Basic fibroblast growth factor accelerates and improves second-degree burn wound healing.

Second-degree burns are sometimes a concern for shortening patient suffering time as well as the therapeutic choice. Thus, adult second-degree burn patients (average 57.8 +/- 13.9 years old), mainly with deep dermal burns, were included. Patients receiving topical basic fibroblast growth factor (bFGF) or no bFGF were compared for clinical scar extent, passive scar hardness and elasticity using a Cutometer, direct scar hardness using a durometer, and moisture analysis of the stratum corneum at 1 year after complete wound healing. There was significantly faster wound healing with bFGF, as early as 2.2 +/- 0.9 days from the burn injury, compared with non-bFGF use (12.0 +/- 2.2 vs. 15.0 +/- 2.7 days, p<0.01). Clinical evaluation of Vancouver scale scores showed significant differences between bFGF-treated and non-bFGF-treated scars (p<0.01). Both maximal scar extension and the ratio of scar retraction to maximal scar extension, elasticity, by Cutometer were significantly greater in bFGF-treated scars than non-bFGF-treated scars (0.23 +/- 0.10 vs. 0.14 +/- 0.06 mm, 0.59 +/- 0.20 vs. 0.49 +/- 0.15 mm: scar extension, scar elasticity, bFGF vs. non-bFGF, p<0.01). The durometer reading was significantly lower in bFGF-treated scars than in non-bFGF-treated scars (16.2 +/- 3.8 vs. 29.3 +/- 5.1, p<0.01). Transepidermal water loss, water content, and corneal thickness were significantly less in bFGF-treated than in non-bFGF-treated scars (p<0.01).

Combined surgical excision and radiation therapy for keloid treatment.

Various methods have been attempted for the treatment and management of keloids; however, there is little satisfactory clinical evidence in long-term follow ups. Also, there is a preference for occurrence and recurrence in anatomic location. Usually anatomic locations with higher regional tension and more sebaceous glands are inclined toward pathogenesis. Thirty-eight keloids treated with combined surgical excision and postoperative irradiation, using electron beams with only a 10-mm opening by lead shielding, were investigated at a mean follow up of 4.4 +/- 2.5 years (range, 1-9 years) at a single institute. Ten locations such as the ear (n = 6), neck (n = 3), and upper lip (n = 1) were among the craniofacial locations. The hardness of the keloids and posttreatment scars was clinically and objectively tested with the Vancouver scar scale and a durometer, which is often used for the industrial measurement of thread balls and rubber. At a mean of 4.4 +/- 2.5 years of follow up, the clinical characteristics of the scars were significantly better posttreatment as 2.6 +/- 0.5 versus 1.0 +/- 0.6, 3.7 +/- 0.7 versus 1.7 +/- 0.7, 2.9 +/- 0.4 versus 1.3 +/- 0.5, and 2.7 +/- 0.5 versus 1.3 +/- 0.5 (keloid scars versus posttreatment scars: pigmentation, pliability, height and vascularity, respectively, P < 0.01). The durometer readings were significantly lower posttreatment, 15.2 +/- 3.9 versus 7.7 +/- 2.9 (keloid scars versus posttreatment scars, P < 0.01). The recurrence rate was 21.2% overall with none in craniofacial locations. Therefore, the combined treatment of surgical excision and postoperative electron beam irradiation is effective for scar quality and reducing the recurrence rate in long-term follow up.

Acceleration of sensory neural regeneration and wound healing with human mesenchymal stem cells in immunodeficient rats.

The sensory nerve is highly involved in lower extremity wound healing. In diabetic and vascular diseases, impaired nerve function and blood flow delay wound healing. Tissue regeneration using adult stem cells is a targeted therapeutic modality in disorders of nerve and blood supply. Effective delivery using an autologous vascularized fascial flap as a vehicle of stem cells leads to severed sensory nerve recovery, local tissue blood flow, and wound healing. Human MSCs (hMSCs) were transfected with green fluorescent protein (GFP) cDNA and tested for efficiency and proliferation in vitro. The nude rat model with femoral vessel and saphenous nerve severance and ligation was wrapped with a vascularized epigastric flap for GFP-hMSC, fibroblast growth factor-2 (FGF-2), or a combination of both after 2 weeks. Maximum nerve conduction velocity recovered to 70% of the presurgical level in the GFP-hMSC- and FGF-2-treated group at 2 weeks. Blood flow and nerve conduction velocity were positively correlated at 1 week. Wound healing in the ipsilateral paw had significantly improved by 1 week. Histologically, blood vessels and nerves are very organized, and regenerated neuron immunoreactivity of GAP-43 and a nerve regrowth marker of S-100 were remarkable in the human GFP (hGFP)-hMSC and FGF-2-treated group at 2 weeks; therefore, sensory nerve regeneration, blood flow, and wound healing were improved by the administration of stem cells and FGF-2 via a vascularized flap. This may be implicated in clinical denervated and reduced circulation tissue wound healing.

Attenuation of cysteinyl leukotrienes induces human mesenchymal stem cell differentiation.

Although there are numerous investigations describing bone marrow cells or bone-marrow derived cells at the site of such injuries as bone fractures, infarction and subsequent ischemic reperfusion injury, or cutaneous wounds, little is know about the factors that affect the cells in those clinical situations. Cysteinyl leukotrienes have been extensively investigated in airway diseases that may eventually lead to lung fibrosis; while the engraftment of mesenchymal stem cells have been shown to reverse bleomycin-induced lung fibrosis in vivo. Therefore, we elucidated the involvement of cysteinyl leukotrienes in human mesenchymal stem cell proliferation and differentiation. Human mesenchymal stem cells express the cysteinyl leukotriene type 1 receptor. Various doses of pranlukast, which is a specific cysteinyl leukotriene type 1 receptor antagonist, failed to affect the proliferation of cells; however, 10(-6) M of pranlukast significantly induced cellular cytoplasmic differentiation by showing microvilli sprouting and the emersion of rough endoplasmic reticulum within a 16-hour(s) incubation. Additionally, pranlukast-induced fibronectin protein production by human mesenchymal stem cells. Therefore, attenuation of the cysteinyl leukotriene pathway contributes to human mesenchymal stem cell differentiation and may contribute to modulation of the local injury site.

The quality of pediatric burn scars is improved by early administration of basic fibroblast growth factor.

Pediatric burn wounds can be problematic because an accurate evaluation is difficult as the result of anatomically immature vasculature or immobilization failure, especially in patients with second-degree burns, and because the burn surface areas and the burn depth tend to worsen over the course of time. Delayed wound healing results in unsightly scarring, such as hypertrophic scars, which are problematic both esthetically and functionally. Among cytokines and growth factors, basic fibroblast growth factor (bFGF) is clinically proven, having demonstrated accelerated acute and chronic wound healing. Accelerated wound healing may lead to improved scarring. To elucidate the effects of bFGF on second-degree pediatric burn wounds, a comparative study was performed. A total of 20 pediatric patients ranging from 8 month to 3 years (average 1 year, 3 months +/- 6 months) who suffered from the burns by various causes were divided into two groups, conventional (n = 10) and treatment with bFGF (n = 10). A moisture meter, used to objectively measure the stratum corneum and epithelial-mesenchymal functions, was used to assess scars at least 1 year after wound healing. Clinical evaluation of pigmentation, pliability, height, and vascularity demonstrated significant differences between conventional and bFGF-treated scars (1.7 +/- 0.55 vs 0.7 +/- 0.58, 2.4 +/- 0.82 vs 1.1 +/- 0.69, 1.8 +/- 0.66 vs 0.5 +/- 0.57, 1.9 +/- 0.63 vs 0.8 +/- 0.68; conventional vs bFGF-treated, pigmentation, pliability, height, and vascularity, respectively, P < .01). The effective contact coefficient was significantly greater in conventional wounds than bFGF-treated wounds (14.6 +/- 1.68 % vs 8.7 +/- 2.82 %; conventional vs bFGF, P < .01) and bFGF-treated wounds demonstrated significantly less transepidermal water loss values than conventional treatment (8.3 +/- 1.90 g/m/h vs 5.7 +/- 1.85 g/m/hr; conventional vs bFGF, P < .01). Pediatric burn patients treated with bFGF showed less damaging function of the stratum corneum after healing both in clinical assessment and moisture meter analysis.

A polyurethane dressing is beneficial for split-thickness skin-graft donor wound healing.

Few comparative studies have been performed on the various wound-dressing materials or methods proposed for use. To clarify the efficacy of wound dressing, 35 patients (17 females, aged 44.8+/-26.86 years and 18 males, aged 35.4+/-29.70) were subjected to a prospective study comparing a polyurethane dressing and a hydrogel dressing for split-thickness skin donors from the lateral thighs. We examined their clinical usefulness such as accelerated healing time, frequency of changing the dressing, degree of pain, or amount of exudates, and performed moisture meter analysis at 1 month and 1 year after re-epithelialization, which reflects the quality of the stratum corneum and subsequent scarring. The polyurethane dressing was superior to hydrogel in the wound healing time, amount of exudates, and frequency of dressing changes: the hydrogel was better for regulating the degree of pain. There was a positive correlation between transepidermal water loss and the effective contact coefficient, which indicates skin barrier function and affected by skin surface electrolytes and reflects water content, in moisture meter analysis (r(2)=0.32, p<0.01). Transepidermal water loss returned to the control level at 1 year after healing with both dressings. The effective contact coefficient of the polyurethane wound was significantly lower than that of hydrogel at 1 month (p<0.01), while both dressing wounds demonstrated significantly higher values at both 1 month and 1 year compared to the control (p<0.01). The polyurethane dressing is therefore superior both clinically and in moisture meter analysis.

Elevated circulating leukemia inhibitory factor in patients with extensive burns.

To investigate circulating cytokine responsiveness in major burns in association with the systemic stress response system, we tested hypothalamic-pituitary-adrenal (HPA) axis markers in extensive burn cases treated in the Department of Plastic and Reconstructive Surgery at Nagasaki University. The HPA axis is a major stress response system, and the leukemia inhibitory factor (LIF) may be a potent mediator of the HPA axis; therefore, circulating LIF levels in burn patients were studied. Twenty extensively burned patients (burn surface area, >20%), ie, 10 women and 10 men, 37 to 77 years of age (average: 59.1 +/- 12.10 years), were assessed. Circulating LIF, adrenocorticotropic hormone (ACTH), other inflammatory markers, and 24-hour urinary free cortisol excretion levels were investigated. LIF levels were greater in patients who died than in those who survived (186.1 +/- 80.41, 83.5 +/- 64.49 pg/ml, respectively, P < .001) at 36 hours after injury. ACTH levels were more significantly elevated in fatal cases than in those who survived. (41.3 +/- 8.28, 25.2 +/- 7.84 pg/ml, respectively, P < .0001). Twenty-four hour (24 to 48 hours after injury) pooled urinary free cortisol excretion levels also were significantly greater in fatal cases than in the surviving patient group (235.0 +/- 36.49 microg/day, 69.0 +/- 18.04 microg/day, respectively, P < .0001). The correlation between serum LIF and urine free cortisol was significant (r = .30; P < .01) as was the correlation of serum LIF with plasma ACTH (r = .24; P < .01). Serum LIF as well as HPA axis activity markers is a good marker of disease severity and prognosis in patients with extensive burns.

A basic fibroblast growth factor improved the quality of skin grafting in burn patients.

To avoid hypertrophic scars in burn wounds, the simultaneous application of basic fibroblast growth factor (bFGF) with regular surgical debridement and skin grafting was investigated for skin hardness by clinical examination and instrumental measurement. As little is known about the role of bFGF in wounds, burn wound scars were tested for hardness. Burn scars in various anatomical locations at least 1 year after final wound healing clinically demonstrated a significantly lower hard score in bFGF-treated wounds than in non-bFGF wounds (0.95+/-0.51 versus 2.3+/-0.66, respectively, p<0.01). In addition, a durometer, which is widely used in industry to measure materials similar to skin, such as rubber and thread-balls, demonstrated a significantly lower reading in bFGF-treated wounds than in non-bFGF wounds (7.9+/-3.64 versus 15.5+/-4.39, bFGF versus non-bFGF, respectively, p<0.01). The results demonstrated that burn wounds treated with clinically approved bFGF might contribute to a better cutaneous wound quality, at least in terms of hardness.