This study developed an animal model of surgically wounded submandibular glands (SMGs) and investigated the effects of collagen gel with basic fibroblast growth factor (bFGF) on tissue regeneration of surgically w...This study developed an animal model of surgically wounded submandibular glands (SMGs) and investigated the effects of collagen gel with basic fibroblast growth factor (bFGF) on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF (bFGF group) or without bFGF (control group). In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day (AOD) 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, g-smooth muscle actin (αSMA), CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin 19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration.展开更多
Treatment with growth factors is an effective method to promote wound healing. Several growth factors have been used in wound treatment, including basic fibroblast growth factor (bFGF) discovered in the 1970s, platele...Treatment with growth factors is an effective method to promote wound healing. Several growth factors have been used in wound treatment, including basic fibroblast growth factor (bFGF) discovered in the 1970s, platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and bone morphogenetic protein (BMP). In 2001, Kaken Pharmaceutical Co., Ltd. launched Fiblast Spray in Japan. This product is a topical formulation containing recombinant human bFGF. It is used to treat decubitus ulcers and skin ulcers (burn ulcers and leg ulcers). There is increasing interest in its stimulatory effect on wound healing and its inhibitory effect on scar formation. Wound healing is a physiological phenomenon that involves a complex series of integrated cellular and biochemical responses, characterized by phases of hemostasis, inflammation, proliferation, and maturation. However, much of its detailed mechanism remains unknown. There have been many basic research studies on wound healing using cells and experimental animals. If findings can be used from such studies and clinical practice, development of even more effective treatments might be possible.展开更多
Wound complications are estimated to be affected in about 9% of TKA patients, which may increase the risk of deep periprosthetic infection and results in re-operation, joint fusion, or amputation. Here we have reporte...Wound complications are estimated to be affected in about 9% of TKA patients, which may increase the risk of deep periprosthetic infection and results in re-operation, joint fusion, or amputation. Here we have reported a female patient who suffered wound rupture due to early post-operation mobilization and weight-bearing. The wound dehiscence was successfully managed by applying recombinant basic fibroblast growth factor-2 and anti-infective treatment without removing prosthetic joint.展开更多
This research aims to develop a wound dressing composed of collagen (Col) and hyaluronic acid (HA) containing epidermal growth factor (EGF). First important issue is to contain EGF in the wound dressing in a stable st...This research aims to develop a wound dressing composed of collagen (Col) and hyaluronic acid (HA) containing epidermal growth factor (EGF). First important issue is to contain EGF in the wound dressing in a stable state. The sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of Col. Both sides of sponge were treated with ultraviolet (UV) irradiation to introduce intermolecular cross links between collagen molecules. This sponge was named Sponge-Col. Another sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of HA containing EGF. This sponge was named Sponge-HA/EGF. The wound dressing was manufactured by laminating Sponge-Col on the top, Sponge-HA/EGF in the middle, and Sponge-Col on the bottom to create a sandwich structure. This method can prevent the reducing of EGF activity due to UV irradiation for intermolecular cross-linking. Second important issue is to enable gradual release of EGF from the wound dressing. The elution behavior of this wound dressing was investigated by measuring the weight change after immersion in water for a predetermined time. This wound dressing showed initially fast elution and subsequent very slow elution properties. The upper layer and lower layer Sponge-Col enabled gradual release of the middle layer Sponge-HA/EGF. This result suggests that EGF contained in the wound dressing is gradually released together with HA from the wound dressing. Third important issue is to provide moist wound-healing environment. The upper layer and lower layer Sponge-Col can provide the wound dressing with high water absorption and long-term water retention properties.展开更多
Wound healing is a complex biologic event. Numerous growth factors are involved in the regulation of tissue repair and remodelling processes. In this study, several techniques were used to observe the effects of recom...Wound healing is a complex biologic event. Numerous growth factors are involved in the regulation of tissue repair and remodelling processes. In this study, several techniques were used to observe the effects of recombinant human epidermal growth factors (rh-EGF) on porcine partial-thickness burn wound healing. Healing rates of the burn wounds were quantitated by computer image analysis of the wound Pkotographs. Biopsies were taken for examining the cell DNA cycle by flow cytometry, and for observing the keratinocyte migration and degree of reepithelialization quantitated by anti-keratin antibodies. The results indicated that daily topical application of rh-EGF in suitable concentrations accelerated epithelial healing of partial-thickness burn wounds, and there was also a dose-dependent effect of rh-EGF on healing rates of the partial-thickness burn wounds.展开更多
Purpose: The usefulness of dissolving microneedles (DMs) for local skin therapy by basic fibroblast growth factor (bFGF) was studied in rats. Methods: We prepared four kinds of bFGF-loaded DMs, approximately 500 μm l...Purpose: The usefulness of dissolving microneedles (DMs) for local skin therapy by basic fibroblast growth factor (bFGF) was studied in rats. Methods: We prepared four kinds of bFGF-loaded DMs, approximately 500 μm length and 300 μm diameter at the bottom. Long-term stability and dissolution studies were performed by HPLC method. Pharmacokinetic and pharmacological evaluations were performed after administration of bFGF loaded DMs to rats. Results: The bFGF contents were 2.15 ± 0.07, 1.07 ± 0.04, 0.56 ± 0.07 and 0.12 ± 0.03 μg. The 100.2 ± 3.4%, 100.2 ± 3.3%, 99.3 ± 1.4% and 100.4 ± 3.0% of bFGF were recovered after 1, 3 and 6 months and 1 year incubation at 40°C. The bFGF was released from DMs within 5 min. In a pharmacokinetic study using 2.0 and 1.0 μg bFGF-loaded DMs, no systemic exposure of bFGF was detected. The initial bFGF concentrations in the rat skin tissue after administration of bFGF-loaded DMs to the hair-removed rat abdominal skin were 510.2 ± 20.1 ng/g wet weight for 2 μg bFGF DMs and 264.2 ± 56.5 ng/g wet weight for 1 μg DMs, declining slowly thereafter to 226.3 ± 33.5 and 105.1 ± 27.4 ng/g wet weight at 6 hr after administration. Good dose-dependency was observed. Pharmacological evaluation of bFGF-loaded DMs of 2.0, 1.0, 0.5, and 0.1 μg, in the wound healing rat model, all used DMs, but 0.1 μg DMs, showed good healing effects. Considered collectively, these results suggest the usefulness of bFGF-loaded DMs for local therapy of skin wound disease.展开更多
This study is to investigate the effect of FK506 on expression of hepatocyte growth factor (HGF) in rats' spinal cord following peripheral nerve injury and to elucidate the mechanisms for neuroprotective property o...This study is to investigate the effect of FK506 on expression of hepatocyte growth factor (HGF) in rats' spinal cord following peripheral nerve injury and to elucidate the mechanisms for neuroprotective property of FK506. Fifty male rats were randomly divided into normal group, injury group and treatment group. Models of peripheral nerve injury were established by bilateral transection of sciatic nerve 0.5 cm distal to piriform muscle. Then the treatment group received subcutaneous injection of FK506 (1 mg/kg) at the back of neck, while the injury group was given 0.9% saline. The L4-6 spinal cords were harvested at various time points after the surgery. Western blotting and immunofluorescent staining were used to detect the level and position of HGF in spinal cord. Immunofluorescent staining showed that HGF-positive neurons were located in anterior horn, intermediate zone and posterior horn of gray matter in normal spinal cord. Western blotting revealed that there was no significant difference in the expressions of HGF between the injury group and the normal group, while the expression of HGF was significantly higher in the treatment group than in the injury group 7 and 14 days after surgery. It is suggested that peripheral nerve injury does not result in up-regulation of the expression of HGF in spinal cord, while FK506 may induce high expression of endogenous HGF after injury thereby protecting neurons and promoting axonal outgrowth.展开更多
Objective To explore the glycation of basic fibroblast grow th factor( bFGF) in diabetic skin.Methods The abdom inal full-thickness skin tissues from 58 patients( 29 diabetic and 29 non-diabetic) aged 40 to69 years an...Objective To explore the glycation of basic fibroblast grow th factor( bFGF) in diabetic skin.Methods The abdom inal full-thickness skin tissues from 58 patients( 29 diabetic and 29 non-diabetic) aged 40 to69 years and granulation tissues from 15 patients( 8 diabetic and 7 non-diabetic) aged 50 to 59 were analyzed.The proportion of advanced glycation end products( AGEs)-b FG F intotal b FGF was measured with co-immunoprecipitation and the histological characteristics of wound skin were detected with hem atoxylin and eosin staining. The cell viability, apoptosis, and angiogenesis of human derm al m icrovascular endothelial cells( HDMECs) after exposure to AG Es-b FG For bFGF were measured with cell counting kit-8, flow cytom etry,and tube form ation assay, respectively. Results The proportion of AG Es-b FG F in total b FG F showed agedependent increaseboth in diabetic and non-diabetic skin. As com pared with non-diabetic skin, the constituent ratio in diabetic skin increased significantly in the equal age-group, and the same result could be obtained in granulation tissues from patients aged 50 to 59. The proportion of AG Es-b FG F in diabetic granulation was low er than that in diabetic skin from patients aged 50 to 59. H istological analysis show ed few er vessels in diabetic skin wound. In vitro, the viability and vascularization of H D M EC s were promoted by b FG F and inhibited after exposure to AGEs-bFGF for 7d. Conclusion The present study indicates that one cause for im paired wound healing in diabetic skin could be the glycated b FG F and its changed angiogenic function.展开更多
AIM:To investigate the healing process after severe corneal epithelial damage in rats treated with mesenchymal stem cells(MSCs)cultured with or without keratinocyte growth factor(KGF-2)and autologous serum(AS)on amnio...AIM:To investigate the healing process after severe corneal epithelial damage in rats treated with mesenchymal stem cells(MSCs)cultured with or without keratinocyte growth factor(KGF-2)and autologous serum(AS)on amniotic membrane(AM).Many patients are blind and devastated by severe ocular surface diseases due to limbal stem cell deficiency.Bone marrow-derived MSCs are potential sources for cellbased tissue engineering to repair or replace the corneal tissue,having the potential to differentiate to epithelial cells.METHODS:The study included 5 groups each including 10 female'Sprague Dawley'rats in addition to20 male rats used as bone marrow donors.Group I rats received AM+MSCs,Group II rats AM+MSCs cultured with KGF-2,Group III rats AM+MSCs cultured with KGF-2+AS,Group IV rats only AM and Group V rats,none.AS was derived from blood drawn from male rats and bone marrow was obtained from the femur and tibia bones of the same animals.Therapeutic effect was evaluated with clinical,histopathological and immunohistochemical assessment.MSC engraftment was demonstrated via detection of donor genotype(Y+)in the recipient tissue(X)with polymerase chain reaction.RESULTS:Corneal healing was significantly better in Groups I-III rats treated with MSC transplantation compared to Group IV and Group V rats with supportive treatment only.The best results were obtained in Group III rats with 90%transparency,70%lack of neovascularization,and 100%epithelium damage limited to less than 1/4 of cornea.CONCLUSION:We suggest that culture of MSCs with KGF-2 and AS on AM is effective in corneal repair in case of irreversible damage to limbal stem cells.展开更多
Aim: To evaluate the factors influencing fascial wound dehiscence after midline laparotomy in the patients of perforation peritonitis with an emphasis on measurement of “intra-abdominal” pressure (IAP) and fascial t...Aim: To evaluate the factors influencing fascial wound dehiscence after midline laparotomy in the patients of perforation peritonitis with an emphasis on measurement of “intra-abdominal” pressure (IAP) and fascial transforming growth factor-beta (TGF-beta). Methods: Hundred eligible adult patients with the diagnosis of perforation peritonitis who underwent emergency exploratory laparotomy were prospectively recruited. Forty five patients who developed midline abdominal wound dehiscence were compared with 55 patients without dehiscence. Results: The variables that were significantly associated with wound dehiscence include anemia, hypo proteinemia, duration of surgery, prolonged postoperative ileus, wound infection and postoperative pulmonary infection. Age, gender, jaundice, cause of peritonitis, wound contamination and types of surgery were non significant variables. The mean IAP value in the patients with dehiscence was significantly higher than “non-dehiscence” group (p = 0.000). The patients with wound dehiscence strongly expressed TGF-beta on the day of burst. Conclusion: The patients of peritonitis undergoing prolonged surgery in the presence of risk factors like anemia, hypo proteinemia, postoperative ileus, wound infection and postoperative pulmonary infection have high risk of abdominal wound dehiscence.展开更多
Objective To scrutinize the effect of growth factors resulting from the intermingled skin graft onwound healing. Methods By means of RT-PCR technique, mRNA expressions of TGFα, TGFβ1, PDGF andbFGF of autografts and ...Objective To scrutinize the effect of growth factors resulting from the intermingled skin graft onwound healing. Methods By means of RT-PCR technique, mRNA expressions of TGFα, TGFβ1, PDGF andbFGF of autografts and allografts on burnt rats were quantitatively analysed. Results (1) mRNA expressions ofall the four growth factors mentioned above were found both in allografts and autografts, the expressions beinghigher in autografts than allografts; (2) In autografts, TGFα expression began to rise from second post transplantday (D2), reaching a peak on D18,. TGFβ1 expression gained a high level on D2 and had itS peak on D18; PDGFexpression had its peak on D4, rebounding on D25; bFGF expression, exceedingly high on D2, dropped andrebounded in the same manner as in PDGF; (3) In the early stage of the wound healing, mRNA expression of thefour growth factors was lower in allografts, rising up in varying degrees thereafter. Conclusion (1) Graftsurvival took place both in autografts and allografts, with the former pederming better than the latter; (2) Thecombining action of growth factors that reached the affected area through autosecretion and bysecretion probablypromoted the healing of the burn wound, following signal transmission channels; (3) Rejection, which occurred inallogralts, was responsible for the decreasing viability of allografts and their replacement by the host skin.展开更多
This study aimed to explore the role of mechanical tension in hypertrophic scars and the change in nerve density using hematoxylin-eosin staining and S100 immunohistochemistry, and to observe the expression of nerve g...This study aimed to explore the role of mechanical tension in hypertrophic scars and the change in nerve density using hematoxylin-eosin staining and S100 immunohistochemistry, and to observe the expression of nerve growth factor by western blot analysis. The results demonstrated that mechanical tension contributed to the formation of a hyperplastic scar in the back skin of rats, in conjunction with increases in both nerve density and nerve growth factor expression in the scar tissue. These experimental findings indicate that the cutaneous nervous system plays a role in hypertrophic scar formation caused by mechanical tension.展开更多
This clinical trial aimed to evaluate the efficacy and safety of a novel wound dressing composed of hyaluronic acid (HA) and collagen (Col) containing epidermal growth factor (EGF), referred to as EGF-wound dressing. ...This clinical trial aimed to evaluate the efficacy and safety of a novel wound dressing composed of hyaluronic acid (HA) and collagen (Col) containing epidermal growth factor (EGF), referred to as EGF-wound dressing. EGF-wound dressing was prepared by freeze-drying a mixed aqueous solution of high-molecular-weight HA, low-molecular-weight HA and heat-denatured Col containing EGF. EGF-wound dressing was applied to skin defects, such as intractable skin ulcers, burn ulcers, traumatic skin defects and skin donor-site wounds. The dressing was changed twice a week for a period of 6 weeks or longer, if necessary. The primary endpoints were size of wound area, formation of granulation tissue, extent of epithelialization, infection control and macroscopic appearance. Effectiveness, safety and overall clinical evaluation were scored by plastic surgeons, as authorized by the Japanese Society of Plastic and Reconstructive Surgery. This study was registered with the University Hospital Medical Information Network (UMIN0000005264). Healthy granulation tissue and rapid epithelialization were observed for a given period after application of EGF-wound dressing onto the wounds. Most cases were assessed as having achieved good or excellent results. This clinical study demonstrated that EGF-wound dressing was beneficial in the treatment of various skin defects.展开更多
In order to investigate the promoting effect of low-intensity treadmill exercise on rat dorsal wound healing and the mechanism, 20 Sprague-Dawley rats were randomly divided into two groups: exercise group(Ex) and n...In order to investigate the promoting effect of low-intensity treadmill exercise on rat dorsal wound healing and the mechanism, 20 Sprague-Dawley rats were randomly divided into two groups: exercise group(Ex) and non-exercise group(non-ex). The rats in Ex group were given treadmill exercise for one month, and those in non-ex group raised on the same conditions without treadmill exercise. Both groups received dorsal wound operation with free access to food and water. By two-week continuous observation and recording of the wound area, the healing rate was analyzed. The blood sample was collected at day 14 post-operation via cardiac puncture for determination of the number of endothelial progenitor cells(EPCs) by flow cytometry, and the concentrations of relevant cytokines such as basic fibroblast growth factor(b FGF), endothelial nitric oxide synthase(e NOS) and vascular endothelial growth factor(VEGF) were measured by ELISA. The skin tissue around the wound was dissected to observe the vascular density under the microscope after HE staining, to detect the m RNA level of VEGFR2 and angiopoietin-1(Ang-1) receptor using RT-q PCR, and protein expression of α-smooth muscle actin(αSMA) and type collagenⅢ(ColⅢ) using Western blotting. It was found that the wound area in Ex group was smaller at the same time point than in non-ex group. The number of circulating EPCs was greater and the concentrations of vasoactive factors such as VEGF, e NOS and b FGF were higher in Ex group than in non-ex group. HE staining displayed a higher vessel density in Ex group than in non-ex group. Moreover, the m RNA expression of VEGFR2 and Ang-1 detected in the wound tissue in Ex group was higher than in non-ex group. Meanwhile, the protein expression of αSMA and Col Ⅲwas more abundant in Ex group than in non-ex group. Conclusively, the above results demonstrate Ex rats had a higher wound healing rate, suggesting low-intensity treadmill exercise accelerates wound healing. The present work may provide some hint for future study of treating refractory wound.展开更多
BACKGROUND Laparoscopic resection of the pancreatic body and tail is the predominant methodology to remove lesions in these locations;its safety and surgical planning are relatively mature, but it remains a complex an...BACKGROUND Laparoscopic resection of the pancreatic body and tail is the predominant methodology to remove lesions in these locations;its safety and surgical planning are relatively mature, but it remains a complex and high-precision surgical operation, requiring abundant experience and skills in laparoscopic surgery, with a 10% rate of complications. AIM To verify the feasibility and safety, as well as to examine the complications of endoscopic pancreatectomy and healing mechanisms of pancreatic wounds after endoscopic resection. METHODS Transgastric endoscopic resections of varying sizes of pancreases were performed in 15 healthy Bama miniature pigs. The technical success rate, the incidence of serious complications, and the survival of the animals were studied. The healing of the wounds was evaluated by sacrificing the animals at various time points. Finally, the expression of transforming growth factor-β1 and Smad3/Smad7 in the surgical site was examined by immunohistochemistry to explore the role of these factors in wound healing of the pancreas. RESULTS Partial and total resections were successfully performed in two groups of animals, respectively. The technical success rate and the survival rate of the pigs were both 100%. We obtained 12 pancreatic tissue samples by endoscopic resection. The pancreatic wounds were closed with metal clips in one group and the wounds healed well by forming scars. There was a small amount of pancreatic leakage in the other group, but it can be fully encapsulated. The level of transforming growth factor-β1 (TGF-β1) in the wounds increased during the inflammatory and fibrous hyperplasia phases, and decreased in the scar phase. The expression of Smad3 paralleled that of TGF-β1, while the expression of Smad7 had an inverse relationship with the expression of TGF-β1. CONCLUSION Purely transgastric endoscopic resection of the pancreas is a safe, effective, and feasible procedure, but the incidence of pancreatic leakage in total pancreatic tail resection is high. The expression of TGF-β1 and Smad3/Samd7 is related to the progression of pancreatic wound healing.展开更多
文摘This study developed an animal model of surgically wounded submandibular glands (SMGs) and investigated the effects of collagen gel with basic fibroblast growth factor (bFGF) on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF (bFGF group) or without bFGF (control group). In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day (AOD) 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, g-smooth muscle actin (αSMA), CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin 19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration.
文摘Treatment with growth factors is an effective method to promote wound healing. Several growth factors have been used in wound treatment, including basic fibroblast growth factor (bFGF) discovered in the 1970s, platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and bone morphogenetic protein (BMP). In 2001, Kaken Pharmaceutical Co., Ltd. launched Fiblast Spray in Japan. This product is a topical formulation containing recombinant human bFGF. It is used to treat decubitus ulcers and skin ulcers (burn ulcers and leg ulcers). There is increasing interest in its stimulatory effect on wound healing and its inhibitory effect on scar formation. Wound healing is a physiological phenomenon that involves a complex series of integrated cellular and biochemical responses, characterized by phases of hemostasis, inflammation, proliferation, and maturation. However, much of its detailed mechanism remains unknown. There have been many basic research studies on wound healing using cells and experimental animals. If findings can be used from such studies and clinical practice, development of even more effective treatments might be possible.
文摘Wound complications are estimated to be affected in about 9% of TKA patients, which may increase the risk of deep periprosthetic infection and results in re-operation, joint fusion, or amputation. Here we have reported a female patient who suffered wound rupture due to early post-operation mobilization and weight-bearing. The wound dehiscence was successfully managed by applying recombinant basic fibroblast growth factor-2 and anti-infective treatment without removing prosthetic joint.
文摘This research aims to develop a wound dressing composed of collagen (Col) and hyaluronic acid (HA) containing epidermal growth factor (EGF). First important issue is to contain EGF in the wound dressing in a stable state. The sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of Col. Both sides of sponge were treated with ultraviolet (UV) irradiation to introduce intermolecular cross links between collagen molecules. This sponge was named Sponge-Col. Another sheet-shaped sponge was manufactured by freeze-vacuum drying an aqueous solution of HA containing EGF. This sponge was named Sponge-HA/EGF. The wound dressing was manufactured by laminating Sponge-Col on the top, Sponge-HA/EGF in the middle, and Sponge-Col on the bottom to create a sandwich structure. This method can prevent the reducing of EGF activity due to UV irradiation for intermolecular cross-linking. Second important issue is to enable gradual release of EGF from the wound dressing. The elution behavior of this wound dressing was investigated by measuring the weight change after immersion in water for a predetermined time. This wound dressing showed initially fast elution and subsequent very slow elution properties. The upper layer and lower layer Sponge-Col enabled gradual release of the middle layer Sponge-HA/EGF. This result suggests that EGF contained in the wound dressing is gradually released together with HA from the wound dressing. Third important issue is to provide moist wound-healing environment. The upper layer and lower layer Sponge-Col can provide the wound dressing with high water absorption and long-term water retention properties.
文摘Wound healing is a complex biologic event. Numerous growth factors are involved in the regulation of tissue repair and remodelling processes. In this study, several techniques were used to observe the effects of recombinant human epidermal growth factors (rh-EGF) on porcine partial-thickness burn wound healing. Healing rates of the burn wounds were quantitated by computer image analysis of the wound Pkotographs. Biopsies were taken for examining the cell DNA cycle by flow cytometry, and for observing the keratinocyte migration and degree of reepithelialization quantitated by anti-keratin antibodies. The results indicated that daily topical application of rh-EGF in suitable concentrations accelerated epithelial healing of partial-thickness burn wounds, and there was also a dose-dependent effect of rh-EGF on healing rates of the partial-thickness burn wounds.
文摘Purpose: The usefulness of dissolving microneedles (DMs) for local skin therapy by basic fibroblast growth factor (bFGF) was studied in rats. Methods: We prepared four kinds of bFGF-loaded DMs, approximately 500 μm length and 300 μm diameter at the bottom. Long-term stability and dissolution studies were performed by HPLC method. Pharmacokinetic and pharmacological evaluations were performed after administration of bFGF loaded DMs to rats. Results: The bFGF contents were 2.15 ± 0.07, 1.07 ± 0.04, 0.56 ± 0.07 and 0.12 ± 0.03 μg. The 100.2 ± 3.4%, 100.2 ± 3.3%, 99.3 ± 1.4% and 100.4 ± 3.0% of bFGF were recovered after 1, 3 and 6 months and 1 year incubation at 40°C. The bFGF was released from DMs within 5 min. In a pharmacokinetic study using 2.0 and 1.0 μg bFGF-loaded DMs, no systemic exposure of bFGF was detected. The initial bFGF concentrations in the rat skin tissue after administration of bFGF-loaded DMs to the hair-removed rat abdominal skin were 510.2 ± 20.1 ng/g wet weight for 2 μg bFGF DMs and 264.2 ± 56.5 ng/g wet weight for 1 μg DMs, declining slowly thereafter to 226.3 ± 33.5 and 105.1 ± 27.4 ng/g wet weight at 6 hr after administration. Good dose-dependency was observed. Pharmacological evaluation of bFGF-loaded DMs of 2.0, 1.0, 0.5, and 0.1 μg, in the wound healing rat model, all used DMs, but 0.1 μg DMs, showed good healing effects. Considered collectively, these results suggest the usefulness of bFGF-loaded DMs for local therapy of skin wound disease.
文摘This study is to investigate the effect of FK506 on expression of hepatocyte growth factor (HGF) in rats' spinal cord following peripheral nerve injury and to elucidate the mechanisms for neuroprotective property of FK506. Fifty male rats were randomly divided into normal group, injury group and treatment group. Models of peripheral nerve injury were established by bilateral transection of sciatic nerve 0.5 cm distal to piriform muscle. Then the treatment group received subcutaneous injection of FK506 (1 mg/kg) at the back of neck, while the injury group was given 0.9% saline. The L4-6 spinal cords were harvested at various time points after the surgery. Western blotting and immunofluorescent staining were used to detect the level and position of HGF in spinal cord. Immunofluorescent staining showed that HGF-positive neurons were located in anterior horn, intermediate zone and posterior horn of gray matter in normal spinal cord. Western blotting revealed that there was no significant difference in the expressions of HGF between the injury group and the normal group, while the expression of HGF was significantly higher in the treatment group than in the injury group 7 and 14 days after surgery. It is suggested that peripheral nerve injury does not result in up-regulation of the expression of HGF in spinal cord, while FK506 may induce high expression of endogenous HGF after injury thereby protecting neurons and promoting axonal outgrowth.
基金National Natural Science Foundation of China(81071568,81272111)National Science and Technology Support Plan(2012BAI11B00)
文摘Objective To explore the glycation of basic fibroblast grow th factor( bFGF) in diabetic skin.Methods The abdom inal full-thickness skin tissues from 58 patients( 29 diabetic and 29 non-diabetic) aged 40 to69 years and granulation tissues from 15 patients( 8 diabetic and 7 non-diabetic) aged 50 to 59 were analyzed.The proportion of advanced glycation end products( AGEs)-b FG F intotal b FGF was measured with co-immunoprecipitation and the histological characteristics of wound skin were detected with hem atoxylin and eosin staining. The cell viability, apoptosis, and angiogenesis of human derm al m icrovascular endothelial cells( HDMECs) after exposure to AG Es-b FG For bFGF were measured with cell counting kit-8, flow cytom etry,and tube form ation assay, respectively. Results The proportion of AG Es-b FG F in total b FG F showed agedependent increaseboth in diabetic and non-diabetic skin. As com pared with non-diabetic skin, the constituent ratio in diabetic skin increased significantly in the equal age-group, and the same result could be obtained in granulation tissues from patients aged 50 to 59. The proportion of AG Es-b FG F in diabetic granulation was low er than that in diabetic skin from patients aged 50 to 59. H istological analysis show ed few er vessels in diabetic skin wound. In vitro, the viability and vascularization of H D M EC s were promoted by b FG F and inhibited after exposure to AGEs-bFGF for 7d. Conclusion The present study indicates that one cause for im paired wound healing in diabetic skin could be the glycated b FG F and its changed angiogenic function.
文摘AIM:To investigate the healing process after severe corneal epithelial damage in rats treated with mesenchymal stem cells(MSCs)cultured with or without keratinocyte growth factor(KGF-2)and autologous serum(AS)on amniotic membrane(AM).Many patients are blind and devastated by severe ocular surface diseases due to limbal stem cell deficiency.Bone marrow-derived MSCs are potential sources for cellbased tissue engineering to repair or replace the corneal tissue,having the potential to differentiate to epithelial cells.METHODS:The study included 5 groups each including 10 female'Sprague Dawley'rats in addition to20 male rats used as bone marrow donors.Group I rats received AM+MSCs,Group II rats AM+MSCs cultured with KGF-2,Group III rats AM+MSCs cultured with KGF-2+AS,Group IV rats only AM and Group V rats,none.AS was derived from blood drawn from male rats and bone marrow was obtained from the femur and tibia bones of the same animals.Therapeutic effect was evaluated with clinical,histopathological and immunohistochemical assessment.MSC engraftment was demonstrated via detection of donor genotype(Y+)in the recipient tissue(X)with polymerase chain reaction.RESULTS:Corneal healing was significantly better in Groups I-III rats treated with MSC transplantation compared to Group IV and Group V rats with supportive treatment only.The best results were obtained in Group III rats with 90%transparency,70%lack of neovascularization,and 100%epithelium damage limited to less than 1/4 of cornea.CONCLUSION:We suggest that culture of MSCs with KGF-2 and AS on AM is effective in corneal repair in case of irreversible damage to limbal stem cells.
文摘Aim: To evaluate the factors influencing fascial wound dehiscence after midline laparotomy in the patients of perforation peritonitis with an emphasis on measurement of “intra-abdominal” pressure (IAP) and fascial transforming growth factor-beta (TGF-beta). Methods: Hundred eligible adult patients with the diagnosis of perforation peritonitis who underwent emergency exploratory laparotomy were prospectively recruited. Forty five patients who developed midline abdominal wound dehiscence were compared with 55 patients without dehiscence. Results: The variables that were significantly associated with wound dehiscence include anemia, hypo proteinemia, duration of surgery, prolonged postoperative ileus, wound infection and postoperative pulmonary infection. Age, gender, jaundice, cause of peritonitis, wound contamination and types of surgery were non significant variables. The mean IAP value in the patients with dehiscence was significantly higher than “non-dehiscence” group (p = 0.000). The patients with wound dehiscence strongly expressed TGF-beta on the day of burst. Conclusion: The patients of peritonitis undergoing prolonged surgery in the presence of risk factors like anemia, hypo proteinemia, postoperative ileus, wound infection and postoperative pulmonary infection have high risk of abdominal wound dehiscence.
文摘Objective To scrutinize the effect of growth factors resulting from the intermingled skin graft onwound healing. Methods By means of RT-PCR technique, mRNA expressions of TGFα, TGFβ1, PDGF andbFGF of autografts and allografts on burnt rats were quantitatively analysed. Results (1) mRNA expressions ofall the four growth factors mentioned above were found both in allografts and autografts, the expressions beinghigher in autografts than allografts; (2) In autografts, TGFα expression began to rise from second post transplantday (D2), reaching a peak on D18,. TGFβ1 expression gained a high level on D2 and had itS peak on D18; PDGFexpression had its peak on D4, rebounding on D25; bFGF expression, exceedingly high on D2, dropped andrebounded in the same manner as in PDGF; (3) In the early stage of the wound healing, mRNA expression of thefour growth factors was lower in allografts, rising up in varying degrees thereafter. Conclusion (1) Graftsurvival took place both in autografts and allografts, with the former pederming better than the latter; (2) Thecombining action of growth factors that reached the affected area through autosecretion and bysecretion probablypromoted the healing of the burn wound, following signal transmission channels; (3) Rejection, which occurred inallogralts, was responsible for the decreasing viability of allografts and their replacement by the host skin.
基金supported by the Shandong Excellent Young Scientist Research Award Fund of the Natural Science Foundation of Shandong Province, No. BS2009YY043Shandong Medical and Health Science and Technology Development Program for Youth Fund, No. 2009QZ023the National Natural Science Foundation of China, No. 81272099
文摘This study aimed to explore the role of mechanical tension in hypertrophic scars and the change in nerve density using hematoxylin-eosin staining and S100 immunohistochemistry, and to observe the expression of nerve growth factor by western blot analysis. The results demonstrated that mechanical tension contributed to the formation of a hyperplastic scar in the back skin of rats, in conjunction with increases in both nerve density and nerve growth factor expression in the scar tissue. These experimental findings indicate that the cutaneous nervous system plays a role in hypertrophic scar formation caused by mechanical tension.
文摘This clinical trial aimed to evaluate the efficacy and safety of a novel wound dressing composed of hyaluronic acid (HA) and collagen (Col) containing epidermal growth factor (EGF), referred to as EGF-wound dressing. EGF-wound dressing was prepared by freeze-drying a mixed aqueous solution of high-molecular-weight HA, low-molecular-weight HA and heat-denatured Col containing EGF. EGF-wound dressing was applied to skin defects, such as intractable skin ulcers, burn ulcers, traumatic skin defects and skin donor-site wounds. The dressing was changed twice a week for a period of 6 weeks or longer, if necessary. The primary endpoints were size of wound area, formation of granulation tissue, extent of epithelialization, infection control and macroscopic appearance. Effectiveness, safety and overall clinical evaluation were scored by plastic surgeons, as authorized by the Japanese Society of Plastic and Reconstructive Surgery. This study was registered with the University Hospital Medical Information Network (UMIN0000005264). Healthy granulation tissue and rapid epithelialization were observed for a given period after application of EGF-wound dressing onto the wounds. Most cases were assessed as having achieved good or excellent results. This clinical study demonstrated that EGF-wound dressing was beneficial in the treatment of various skin defects.
基金supported by the National Natural Science Foundation of China(No.81141077 and No.81271968)
文摘In order to investigate the promoting effect of low-intensity treadmill exercise on rat dorsal wound healing and the mechanism, 20 Sprague-Dawley rats were randomly divided into two groups: exercise group(Ex) and non-exercise group(non-ex). The rats in Ex group were given treadmill exercise for one month, and those in non-ex group raised on the same conditions without treadmill exercise. Both groups received dorsal wound operation with free access to food and water. By two-week continuous observation and recording of the wound area, the healing rate was analyzed. The blood sample was collected at day 14 post-operation via cardiac puncture for determination of the number of endothelial progenitor cells(EPCs) by flow cytometry, and the concentrations of relevant cytokines such as basic fibroblast growth factor(b FGF), endothelial nitric oxide synthase(e NOS) and vascular endothelial growth factor(VEGF) were measured by ELISA. The skin tissue around the wound was dissected to observe the vascular density under the microscope after HE staining, to detect the m RNA level of VEGFR2 and angiopoietin-1(Ang-1) receptor using RT-q PCR, and protein expression of α-smooth muscle actin(αSMA) and type collagenⅢ(ColⅢ) using Western blotting. It was found that the wound area in Ex group was smaller at the same time point than in non-ex group. The number of circulating EPCs was greater and the concentrations of vasoactive factors such as VEGF, e NOS and b FGF were higher in Ex group than in non-ex group. HE staining displayed a higher vessel density in Ex group than in non-ex group. Moreover, the m RNA expression of VEGFR2 and Ang-1 detected in the wound tissue in Ex group was higher than in non-ex group. Meanwhile, the protein expression of αSMA and Col Ⅲwas more abundant in Ex group than in non-ex group. Conclusively, the above results demonstrate Ex rats had a higher wound healing rate, suggesting low-intensity treadmill exercise accelerates wound healing. The present work may provide some hint for future study of treating refractory wound.
文摘BACKGROUND Laparoscopic resection of the pancreatic body and tail is the predominant methodology to remove lesions in these locations;its safety and surgical planning are relatively mature, but it remains a complex and high-precision surgical operation, requiring abundant experience and skills in laparoscopic surgery, with a 10% rate of complications. AIM To verify the feasibility and safety, as well as to examine the complications of endoscopic pancreatectomy and healing mechanisms of pancreatic wounds after endoscopic resection. METHODS Transgastric endoscopic resections of varying sizes of pancreases were performed in 15 healthy Bama miniature pigs. The technical success rate, the incidence of serious complications, and the survival of the animals were studied. The healing of the wounds was evaluated by sacrificing the animals at various time points. Finally, the expression of transforming growth factor-β1 and Smad3/Smad7 in the surgical site was examined by immunohistochemistry to explore the role of these factors in wound healing of the pancreas. RESULTS Partial and total resections were successfully performed in two groups of animals, respectively. The technical success rate and the survival rate of the pigs were both 100%. We obtained 12 pancreatic tissue samples by endoscopic resection. The pancreatic wounds were closed with metal clips in one group and the wounds healed well by forming scars. There was a small amount of pancreatic leakage in the other group, but it can be fully encapsulated. The level of transforming growth factor-β1 (TGF-β1) in the wounds increased during the inflammatory and fibrous hyperplasia phases, and decreased in the scar phase. The expression of Smad3 paralleled that of TGF-β1, while the expression of Smad7 had an inverse relationship with the expression of TGF-β1. CONCLUSION Purely transgastric endoscopic resection of the pancreas is a safe, effective, and feasible procedure, but the incidence of pancreatic leakage in total pancreatic tail resection is high. The expression of TGF-β1 and Smad3/Samd7 is related to the progression of pancreatic wound healing.