg ulcers resistant to compression therapy

BACKGROUND: The aim of this study was to determine the success of excision and meshed skin grafting for chronic leg ulcers. The effects of different ulcer aetiology and ulcer size on outcome were also assessed. METHODS: All patients who had excision and mesh grafting for chronic leg ulceration between January 1996 and December 2004 at St Thomas' Hospital were reviewed. Recurrence was classified as any breakdown of the ulcer during follow-up. RESULTS: Sixty-two patients with 100 chronic leg ulcers underwent operation. Seventy-two of the ulcers were venous and the median ulcer size was 36 (range 1.5-192) cm2. Only three patients left the hospital with their ulcers unhealed, but ulcers had recurred in 28 (28 per cent) by 2 months. A further 17 ulcers recurred later, with just over half (55 per cent) remaining healed by 5 years. There was no difference between the recurrence rates of venous ulcers and ulcers of other aetiologies (P=0.980), or large (more than 10 cm2) and small ulcers (P=0.686). CONCLUSION: Wide local excision and meshed skin grafting benefitted over half of these patients with refractory leg ulcers. Recurrence was most likely to occur in the first 2 months and, provided that ulcers were healed at this time, there was a low rate of further breakdown.     

Autologous fibroblasts to treat deep and complicated leg ulcers in diabetic patients

Large complicated leg ulcers, not responsive to standard therapy, after surgical debridement and under parenteral specific antibiosis, must be occlusively covered to improve wound healing. In 10 diabetic patients with deep (Wagner degree 3), large, and Staphylococcus aureus (n=7) or Pseudomonas aeruginosa (n=5)-infected leg (n=1), or foot (n=9) ulcers, we have applied, as a coverage, meshes of in vitro expanded autologous fibroblasts. Complete ulcer healing was observed in seven patients after 8, 12, 12, 14, 16, 18, and 20 weeks from the first graft application (Figures 2 and 3). Two patients had >70% wound healing at 20 and 28 weeks after the first treatment. One patient, previously submitted to a bypass vascular procedure, died of acute myocardial infarction 16 weeks after the first fibroblast autograft application and with a healing wound evenly filled with granulation tissue. In our opinion, the application of autologous in vitro expanded fibroblasts is a satisfactory therapeutic option to treat large leg ulcers and is particularly indicated in patients with chronic diseases such as diabetes or autoimmune diseases on steroid treatment.