<span style="line-height:1.5;font-family:Verdana;">This research aims to obtain useful information for development of medical devices such as wound dressing and tissue anti-adhesive product, using a sp...<span style="line-height:1.5;font-family:Verdana;">This research aims to obtain useful information for development of medical devices such as wound dressing and tissue anti-adhesive product, using a spongy sheet composed of hyaluronic acid (HA) and collagen (Col). The spongy sheets were manufactured by freeze vacuum drying of HA and Col aqueous solution, followed by UV irradiation to introduce intermolecular crosslinks between Col molecules. These spongy sheets are referred to as Sponge-A (ratio of HA/Col = 5/1) and Sponge-B (ratio of HA/Col = 5/5). Both surfaces of Sponge-A and Sponge-B treated with UV irradiation for 15 minutes are referred to as Sponge-A-15 and Sponge-B-15, respectively. The weight change of spongy sheet was determined by immersing a peace of spongy sheet in water at 37°</span><span style="line-height:1.5;font-family:Verdana;">C</span><span style="line-height:1.5;font-family:Verdana;">. The weight of sponge-A-15 collected 1/2, 1, 3, 7 days after immersion in water was 63.5%, 62.1%, 56.6%, 54.4% of the original weight, respectively. The weight of Sponge-B-15 was 78.3%, 76.7%, 79.1%, 71.9% of the original weight, respectively. The weight change of spongy sheet was determined by immersing a peace of spongy sheet in water containing collagenase at 37°</span><span style="line-height:1.5;font-family:Verdana;">C</span><span style="line-height:1.5;font-family:Verdana;">. The weight of Sponge-A-15 collected 6, 8, 10, 12 hours after immersion in water containing collagenase (0.0005</span><span "="" style="line-height:1.5;"> </span><span style="line-height:1.5;font-family:Verdana;">w/v%) was 65.7%, 59.8%, 57.9%, 55.2% of the original weight, respectively. The weight of Sponge-B-15 was 63.5%, 52.1%, 42.0%, 43.2% of the original weight, respectively. This spongy sheet is considered to have the unique structure, where HA molecules are entrapped in an intermolecular cross-linked network structure of Col molecules. When immersed in water containing collagenase, the weight loss of spongy sheet is accelerated by easy extraction of HA molecules from the enzymatic degraded Col network structure. The performance of wound dressing and tissue anti-adhesive product is considered to depend on appropriate ratio of HA and Col, and also on appropriate rate of intermolecular crosslinks between Col molecules. These findings obtained in this study provide useful information for product development such as wound dressing and tissue anti-adhesive product.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
This study aims to develop various types of collagen devices for use in oral surgery. The targets are the sheet-shaped sponges to cover mucosal defect wounds (product-1) and gingival defect wounds (product-2) and the ...This study aims to develop various types of collagen devices for use in oral surgery. The targets are the sheet-shaped sponges to cover mucosal defect wounds (product-1) and gingival defect wounds (product-2) and the cylindrical sponge to fill tooth extraction sockets (product-3). The sheet-shaped sponges were manufactured by freeze-vacuum drying the aqueous solution of collagen (Col) and heat-denatured collagen (Col’) at a composition ratio of 2/1, 1/1 or 1/2. Both surfaces of the sheet-shaped sponge were treated by ultraviolet (UV) irradiation for 5, 10 or 15 minutes to introduce intermolecular crosslinks between collagen molecules. The elution behavior of each collagen sponge was investigated by immersing the sponge in water for a predetermined time and then by measuring the weight change. The collagen sponge composed of Col and Col’ with a composition ratio of 2/1 that was treated by UV irradiation for 15 minutes showed very slow elution properties. This sheet-shaped sponge is the top candidate for product-1. The collagen sponge composed of Col and Col’ with a composition ratio of 2/1 that was treated by UV irradiation for 5 minutes showed slightly fast elution properties. This sheet-shaped sponge is the top candidate for product-2. Next, the cylindrical sponge was manufactured by freeze-vacuum drying the aqueous solution of Col and Col’ at a composition ratio of 2/1. Both sides of the cylindrical sponge were treated by UV irradiation for 15 minutes. This sponge showed initially fast elution properties and subsequent very slow elution properties. This cylindrical sponge is a good candidate for product-3. As a basic design, the sheet-shaped sponge and the cylindrical sponge should be biodegraded and absorbed by the time new tissue formation is completed.展开更多
This study aimed to investigate the potential of cultured dermal substitute (CDS) to release angiogenic growth factors when laminated with a membrane containing epidermal growth factor (EGF) as a top dressing. Membran...This study aimed to investigate the potential of cultured dermal substitute (CDS) to release angiogenic growth factors when laminated with a membrane containing epidermal growth factor (EGF) as a top dressing. Membranes were prepared by air-drying a solution of hyaluronic acid (HA) and collagen (Col) with or without EGF. Membranes were designed to contain EGF at concentrations of 0, 0.1, 0.2 or 0.5 μg/cm2. CDS was prepared by incorporating fibroblasts into a collagen gel combined with a cross-linked HA spongy matrix, followed by culturing for 5 days. CDS was designed to contain fibroblasts at a density of 2 × 105 (Group I) or 4 × 105 cells/cm2> (Group II). CDS was elevated at the interface between air and culture medium, on the top of which each membrane was placed. This culture system was employed as a wound surface model. Metabolic activity of the fibroblasts in the CDS cultured for 7 days on a wound surface model was measured by MTT assay. The amounts of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) after 7 days of cultivation were measured by using ELISA. Membranes containing EGF ranging from 0.1 to 0.5 μg/cm2> facilitated production of both VEGF and HGF, as compared with control membranes without EGF. However, a membrane containing EGF at a concentration of 0.5 μg/cm2> failed to facilitate fibroblast cytokine production in Group I. These results demonstrated that the EGF-incorporating membrane was able to stimulate fibroblasts in the CDS to synthesize an increased amount of VEGF and HGF in a dose-dependent manner.展开更多
This study aims to develop collagen-based hemostatic materials. The sheet-shaped collagen sponge was manufactured by freeze-vacuum drying the aqueous solution of collagen (Col) and heat-denatured collagen (Col’) at a...This study aims to develop collagen-based hemostatic materials. The sheet-shaped collagen sponge was manufactured by freeze-vacuum drying the aqueous solution of collagen (Col) and heat-denatured collagen (Col’) at a composition ratio of 2/1. The both sides or one side of sponge was treated with ultraviolet (UV) irradiation for 15 minutes to introduce intermolecular crosslinks between collagen molecules. The elution behavior of collagen sponge was investigated by immersing the sponge in water for a predetermined time and then by measuring the weight change. The double-sided UV-irradiated sponge showed very slow elution properties. On the other hand, the single-sided UV-irradiated sponge showed initially fast elution and subsequent very slow elution properties. Such initially fast elution of collagen molecules from the surface without UV-irradiation allows an adhesion of collagen sponge to the wound surface and results in hemostatic effect. In addition, the water absorption and retention properties of sponge were investigated by placing the hydrated sponge on a mesh for a predetermined time and then by measuring the weight change. The double-sided UV-irradiated sponge absorbed 81 times more water than own weight and showed a value of 45 times even after 7 days. The single-sided UV-irradiated sponge absorbed 80 times more water than own weight and showed a value of 39 times even after 7 days. The sponge with high water absorption and retention properties allows a wound healing effect because such sponge can absorb large amounts of blood plasma and exudates containing various cell growth factors. The double-sided UV-irradiated sponge is a good candidate for the wound dressing. On the other hand, the single-sided UV-irradiated sponge is a good candidate for the hemostatic material.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
文摘<span style="line-height:1.5;font-family:Verdana;">This research aims to obtain useful information for development of medical devices such as wound dressing and tissue anti-adhesive product, using a spongy sheet composed of hyaluronic acid (HA) and collagen (Col). The spongy sheets were manufactured by freeze vacuum drying of HA and Col aqueous solution, followed by UV irradiation to introduce intermolecular crosslinks between Col molecules. These spongy sheets are referred to as Sponge-A (ratio of HA/Col = 5/1) and Sponge-B (ratio of HA/Col = 5/5). Both surfaces of Sponge-A and Sponge-B treated with UV irradiation for 15 minutes are referred to as Sponge-A-15 and Sponge-B-15, respectively. The weight change of spongy sheet was determined by immersing a peace of spongy sheet in water at 37°</span><span style="line-height:1.5;font-family:Verdana;">C</span><span style="line-height:1.5;font-family:Verdana;">. The weight of sponge-A-15 collected 1/2, 1, 3, 7 days after immersion in water was 63.5%, 62.1%, 56.6%, 54.4% of the original weight, respectively. The weight of Sponge-B-15 was 78.3%, 76.7%, 79.1%, 71.9% of the original weight, respectively. The weight change of spongy sheet was determined by immersing a peace of spongy sheet in water containing collagenase at 37°</span><span style="line-height:1.5;font-family:Verdana;">C</span><span style="line-height:1.5;font-family:Verdana;">. The weight of Sponge-A-15 collected 6, 8, 10, 12 hours after immersion in water containing collagenase (0.0005</span><span "="" style="line-height:1.5;"> </span><span style="line-height:1.5;font-family:Verdana;">w/v%) was 65.7%, 59.8%, 57.9%, 55.2% of the original weight, respectively. The weight of Sponge-B-15 was 63.5%, 52.1%, 42.0%, 43.2% of the original weight, respectively. This spongy sheet is considered to have the unique structure, where HA molecules are entrapped in an intermolecular cross-linked network structure of Col molecules. When immersed in water containing collagenase, the weight loss of spongy sheet is accelerated by easy extraction of HA molecules from the enzymatic degraded Col network structure. The performance of wound dressing and tissue anti-adhesive product is considered to depend on appropriate ratio of HA and Col, and also on appropriate rate of intermolecular crosslinks between Col molecules. These findings obtained in this study provide useful information for product development such as wound dressing and tissue anti-adhesive product.
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.
文摘This study aims to develop various types of collagen devices for use in oral surgery. The targets are the sheet-shaped sponges to cover mucosal defect wounds (product-1) and gingival defect wounds (product-2) and the cylindrical sponge to fill tooth extraction sockets (product-3). The sheet-shaped sponges were manufactured by freeze-vacuum drying the aqueous solution of collagen (Col) and heat-denatured collagen (Col’) at a composition ratio of 2/1, 1/1 or 1/2. Both surfaces of the sheet-shaped sponge were treated by ultraviolet (UV) irradiation for 5, 10 or 15 minutes to introduce intermolecular crosslinks between collagen molecules. The elution behavior of each collagen sponge was investigated by immersing the sponge in water for a predetermined time and then by measuring the weight change. The collagen sponge composed of Col and Col’ with a composition ratio of 2/1 that was treated by UV irradiation for 15 minutes showed very slow elution properties. This sheet-shaped sponge is the top candidate for product-1. The collagen sponge composed of Col and Col’ with a composition ratio of 2/1 that was treated by UV irradiation for 5 minutes showed slightly fast elution properties. This sheet-shaped sponge is the top candidate for product-2. Next, the cylindrical sponge was manufactured by freeze-vacuum drying the aqueous solution of Col and Col’ at a composition ratio of 2/1. Both sides of the cylindrical sponge were treated by UV irradiation for 15 minutes. This sponge showed initially fast elution properties and subsequent very slow elution properties. This cylindrical sponge is a good candidate for product-3. As a basic design, the sheet-shaped sponge and the cylindrical sponge should be biodegraded and absorbed by the time new tissue formation is completed.
文摘This study aimed to investigate the potential of cultured dermal substitute (CDS) to release angiogenic growth factors when laminated with a membrane containing epidermal growth factor (EGF) as a top dressing. Membranes were prepared by air-drying a solution of hyaluronic acid (HA) and collagen (Col) with or without EGF. Membranes were designed to contain EGF at concentrations of 0, 0.1, 0.2 or 0.5 μg/cm2. CDS was prepared by incorporating fibroblasts into a collagen gel combined with a cross-linked HA spongy matrix, followed by culturing for 5 days. CDS was designed to contain fibroblasts at a density of 2 × 105 (Group I) or 4 × 105 cells/cm2> (Group II). CDS was elevated at the interface between air and culture medium, on the top of which each membrane was placed. This culture system was employed as a wound surface model. Metabolic activity of the fibroblasts in the CDS cultured for 7 days on a wound surface model was measured by MTT assay. The amounts of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) after 7 days of cultivation were measured by using ELISA. Membranes containing EGF ranging from 0.1 to 0.5 μg/cm2> facilitated production of both VEGF and HGF, as compared with control membranes without EGF. However, a membrane containing EGF at a concentration of 0.5 μg/cm2> failed to facilitate fibroblast cytokine production in Group I. These results demonstrated that the EGF-incorporating membrane was able to stimulate fibroblasts in the CDS to synthesize an increased amount of VEGF and HGF in a dose-dependent manner.
文摘This study aims to develop collagen-based hemostatic materials. The sheet-shaped collagen sponge was manufactured by freeze-vacuum drying the aqueous solution of collagen (Col) and heat-denatured collagen (Col’) at a composition ratio of 2/1. The both sides or one side of sponge was treated with ultraviolet (UV) irradiation for 15 minutes to introduce intermolecular crosslinks between collagen molecules. The elution behavior of collagen sponge was investigated by immersing the sponge in water for a predetermined time and then by measuring the weight change. The double-sided UV-irradiated sponge showed very slow elution properties. On the other hand, the single-sided UV-irradiated sponge showed initially fast elution and subsequent very slow elution properties. Such initially fast elution of collagen molecules from the surface without UV-irradiation allows an adhesion of collagen sponge to the wound surface and results in hemostatic effect. In addition, the water absorption and retention properties of sponge were investigated by placing the hydrated sponge on a mesh for a predetermined time and then by measuring the weight change. The double-sided UV-irradiated sponge absorbed 81 times more water than own weight and showed a value of 45 times even after 7 days. The single-sided UV-irradiated sponge absorbed 80 times more water than own weight and showed a value of 39 times even after 7 days. The sponge with high water absorption and retention properties allows a wound healing effect because such sponge can absorb large amounts of blood plasma and exudates containing various cell growth factors. The double-sided UV-irradiated sponge is a good candidate for the wound dressing. On the other hand, the single-sided UV-irradiated sponge is a good candidate for the hemostatic material.
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.
