Effectiveness of autologous preparation rich in growth factors for the treatment of chronic cutaneous ulcers. Clinical efficacy of basic fibroblast growth factor (bFGF) for diabetic ulcer. Recombinant human granulocyte-macrophage colony-stimulating factor hydrogel promotes healing of deep partial thickness burn wounds. A multicenter clinical trial of recombinant human GM-CSF hydrogel for the treatment of deep second-degree burns. A short course of granulocyte-colony-stimulating factor to accelerate wound repair in patients undergoing surgery for sacrococcygeal pilonidal cyst: proof of concept. Effect of recombinant adeno-associated virus vector-mediated vascular endothelial growth factor gene transfer on wound healing after burn injury* [Clinical observation of basic fibroblast growth factor combined with topical oxygen therapy in enhancing burn wound healing]. Randomized, multicenter, double-blind, and placebo-controlled trial using topical recombinant human acidic fibroblast growth factor for deep partial-thickness burns and skin graft donor site. [Clinical observation of the long-term effects of rhEGF on deep partial-thickness burn wounds]. Randomized trial of topically applied repifermin (recombinant human keratinocyte growth factor-2) to accelerate wound healing in venous ulcers. [Clinical study on repair of burn wounds of degree II with recombinant human epidermal growth factor in elderly patients]. Enhancement of wound healing by topical treatment with epidermal growth factor. The efficacy and safety of epidermal growth factor in treatment of diabetic foot ulcers: the preliminary results. Effectiveness of recombinant human platelet-derived growth factor for the treatment of diabetic neuropathic foot ulcers. Long-term outcome study of growth factor-treated pressure ulcers. Topical Treatment of Pressure Ulcers with Nerve Growth Factor Randomised placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor for second-degree burns A local application of recombinant human fibroblast growth factor 2 for tibial shaft fractures: A randomized, placebo-controlled trial. What is the prevalence of hypertrophic scarring following burns? [Effect of recombinant human granulocyte-macrophage colony-stimulating factor on wound debridement and healing of deep II thickness burn]. [Effect of recombinant human granulocyte-macrophage colony stimulating factor on wound healing in patients with deep partial thickness burn]. 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.
Autologous Preparation Rich in Growth Factors ( PRGF ) , a small volume of plasma enriched in platelets , is a novel therapeutic strategy for the acceleration of the wound healing of a wide range of tissues because of the continuous release of multiple growth factors , including PDGF-AB , TGF-beta1 , IGF-I , HGF , VEGF-A , and EGF . In this article , we have characterized the PRGF preparation and design ed a r and omized open-label controlled pilot trial to evaluate the effectiveness of PRGF in the treatment of chronic cutaneous ulcers . Results showed that at 8 weeks , the mean percentage of surface healed in the  PRGF  group was 72.94 % + /- 22.25 % whereas it was 21.48 % + /- 33.56 % in the control group ( p < 0.05 ) . These results , with the limitations of a pilot study , suggest that topical application of PRGF is more effective than st and ard therapy in helping a chronic ulcer to heal Basic fibroblast growth factor ( bFGF ) has been shown to promote wound healing . The present trial evaluated the clinical efficacy of bFGF for diabetic ulcer , a type of refractory skin ulcer , and the dose-response relationship . This was design ed as a r and omized , double-blind , dose-ranging , placebo-controlled trial . A total of 150 patients with non-ischaemic diabetic ulcers measuring 900 mm2 or less were r and omized into a placebo group ( n = 51 ) , a 0.001 % bFGF group ( n = 49 ) and a 0.01 % bFGF group ( n = 50 ) , and 148 of these patients received treatment for 8 weeks or less . The efficacy evaluation was carried out on 139 patients who met the protocol in this trial . The primary outcome was the percentage of patients showing 75 % or greater reductions in the area of ulcer . The area of ulcer decreased by 75 % or more in 57.5 % ( 27/47 ) , 72.3 % ( 34/47 ) , and 82.2 % ( 37/45 ) in the placebo , 0.001 % bFGF and 0.01 % bFGF groups , respectively , and differences were significant between the 0.01 % bFGF and placebo groups ( p = 0.025 ) . The cure rate was 46.8 % ( 22/47 ) , 57.4 % ( 27/47 ) , and 66.7 % ( 30/45 ) in the placebo , 0.001 % bFGF and 0.01 % bFGF groups , respectively . The findings obtained in this trial showed wound healing accelerating effects of bFGF on diabetic ulcers OBJECTIVE To assess the effects of recombinant human granulocyte/macrophage colony-stimulating factor ( rhGM-CSF ) hydrogel on the healing of deep partial thickness burn wounds . METHODS Ninety three wounds of 65 burn patients who suffered from a deep partial thickness burn of < 5 % TBSA and could not heal over 3 weeks were included in this study . The patients were r and omly assigned to use rhGM-CSF hydrogel ( GC group , n=32 ) or hydrogel without rhGM-CSF ( control group , n=33 ) . rhGM-CSF hydrogel or hydrogel without rhGM-CSF was topically applied to the wounds , the dressing was changed once a day . Wound healing time and percentage , wound discharge , periwound inflammation , the positive wound swabs culture count , and adverse drug reactions were observed and compared between two groups . RESULTS Healing time was 12.2 ± 5.0 days after the application of rhGM-CSF hydrogel . This was significantly shorter than that of control wounds ( 15.5 ± 4.7 days ) . Healing percentage at 14 days in the rhGM-CSF-treated wounds was 97.5 ± 7.7 % , which was markedly higher than the control ( 85.9 ± 6.8 % ) . At 3 , 6 , 12 , 14 day , the GC group was significantly superior to the control group with respect to the score of periwound inflammation , wound purulence and discharge . The positive wound swabs culture count of the GC group on the 7th and 14th day post-treatment was 14 and 4 , respectively , which was significantly lower than the control . CONCLUSION rhGM-CSF hydrogel promotes the healing process of deep partial thickness burns effectively . No adverse reaction of the drug was observed during the study Wound healing is a complex and dynamic biological process . The efficacy and safety of a recombinant human granulocyte-macrophage colony-stimulating factor ( rhGM-CSF ) hydrogel to promote deep-second-degree burn wound healing is evaluated in this study . In this multicenter , r and omized , double-blind , and placebo-controlled clinical trial , 90 patients with deep second-degree burns were r and omly assigned into two groups . Complete healing time and percentage of wound healing at different time points were observed and side effects were recorded . A statistically significant difference was noted at each time point ( p<0.01 ) . No side effects were observed . These results suggest that rhGM-CSF hydrogel can significantly accelerate deep second-degree burn wound healing and is considered to be safe BACKGROUND AIMS Stem cells , namely easily accessible bone marrow-derived cells ( BMC ) , are reportedly capable of tissue repair in different damaged organs and might favor wound healing . The present study was undertaken to evaluate the feasibility and safety of BMC mobilization induced by granulocyte-colony-stimulating factor ( G-CSF ) in patients undergoing surgery for sacrococcygeal pilonidal cysts ( SPC ) . To evaluate the possible clinical benefit of G-CSF in reducing the time to complete resolution , a comparison with a control group receiving surgery without G-CSF was performed . METHODS Eight patients with complex SPC were included in this prospect i ve trial . Patients were treated with G-CSF ( 5 µg/kg b.i.d . ) for 3 consecutive days ; st and ard surgical exeresis of the pilonidal cyst was scheduled on day 2 of mobilization . Mobilization was assessed in terms of circulating CD34(+ ) cells and granulocyte-macrophage colony-forming unit ( CFU-GM ) progenitors . RESULTS Mobilization of CD34(+ ) cells and CFU-GM occurred in all patients , along with a marked increase in white blood cells ( median peak value 28 435/µL , day 3 ) . G-CSF was well tolerated and no adverse events occurred . All patients received the planned surgical treatment without any complications . Interestingly , the G-CSF group patients had a median time to resolution ( 117 days , range 110 - 130 ) significantly shorter than control patients ( 145 days , range 118 - 168 ) ( P = 0.034 ) . CONCLUSIONS G-CSF administration , along with BMC mobilization , is feasible and well tolerated in patients undergoing surgery for SPC ; clinical results compare favorably with those observed in controls not receiving G-CSF ; the results suggest the potential use of G-CSF as an additional treatment to accelerate wound healing in patients undergoing surgery Objective The purpose of this study was to investigate the effect of recombinant adeno-associated viral ( rAAV ) vector-mediated human vascular endothelial growth factor ( VEGF165 ) transfer on experimental burn wounds . Design R and omized experiment . Setting Research laboratory . SubjectsC57BL/6 male mice weighing 25–30 g. Interventions Mice were immersed in 80 ° C water for 10 secs to achieve a partial-thickness scald burn . Animals were r and omized to receive at two injection sites on the edge of the burn either 1011 copies of the rAAV-VEGF165 or the vector carrying the control and inert gene & bgr;-galactosidase ( rAAV-LacZ ) . On day 14 the animals were killed . Burn areas were used for histologic examination , evaluation of VEGF expression ( immunohistochemistry ) and VEGF wound content ( enzyme-linked immunosorbent assay ) , determination of wound nitrite , and measurement of messenger RNA ( mRNA ) for endothelial and inducible nitric oxide synthase ( eNOS and iNOS ) . Measurements and Main Results rAAV-VEGF165 increased epithelial proliferation , angiogenesis , and maturation of the extracellular matrix . Furthermore , gene transfer enhanced VEGF expression , studied by immunohistochemistry , and the wound content of the mature protein ( rAAV-LacZ , 11 ± 5 pg/wound ; rAAV-VEGF165 , 104 ± 7 pg/wound ) . Moreover , VEGF165 gene transfer increased wound content of nitrate . Finally , rAAV-VEGF165 administration enhanced the messenger RNA for eNOS ( rAAV-VEGF165 , 1.1 ± 0.2 relative amount of eNOS mRNA ; rAAV-LacZ , 0.66 ± 0.3 relative amount of eNOS mRNA ) and iNOS ( rAAV-VEGF165 , 0.8 ± 0.09 relative amount of iNOS mRNA ; rAAV-LacZ , 0.45 ± 0.05 relative amount of iNOS mRNA ) . Conclusion Our study suggests that rAAV-VEGF gene transfer may be an effective therapeutic approach to improve clinical outcomes after thermal injury OBJECTIVE To investigate the efficacy of basic fibroblast growth factor ( bFGF ) combined with topical oxygen therapy for  deep II degree burn wounds  , by comparing the effects of bFGF combined with topical oxygen therapy and bFGF with routine therapy . METHODS From February 2004 to July 2009 , 85 patients with deep II degree burn wounds ( 117 wounds ) were enrolled and divided into 4 groups r and omly according to different treatments . There was no significant difference in sex , age , disease course , wound size , and wound treatment size among 4 groups ( P > 0.05 ) . In group A , 18 patients ( 28 wounds ) were treated routinely ; in group B , 23 patients ( 30 wounds ) were treated with routine methods and topical oxygen therapy ; in group C , 19 patients ( 25 wounds ) were treated with routine methods and bFGF therapy ; and in group D , 25 patients ( 34 wounds ) were treated with routine methods and bFGF/topical oxygen therapy . Topical oxygen therapy was administered to the wound for 90 minutes per day for 3 weeks . The bFGF therapy was applied everyday ( 150 U/cm2 ) for 3 weeks . RESULTS All cases were followed up 6 - 12 months ( 9 months on average ) . The wound healing times in groups A , B , C , and D were ( 27.3 + /- 6.6 ) , ( 24.2 + /- 5.8 ) , ( 22.2 + /- 6.8 ) , and ( 18.2 + /- 4.8 ) days , respectively ; showing significant difference between group A and group D ( P < 0.05 ) . The wound healing rates in groups A , B , C , and D were 67.8 % + /- 12.1 % , 85.1 % + /- 7.5 % , 89.2 % + /- 8.3 % , and 96.1 % + /- 5.6 % , respectively ; showing significant differences between group A and groups B , C , D ( P < 0.05 ) . The therapic effective rates in groups A , B , C , and D were 75 % , 90 % , 92 % , and 100 % , respectively ; showing significant difference between group A and group D ( P < 0.05 ) . The Vancouver scar scale scoring of group D 6 months after treatment was better than that of group A ( P < 0.05 ) . CONCLUSION The bFGF combined with topical oxygen therapy can enhance deep II degree burn wound healing . Furthermore , the therapy method is simple and convenient Wound healing is a dynamic and complex biologic process that could be accelerated by growth factors . To investigate the efficacy of topical recombinant human acidic fibroblast growth factor ( rh-aFGF ) treatment in deep partial-thickness burn or skin graft donor sites , we design ed a r and omized , multicenter , double-blind , and placebo-controlled clinical trial . The healing rate , fully healed rate , and healing time were evaluated to assess the efficacy of rh-aFGF application . Laboratory examinations and abnormal signs were used to assess the side and toxic effects . The results showed that the healing rate of burn wounds and skin graft donor sites treated by rh-aFGF was significantly higher than that by placebo , and the mean healed time of burn wounds and skin graft donor sites in the rh-aFGF group was significantly the shorter than that in the placebo group . In conclusion , topical administration of rh-aFGF can accelerate the wound healing process and shorten the healed time . It is a potential therapeutic application for promoting healing of deep partial-thickness burns or skin graft donor sites OBJECTIVE To evaluate the safety and long-term effect of recombinant human epithelial growth factor ( rhEGF ) on deep partial-thickness burn wounds . METHODS Thirty-seven burn patients were enrolled in this study and were observed by r and omized , double-blinded and placebo-controlled protocol . An area of deep partial-thickness burn wounds from each patient was divided into control ( C ) and treatment ( T ) portions . The wound in C was treated with normal saline while that in T with rhEGF . The patients were followed-up for 1 and 4 years after wound healing . The healed wounds were evaluated by modified Vancouver scar scale in terms of scar index ( SI ) . RESULTS 1 year after wound healing , it was found that the SI in T group ( 7.19 + /- 1.67 ) was obviously lower than that in C group ( 8.92 + /- 1.78 , P < 0.01 ) . The SI in T group ( 6.12 + /- 1.54 ) was still evidently lower than that in C group ( 8.09 + /- 1.81 , P < 0.01 ) four years after wound healing . There were no signs of development of tumor or cancer in all the tested burn wound areas . CONCLUSION External application of rhEGF might be beneficial to the healing quality of deep partial-thickness burn wound with less scar formation and better long-term effects , and it is safe About 600,000 people in the United States are estimated to be affected by venous ulcers . The cornerstone of care of chronic venous ulcers involves the application of compression b and ages . Other therapies include treatment of associated infection , treatment for edema and inflammation , and debridement when necessary . Repifermin , a recombinant human KGF-2 ( fibroblast growth factor-10 ) , exerts a proliferative effect on epithelial cells , in vitro and in vivo , and has been shown to accelerate wound healing in several experimental animal models . A r and omized , double-blind , parallel-group , placebo-controlled , multicenter study was conducted to evaluate the safety and efficacy of topical repifermin treatment , for 12 weeks , in the healing of chronic venous ulcers in 94 patients .  Repifermin was shown to accelerate wound healing , with significantly more patients achieving 75 % wound closure with repifermin than with placebo . The treatment effect appeared more marked for a subgroup of patients with initial wound areas < or = 15 cm2 and wound ages of < or = 18 months . A longer duration of treatment ( e.g. , 26 weeks ) may allow better differentiation of the benefit of repifermin compared with placebo , particularly with respect to complete wound closure . The safety assessment showed that repifermin was well tolerated OBJECTIVE To explore the therapeutic effect of recombinant human epidermal growth factor ( rhEGF ) for burn wounds of degree II in the elderly patients . METHODS From February 2003 to October 2008 , 80 patients with burn wounds of degree II were treated and r and omly divided into two groups ( n=40 ) . In treatment group , there were 24 males and 16 females with an average age of 70 years ( 60 - 86 years ) , including 20 cases of superficial II degree and 20 cases of deep II degree . Burn wounds were caused by flame in 23 cases , by hot liquid in 16 cases , and by electricity in 1 case . The mean time from injury to hospitalization was ( 2.87 + /- 2.57 ) hours . The wounds were treated with silver sulfadiazine ( SD-Ag ) and rhEGF . In control group , there were 18 males and 22 females with an average age of 69 years ( 61 - 83 years ) , including 19 cases of superficial II degree and 21 cases of deep II degree . Burn wounds were caused by flame in 23 cases , by hot liquid in 14 cases , by electricity in 2 cases , and by chemistry in 1 case . The mean time from injury to hospitalization was ( 3.39 + /- 3.33 ) hours . The wounds were treated with SD-Ag . The dressing was changed every day until wounds healing . There were no significant differences in general data between two groups ( P > 0.05 ) . RESULTS Wound did not heal in 1 case ( deep II degree ) of treatment group and in 5 cases ( deep II degree ) of control group over 40 days and free skin graft was used to repair wound . One case ( superficial II degree ) in control group gave up treatment . One case ( deep II degree ) died of pulmonary infection in treatment group . These cases were excluded and 72 cases were analysed . No other side reactions were observed in treatment group except for flash stabbing pain ( 4 cases ) and pruritus ( 2 cases ) . Wound infection occurred in 5 cases of the control group and in 3 cases of the treatment group , and wound healed after symptomatic treatment . The healing time of burn wound was ( 14.30 + /- 1.26 ) days ( superficial II degree ) and ( 26.11 + /- 2.97 ) days ( deep II degree ) in the treatment group , was ( 16.22 + /- 1.40 ) days ( superficial II degree ) and ( 29.13 + /- 4.99 ) days ( deep II degree ) in control group , showing significant difference between two groups ( P < 0.05 ) . CONCLUSION In combined treatment , rhEGF can promote the healing of burn wounds of degree II in the elderly patients Experimental studies in animals have demonstrated that the topical application of epidermal growth factor accelerates the rate of epidermal regeneration of partial-thickness wounds and second-degree burns . We conducted a prospect i ve , r and omized , double-blind clinical trial using skin-graft-donor sites to determine whether epidermal growth factor would accelerate the rate of epidermal regeneration in humans . Paired donor sites were created in 12 patients who required skin grafting for either burns or reconstructive surgery . One donor site from each patient was treated topically with silver sulfadiazine cream , and one was treated with silver sulfadiazine cream containing epidermal growth factor ( 10 micrograms per milliliter ) . The donor sites were photographed daily , and healing was measured with the use of planimetric analysis . The donor sites treated with silver sulfadiazine containing epidermal growth factor had an accelerated rate of epidermal regeneration in all 12 patients as compared with that in the paired donor sites treated with silver sulfadiazine alone . Treatment with epidermal growth factor significantly decreased the average length of time to 25 percent and 50 percent healing by approximately one day and that to 75 percent and 100 percent healing by approximately 1.5 days ( P less than 0.02 ) . Histologic evaluation of punch-biopsy specimens taken from the centers of donor sites three days after the onset of healing supported these results . We conclude that epidermal growth factor accelerates the rate of healing of partial-thickness skin wounds . Further studies are required to determine the clinical importance of this finding OBJECTIVE To evaluate the efficacy and safety of recombinant human epidermal growth factor ( rh-EGF ) in healing foot ulcers in diabetic patients . METHODS A total of 28 subjects with foot ulcers were recruited into the pilot study . Patients who had obvious peripheral arterial disease , trans-tibial amputation , plastic surgery or skin flap , and skin graft were excluded . The properly debrided wounds and the non closure wounds after toe amputation were included . When the wounds became clean or uninfected , they received twice-a-day treatment with 0.005 % Easyef and hydrocolloid dressing . The size and severity of the wounds were evaluated . Others such as blood sugar , renal and hepatic function , serum albumin , vascular condition , foot infection or osteomyelitis were assessed . RESULTS All of 28 patients had positive response of granulation ( 100 % ) . Complete healing was noted in 13 out of 23 subjects and finished 8-week follow-up ( 56.5 % ) . The rates of wound closure were 43.3 % , 59.9 % , 68.7 % , and 84.8 % in week 2 , 4 , 6 and 8 , respectively , regardless of the severity . Being dropped out , three patients needed further interventions . No skin allergic reaction . Over-granulation was observed in one female patient ( 3.7 % ) , but as minor . CONCLUSIONS Easyef has positive effects on healing of moderate-to-severe foot ulcers and demonstrated being safe to diabetic patients . The drug had high tolerability and compliance The goal of this study was to estimate the effectiveness in actual clinical practice of recombinant human platelet-derived growth factor ( rhPDGF ) for the treatment of diabetic neuropathic foot ulcer ( DNFU ) . Previously published pivotal trials have shown that by the 20th week of care 35 percent more ulcers healed in the group r and omized to receive rhPDGF than those who did not receive rhPDGF ( i.e. , a relative risk [ RR ] of about 1.35 ) . This represents an estimate of the efficacy of rhPDGF under the tightly controlled conditions of r and omized clinical trials . Treatment effectiveness under st and ard clinical practice was estimated in a retrospective cohort study , controlling for treatment selection bias using propensity scores . We noted 24,898 individuals with a DNFU , of whom 9.6 percent received rhPDGF .  We successfully created a propensity score model that evenly balanced many wound characteristics between those who received rhPDGF and those who did not . We created five groups , which varied from those least likely to receive rhPDGF to those most likely to receive rhPDGF . The RR , controlling for the propensity , to receive rhPDGF for a healed wound after treatment with rhPDGF as compared with st and ard care was 1.32 ( 1.22 , 1.38 ) . With respect to amputation , the RR for undergoing amputation after receiving rhPDGF was 0.65 ( 0.54 , 0.78 ) as compared with those who did not receive rhPDGF . Within the limitations of our study , rhPDGF is more effective than st and ard therapy in both helping a wound to heal and preventing amputation , and its effect is similar to the efficacy estimates from previously published r and omized controlled trials BACKGROUND Exogenous application of growth factors have been reported in an attempt to accelerate healing of chronic wounds .  Most of the trials were of brief duration with short to no follow-up periods . Long-term outcome studies are sparse for pressure ulcer therapies with success rates around 30 % for both operative and nonoperative treatments . METHODS Follow-up evaluations were performed serially up to 12 months for patients completing a 35 day blinded , placebo-controlled cytokine clinical trial of pressure ulcers . RESULTS Fifty-four of 61 patients completed the follow-up period with 68.5 % of the patients ( 37 of 54 ) being healed after 1 year . Of patients healing > or = 85 % during the active treatment phase , 84.6 % were healed after 1 year compared with 61 % of those that healed < 85 % during treatment ( P < 0.05 ) . CONCLUSION Long-term outcome was better in this growth factor trial than with surgical or st and ard nonoperative treatment of pressure ulcers . Since only patients receiving exogenously applied cytokines achieved > 85 % closure during the treatment phase of the trial , the excellent long-term outcome appears attributable to the cytokine therapy Context  Pressure ulcers of the foot are common in older , debilitated patients . They often cause major morbidity and respond poorly to conventional therapy . Contribution In a 6-week r and omized , double-blind , placebo-controlled study , daily topical application of a solution of nerve growth factor produced statistically significant acceleration in ulcer healing compared with st and ard therapy . Caution s Although application of nerve growth factor appears to be potentially useful in the treatment of pressure ulcers , this study excluded patients with chronic ulceration , diabetes , and peripheral vascular disease . The Editors Pressure ulcers are one of the major causes of morbidity in older people and the most important care problem in nursing home residents ( 1 , 2 ) ; they dramatically increase the cost of medical and nursing care ( 3 ) . In particular , pressure ulcers of the foot are very common and are difficult to heal among elderly immobilized patients .  Pressure ulcers at the malleolus , heel , or both develop as a result of pressure , shear , or friction concentrated on a small area over a bone prominence that lacks subcutaneous tissue . Regardless of stage , prompt treatment is essential . An untreated pressure sore may worsen and lead to cellulitis , chronic infection , or osteomyelitis . Management options for pressure ulcers include local wound care ; surgical repair ; and , more recently , topical application of growth factors . Nerve growth factor is a polypeptide that is involved in a variety of biological activities in several mammalians cells , both in vitro and in vivo ( 4 ) . It is the first and best-characterized member of a family of neurotrophic factors and was originally noted for its part in developing peripheral sensory and sympathetic neurons ( 4 ) . Subsequent studies showed that this molecule is also critically involved in neurite outgrowth , cell survival , and functional activity of forebrain cholinergic neurons and plays a crucial role in aging and memory processes ( 5 , 6 ) . Nerve growth factor can promote the regeneration of injured cells that express nerve growth factor receptors , in both the peripheral and central nervous systems ( 5 ) . There are also strong indications that  nerve growth factor plays an important role in wound healing . Li and colleagues ( 7 ) reported the first evidence supporting this hypothesis : the observation that removal of the submaxillary gl and s , tissue storing large amounts of nerve growth factor , substantially affects recovery of wound healing in mouse skin . Other studies showed that fibroblasts and epithelial cells are able to produce nerve growth factor and are receptive to its specific action ( 5 , 8) . These and other findings support the hypothesis that nerve growth factor , by stimulating growth and differentiation of epithelial-derived cells , might be clinical ly useful in wound healing after skin damage . This hypothesis was strengthened by recent observational studies showing that topical application of nerve growth factor speeded recovery from skin ulcer in humans ( 9 , 10 ) and induced prompt healing and restoration of corneal sensitivity in patients with corneal neurotrophic ulcers ( 11 ) . We evaluated the efficacy of topical application of nerve growth factor compared with conventional topical treatment in patients with severe noninfected pressure ulcers of the foot . Methods Study Sample We performed a r and omized , double-blind , placebo-controlled trial with 6-week follow-up . We screened all patients admitted to the teaching nursing home of Catholic University of the Sacred Heart , Fontecchio , Italy , between 1 September 2000 and 30 May 2002 for enrollment in the study . Patients were eligible if they had a pressure ulcer of the foot that ranged from 1 cm2 to 30 cm2 in total area ( n = 70 ) . We excluded 6 patients who had developed the lesion more than 1 month before admission , 6 patients with terminal illnesses , 10 patients with diabetes , and 5 patients with peripheral vascular diseases . Five patients declined to participate . Therefore , 54 % of the initial patients ( n = 38 ) were considered eligible for and were enrolled in the study . Subsequently , 1 patient in the treatment group died and 1 patient in the control group was lost to follow-up because of admission to the hospital for myocardial infa rct ion . As a result , the final analysis sample consisted of 18 patients in the treatment group and 18 patients in the control group ( Figure 1 ) . Figure 1 . Trial profile . The steering committee of the Catholic University of the Sacred Heart and the institutional review board at the clinical center approved and monitored the study . All patients provided written informed consent at enrollment for prer and omization activities and at the initiation of treatment for follow-up activities and treatment . If patients were cognitively impaired , informed consent was obtained from their families . Study Design and Treatment Protocol s Baseline assessment s were done before r and omization during the first 2 weeks after nursing home admission . Patients were evaluated by using the Minimum Data Set instrument for nursing homes ( 12 , 13 ) in its vali date d translation ( 14 ) . The Minimum Data Set is a comprehensive assessment instrument whose application is now federally m and ated in U.S. nursing homes . The Minimum Data Set form includes information such as demographic characteristics , functional and cognitive status , and nursing needs relevant to care planning . Two summary scales based on Minimum Data Set items have also been design ed to describe patients ' performance in terms of personal activities of daily living ( 15 ) and level of cognitive function ( Cognitive Performance Scale ) ( 16 ) . The assessment also included a complete list of diagnoses and medications . The following indicators of nutritional status were also measured at admission : body mass index , serum albumin level , serum hemoglobin level , serum lymphocyte count , and serum glucose level . To exclude peripheral vascular diseases ( arterial and venous disorders ) and other causes of foot ulceration , arterial and venous color Doppler ultrasonography of the legs was performed in all patients before r and omization . Peripheral arterial disorders were defined as the presence of atherosclerotic plaque leading to stenosis of any grade in 1 or more arterial segments along the iliacfemoralpopliteal axis ; venous disorders included venous thrombosis and varicose veins . Ulcer size and stage were recorded at baseline and every subsequent week for 6 weeks . Outcome measures were collected by a research assistant who was not involved in the study protocol and was completely blinded to patient assignments . To provide highly accurate and precise measures of ulcers , the wound perimeter was traced onto sterile , transparent block paper and the blocks were counted ( 17 ) . Ulcer stage was determined by using the YarkonyKirk scale ( 18 ) . This classification , which uses a 6- grade scaling system , takes ulcer depth ( involvement of dermis , subcutaneous fat , exposed muscle , exposed bone ) into particular consideration . In a previous study , this scale appeared to have good reliability and to guarantee a more thorough assessment of pressure ulcers than other scales ( 18 ) . In addition , digital photographs were taken at baseline and every week during the follow-up period . In all patients , ulcers had been present for at least 1 week before the start of the study and were characterized by a very slow response to local treatment and limited tendency to heal . After the baseline assessment , patients were r and omly stratified by age group , sex , and ulcer surface area according to a computer-generated list . Eighteen patients received nerve growth factor treatment , and 18 received only conventional topical treatment .  A research assistant at the Institute of Neurobiology of the National Research Council , Rome , prepared and labeled the nerve growth factor and placebo solutions . The nursing home staff who administered pressure ulcer medication were blinded to treatment assignment . For both groups , treatment began in the absence of clinical signs and symptoms of active topical infection and after 2 wound cultures performed at different parts of the ulcer showed no bacterial growth . The same preventive skin regimen ( a turning and repositioning program and a pressure-relieving mattress ) was initiated in all patients before r and omization . Thereafter , all patients received the same daily local care : irrigation with normal saline , use of debriding enzymes , and application of opaque hydrocolloid occlusive barriers . Treatment was continued until the wound healed completely or for a maximum of 6 weeks . It is important to emphasize that this treatment duration was comparable to that in previous r and omized , controlled trials assessing the effect of specific treatments for pressure ulcers ( 19 - 21 ) . Treatment Group We used 2.5S murine nerve growth factor , which was purified from submaxillary gl and s according to the method of Bocchini and Angeletti ( 22 ) as modified by Mobley and colleagues ( 23 ) . This murine nerve growth factor is closely homologous to human nerve growth factor ( 24 ) . One milligram of nerve growth factor was dissolved in 20 mL of balanced salt solution , with a final concentration of 50 g/mL. The nerve growth factor solution was dropped daily on the lesion and allowed to dry for 2 to 3 minutes . Control Group A balanced salt solution was used as a placebo and was dropped on the lesion in a manner identical to the nerve growth factor solution . The control preparation was indistinguishable from the growth factor preparation in presentation , color , density , and odor . Except for the topical application of nerve growth factor solution , the same local care procedures were used to treat the ulcers in the control group . Statistical Analysis Quantitative variables are presented as mean values ( SD ) . Differences in baseline characteristics between patients in the control and treatment groups were analyzed in several ways . Quantitative outcomes BACKGROUND Wound healing is a dynamic process that could be accelerated by growth factors . We investigated the effect of recombinant bovine basic fibroblast growth factor ( rbFGF ) on burn healing in a r and omised placebo-controlled trial . METHODS We recruited 600 patients with superficial or deep second-degree burns . Patients received 150 AU/cm2 daily topical rbFGF ( n=300 ) or placebo ( n=300 ) plus vehicle . We assessed healing by photography , punch-biopsy , and clinical examination . FINDINGS All patients treated with rbFGF had faster granulation tissue formation and epidermal regeneration than those in the placebo group . Superficial and deep second-degree burns treated with rbFGF  healed in a mean of 9.9 ( SD 2.5 ) days and 17.0 ( 4.6 ) days , respectively , compared with 12.4 ( 2.7 ) and 21.2 ( 4.9 ) days ( p=0.0008 and p=0.0003 , respectively ) . No adverse effects were seen locally or systemically with rbFGF . INTERPRETATION rbFGF effectively decreased healing time and improved healing quality . Clinical benefits would be shorter hospital stays and the patient 's skin quickly becoming available for harvesting and grafting Fibroblast growth factor 2 ( FGF-2 ) is a potent mitogen for mesenchymal cells , and a local application of recombinant human FGF-2 ( rhFGF-2 ) in a gelatin hydrogel has been reported to accelerate bone union in our animal studies and preparatory dose-escalation trial on patients with surgical osteotomy . We have performed a r and omized , double-blind , placebo-controlled trial in which patients with fresh tibial shaft fractures of transverse or short oblique type were r and omly assigned to three groups receiving a single injection of the gelatin hydrogel containing either placebo or 0.8 mg ( low-dosage group ) or 2.4 mg ( high-dosage group ) of rhFGF-2 into the fracture gap at the end of an intramedullary nailing surgery . Of 194 consecutive patients over 2 years , 85 met the eligibility criteria , and 70 ( 24 in the placebo group and 23 each in low- and high-dosage groups ) completed the 24-week study . The cumulative percentages of patients with radiographic bone union were higher in the rhFGF-2-treated groups ( p = .031 and .009 in low- and high-dosage group , respectively ) compared with the placebo group , although there was no significant difference between low- and high-dosage groups ( p = .776 ) . At 24 weeks , 4 , 1 , and 0 patients in the placebo , low-dosage , and high-dosage groups , respectively , continued to show delayed union . No patient underwent a secondary intervention , and the time to full weight bearing without pain was not significantly different among the three groups ( p = .567 ) . There also was no significant difference in the profiles of adverse events among the groups . In conclusion , a local application of the rhFGF-2 hydrogel  accelerated healing of tibial shaft fractures with a safety profile Hypertrophic scarring  after burns remains a major problem and is considered to be " common " . Pressure garments are commonly used as treatment even though there is little sound data that they reduce the prevalence or magnitude of the scarring . In 1999 we began a study of the efficacy of pressure garments on forearm burns .  After study ing 30 patients , mainly white adults , we found no hypertrophic scar in either those treated with pressure or without . This prompted us to review the literature on the prevalence of hypertrophic scarring after burns and found only four articles with a relatively small number of patients and only three geographical locations . It became clear that the prevalence of hypertrophic scarring is really unknown . We then did a retrospective study of 110 burn survivors and counted all hypertrophic scars of all sizes and locations in all races and found the prevalence hypertrophic scarring to be 67 % which conflicts with the published reports and our prospect i ve study and suggests that further research is necessary . We concluded that a worldwide , prospect i ve survey is necessary to establish the prevalence of hypertrophic scarring after burns . In this article we are calling for and offering to organize this survey OBJECTIVE To investigate the effectiveness and mechanism of recombinant human granulocyte-macrophage colony-stimulating factor ( rhGMCSF ) gel on wound debridement and healing of deep II thickness burn . METHODS Between December 2008 and December 2010 , 58 patients with deep II thickness burn , accorded with the inclusive criteria , were collected . There were 36 males and 22 females with an average age of 32.4 years ( range , 12 - 67 years ) . The causes were hot liquid in 38 cases and fire in 20 cases . The time from injury to treatment was 1 - 3 days ( mean , 2.1 days ) . In this r and omized , double-blind , and self-control study , all patients were r and omly divided into 2 groups , wounds were treated with rhGMCSF gel ( test group ) or gel matrix ( control group ) . There was no significant difference in wound area between 2 groups ( P > 0.05 ) . The time of completed removal eschar and the percentage of removal-area of eschar were recorded at 2 , 6 , 10 , 14 , and 18 days during healing process . The time of wound healing was also recorded . RESULTS Compared with control group , the necrotic tissues on the burn wound got soft in test group at 4 days after treatment . At 6 days , they loosened and eventually sloughed off . The wound bed presented in red and white , followed by rapidly growing granulation tissues . Except 18 days after treatment , there were significant differences in the percentage of removal-area of eschar between 2 groups ( P < 0.05 ) . The time of completed removal eschar in test group [ ( 7.71 + /- 2.76 ) days ] was significantly shorter than that in control group [ ( 14.71 + /- 3.63 ) days ] ( t = 13.726 , P = 0.000 ) . The time of wound healing in test group was ( 18.41 + /- 2.47 ) days , which was significantly shorter than that in control group [ ( 23.58 + /- 3.35 ) days ] ( t = 15.763 , P = 0.000 ) . CONCLUSION Compared with the gel matrix , the rhGMCSF gel may promote wound debridement and healing in deep II thickness burn OBJECTIVE To evaluate the efficacy and safety of recombinant human granulocyte-macrophage colony stimulating factor ( rhGM-CSF ) hydrogel in wound healing in patients with deep partial thickness burn . METHODS The study was a multicenter , r and omized , double-blind , placebo-controlled parallel clinical trial . Three hundred and twenty-one patients ( 302 cases finally fulfilled the protocol ) with deep partial thickness burn were divided into A group ( n = 200 , with treatment of rhGM-CSF hydrogel , 100 microg/10 g/100 cm2/d ) , C group ( n = 102,with treatment of placebo ) . Side-effect , systemic condition , wound healing time , wound healing rate , and total effective rate at different time points were observed . RESULTS There were no obvious differences in vital signs , wound secretion , wound edge reaction , blood and urine routine , liver and kidney function between two groups ( P > 0.05 ) . No side-effect was observed . The median wound healing time was 17 days in A group , which was obviously shorter than that in C group ( 20 days , P < 0.01 ) . The mean wound healing rate in A group was 24.5 % , 70.5 % , 95.3 % , 99.6 % respectively on 8th , 14th , 20th , 28th day after treatment , which were obviously higher than that in C group ( 15.1 % , 51.4 % , 84.6 % , 97.1 % , respectively , P < 0.01 ) . The total effective rates in A group on 8th , 14th , 20th day after treatment were also higher than that in C group ( P < 0.01 ) . CONCLUSION rhGM-CSF hydrogel can significantly accelerate wound healing in patients with deep partial thickness burn with certain safety A multicenter , double-blind , placebo-controlled trial was carried out to evaluate the intra-lesional infiltration of recombinant epidermal growth factor ( EGF ) in Wagner 's grade 3 or 4 diabetic foot ulcers ( DFUs ) . Subjects ( 149 ) were r and omised to receive EGF ( 75 or 25 microg ) or placebo  , three times per week for 8 weeks and st and ard good wound care . The main endpoint was granulation tissue covering > or = 50 % of the ulcer at 2 weeks . It was achieved by 19/48 controls versus 44/53 in the 75 microg group [ odds ratio ( OR ) : 7.5 ; 95 % confidence interval ( CI ) : 2.9 - 18.9 ] and 34/48 in the 25 microg group ( OR : 3.7 ; 1.6 - 8.7 ) . Secondary outcome variables such as end-of-treatment complete granulation response ( 28/48 controls , 46/53 with 75 microg and 34/48 with 25 microg EGF ) , time-to-complete response ( controls : 5 weeks ; both EGF dose groups : 3 weeks ) , and wound closure after follow-up ( 25/48 controls , 40/53 with 75 microg and 25/48 with 25 microg EGF ) were also treatment dependent . Multivariate analyses yielded that they were significantly enhanced by 75 microg EGF treatment and neuropathic versus ischemic ulcers . Most adverse events were mild and no drug-related severe adverse reactions were reported . It was concluded that recombinant human EGF ( rhEGF ) local injections offer a favourable risk-benefit balance in patients with advanced DFU
Growth factor ( GF ) therapy has shown promise in treating a variety of refractory wounds .
However , evidence supporting its routine use in burn injury remains uncertain .
We performed this systematic review and meta- analysis assessing r and omised controlled trials ( RCTs ) to investigate efficacy and safety of GFs in the management of partial-thickness burns .