Papers - HATTORI Hidemi
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PRP&F/P MPs improved survival of dorsal paired pedicle skin flaps in rats Reviewed
Takikawa M., Sumi Y., Ishihara M., Kishimoto S., Nakamura S., Yanagibayashi S., Hattori H., Azuma R., Yamamoto N., Kiyosawa T.
Journal of Surgical Research 170 ( 1 ) e189 - 96 2011.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Surgical Research
Background: Skin flap necrosis is a problem encountered postoperatively. The purpose of this study was to evaluate the effects of platelet-rich plasma containing fragmin/protamine microparticles (PRP&F/P MPs) on viability in a rat dorsal paired pedicle skin (DPPS) flap. Materials and Methods: Two symmetrical adjoining rectangular flaps (8 × 2 cm each) were drawn on the rat dorsum. Two days after PRP&F/P MPs-, PRP-, F/P MPs-, and saline (control)-injections (n = 8 each), flaps were elevated as a random pattern flap without the lateral thoracic, posterior intercostal, and deep circumflex iliac vessels. The flaps were immediately sutured back and the flap survival area was measured 7 d after flap elevation. Results: The flap survival rate in PRP&F/P MPs-injected groups (73.1% ± 4.2%) was significantly higher than those in PRP (64.9% ± 4.0%), F/P MPs (59.4 ± 4.5%), and control (61.2% ± 4.2%) groups. Histologic observation of the flaps showed survived thick granulation tissue and neovascularization in PRP&F/P MPs-injected groups. Conclusions: When PRP&F/P MPs are administered 2 d before the flap elevation, the improved flap survivals are observed. The pre-injection of PRP&F/P MPs may thus represent a promising treatment to prevent skin flap necrosis in reconstructive surgery. © 2011 Elsevier Inc. All rights reserved.
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Hemostasis for severe hemorrhage with photocrosslinkable chitosan hydrogel and calcium alginate Reviewed
Hattori H., Amano Y., Nogami Y., Takase B., Ishihara M.
Annals of Biomedical Engineering 38 ( 12 ) 3724 - 3732 2010.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of Biomedical Engineering
In patients with severe hemorrhage, complications such as shock or death may occur if the patient is not treated appropriately and expeditiously. To create a hemostat kit for severe hemorrhage, ultraviolet light irradiation was applied to photocrosslinkable chitosan hydrogel and calcium alginate. As a hemorrhage model, the femoral arteries and veins of anesthetized rats were cut. Hemodynamics and hematological parameters including red blood cell (RBC) count, hemoglobin concentration, hematocrit, white blood cell (WBC) count, and platelet count, and serum parameters including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured as a marker of hemostasis. In rats for which no procedure was used, death occurred within 30 min. By using the hydrogel hemostat, the survival rate rose to 75% or more. RBC count, hematocrit, hemoglobin, and platelet levels were not significantly changed for 3 days. WBC count increased 1 day after hemostasis. AST and ALT increased 1 day after hemostasis, but it decreased 3 days later. The photocrosslinkable chitosan hydrogel and calcium alginate were biodegraded at 3 and 28 days, respectively, by neutrophils and keratinocyte chemoattractant. © 2010 Biomedical Engineering Society.
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Hydrogel blends of chitin/chitosan, fucoidan and alginate as healing-impaired wound dressings Reviewed
Murakami K., Aoki H., Nakamura S., Nakamura S., Takikawa M., Hanzawa M., Kishimoto S., Hattori H., Tanaka Y., Kiyosawa T., Sato Y., Ishihara M.
Biomaterials 31 ( 1 ) 83 - 90 2010.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Biomaterials
In order to create a moist environment for rapid wound healing, a hydrogel sheet composed of a blended powder of alginate, chitin/chitosan and fucoidan (ACF-HS; 60:20:2:4 w/w) has been developed as a functional wound dressing. ACF-HS gradually absorbed DMEM without any maceration, and fluid absorption became constant within 18 h. On application, ACF-HS was expected to effectively interact with and protect the wound in rats, providing a good moist healing environment with exudates. In addition, the wound dressing has properties such as ease of application and removal and good adherence. Full-thickness skin defects were made on the backs of rats and mitomycin C solution (1 mg/ml in saline) was applied onto the wound for 10 min in order to prepare healing-impaired wounds. After thoroughly washing out the mitomycin C, ACF-HS was applied to the healing-impaired wounds. Although normal rat wound repair was not stimulated by the application of ACF-HS, healing-impaired wound repair was significantly stimulated. Histological examination demonstrated significantly advanced granulation tissue and capillary formation in the healing-impaired wounds treated with ACF-HS on day 7, as compared to those treated with calcium alginate fiber (Kaltostat®; Convatec Ltd., Tokyo, Japan) and those left untreated. © 2009.
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Kishimoto S., Oonuma F., Nakamura S., Hattori H., Nakamura S., Mori Y., Tanaka Y., Harada Y., Tagawa M., Ishihara M.
Journal of Biomedical Materials Research - Part B Applied Biomaterials 92 ( 1 ) 32 - 39 2010.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part B Applied Biomaterials
Fragmin (low-molecular-weight heparin)/protamine microparticles (F/P MPs) immobilize to culture plates, thereby retaining the binding of heparin-binding cytokines such as human stem cell factor (SCF). The purpose of this study was to evaluate the ability of F/P MP-coating to immobilize, stabilize, and enhance SCF-activity. Cell assays showed that SCF and preimmobilized SCF on F/P MP-coated plates significantly stimulated the proliferation of human erythroleukemia cell line TF-1 in a concentration-dependent manner. Heparin and fragmin enhanced SCF-induced proliferation of chlorate-treated TF-1 cells, in which the biosynthesis of endogenous sulfated polysaccharides was blocked, on noncoated plates at a range of concentrations (2-8 μg/mL). However, heparin and fragmin had no effect on SCFinduced proliferation of chlorate-treated TF-1 cells on F/P MP-coated plates. The interaction of SCF with fragmin and F/P MPs prolonged the half-life of SCF bioactivity, and immobilized and protected SCF from inactivation, such as from heat and proteolysis. These results suggest that F/P MP-coated plates protect SCF and enhance its activity, and F/P MP-coating provides an excellent biomaterial to immobilize and retain heparin-binding cytokines, including SCF, in bioactive form for optimal expansion of hematopoietic cells. © 2009 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.b.31486
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Controlled release of FGF-2 using fragmin/protamine microparticles and effect on neovascularization Reviewed
Nakamura S., Kanatani Y., Kishimoto S., Nakamura S., Ohno C., Horio T., Masanori F., Hattori H., Tanaka Y., Kiyosawa T., Maehara T., Ishihara M.
Journal of Biomedical Materials Research - Part A 91 ( 3 ) 814 - 823 2009.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part A
Water-insoluble fragmin/protamine microparticles of about 0.5-1 μm in diameter were prepared by simple mixing of low-molecular-weight heparin (fragmin) with protamine. We investigated the capability of these microparticles to immobilize fibroblast growth factor (FGF)-2, to protect FGF-2 against degradation, to enhance FGF-2 activity, and to facilitate controlled release of FGF-2. FGF-2 bound to the fragmin/protamine microparticles with high affinity (Kd = 2.08 × 10-9 M) and the half-life of FGF-2-activity was prolonged substantially through binding of FGF-2 to the microparticles, by protection of FGF-2 from inactivation by heat and proteolysis. After subcutaneous injection into the back of mice, the fragmin/protamine microparticles underwent biodegradation and disappeared in about 2 weeks. A similar injection of FGF-2-containing microparticles resulted in significant neovascularization and fibrous tissue formation near the injection site after 1 week. These results indicate that controlled release of biologically active FGF-2 occurs through both slow diffusion and biodegradation of the microparticles, with subsequent induction of neovascularization. © 2008 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.a.32265
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Enhancement of the Antifungal Activity of Silver Ion Agents by the Addition of Plant Extracts Reviewed
37 ( 11 ) 813 - 9 2009.11
Language：Japanese Publishing type：Research paper (scientific journal)
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Kishimoto S., Hattori H., Nakamura S., Amano Y., Kanatani Y., Tanaka Y., Mori Y., Harada Y., Tagawa M., Ishihara M.
Tissue engineering. Part C, Methods 15 ( 3 ) 523 - 527 2009.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Tissue engineering. Part C, Methods
Fragmin/protamine microparticles (F/P MPs) can be stably coated onto plastic surfaces. A capability of F/P MP-coated plates was investigated to immobilize fibroblast growth factor (FGF)-2 as a substratum to expand human bone marrow-derived mesenchymal stem cells (BMMSCs). FGF-2 molecules in low (2%) human serum (HS) medium were immobilized onto F/P MP-coated plates, and the FGF-2 was gradually released into the medium with a half-releasing time of 4-5 days. BMMSCs adhered well to the F/P MP-coated plates, and grew at a doubling time of about 28 h in low (2%) HS medium with FGF-2 (5 ng/mL), while the cells grew at a doubling time of about 30 and 38 h in high (10%) HS medium and in low (2%) HS medium with FGF-2, respectively, without F/P MP coating. The expanded BMMSCs on the F/P MP-coated plates in low (2%) HS medium with FGF-2 maintained their multilineage potential for differentiation into adipocytes and osteoblasts.
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Usefulness of automatic QT dispersion measurement for detecting exercise-induced myocardial ischemia Reviewed
Takase B., Masaki N., Hattori H., Ishihara M., Kurita A.
Anadolu Kardiyoloji Dergisi 9 ( 3 ) 189 - 195 2009.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Anadolu Kardiyoloji Dergisi
Objective: The electrocardiographic index of QT dispersion (QTd) is related to the occurrence of arrhythmia. In patients with suspected or known coronary artery disease, QTd may be affected by exercise. We investigated whether QTd that is automatically calculated by a newly developed computer system could be used as a marker of exercise-induced myocardial ischemia. Methods: The design of this study was prospective and observational. Eighty-three consecutive patients were enrolled in this study. Their QTd was measured at rest and after 3 min of exercise during exercise-stress Thallium-201 scintigraphy and compared with conventional ST-segment changes. The patients were classified into 4 groups (normal group, redistribution group, fixed defect group, redistribution with fixed defect group) based on the result of single photon emission computed tomography. As statistical analysis, one-way ANOVA with post-hoc Scheffe's method, receiver-operating characteristics (ROC) and multiple logistic regression analysis were performed. Results: At rest, QTd was significantly greater (p<0.05) in the fixed defect group (52±21 ms) and the redistribution with fixed defect group (53±20 ms) than in the normal group (32±14 ms) and the redistribution group (31±16 ms). However, QTd tended to increase after exercise in the redistribution group, while QTd tended to decrease in the normal group, the fixed defect group, and the redistribution with fixed defect group (QTd after exercise, normal group, 28±17 ms, redistribution group, 35±19 ms, fixed defect group, 43±25 ms, redistribution with fixed defect group, 49±27 ms). Exercise significantly increased QTcd (RR interval-corrected QT dispersion) in the redistribution group. The best cut-off values of QTd and QTcd obtained from ROC curves for exercise-induced myocardial ischemia were 41.6 ms and 40.4 ms, respectively (Qtd - AUC 0.68, 95%CI 0.53- 0.83 and QTcd - AUC 0.67, 95%CI 0.55-0.80). Using these values as cut-off ones, QTd, QTcd, and conventional ST-segment change had comparable sensitivities and specificities for detecting exercise-induced myocardial ischemia (sensitivity - 60%, 58% and 49%, respectively; specificity - 78%, 80% and 83%, respectively). In addition, multiple logistic regression analysis showed that QTd (OR=2.01, 95%CI 1.15-4.10, p<0.05), QTcd (OR=2.12, 95% CI 1.02-4.30, p<0.05) and ST-segment change (OR=1.89, 95%CI 1.03-3.40, p<0.05), were the significantly associated with exercise-induced myocardial ischemia. Conclusion: QT dispersion and/or QTcd after exercise could be a useful marker for exercise-induced myocardial ischemia in routine clinical practice. © Copyright 2009 by AVES Yayincilik Ltd.
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Periodic recurrence of wide QRS tachycardia in myocardial infarction and vasospasm: utility of heart rate variability to assess autonomic nervous system activity on vasospasm-induced lethal arrhythmia. Reviewed
Takase B, Kimura K, Hamabe A, Uehata A, Hidemi H, Ishihara M, Kurita A
Anadolu kardiyoloji dergisi 9 ( 4 ) 345 - 7 2009.8
Language：English Publishing type：Research paper (scientific journal)
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Kishimoto S., Nakamura S., Nakamura S., Kanatani Y., Hattori H., Tanaka Y., Harada Y., Tagawa M., Mori Y., Maehara T., Ishihara M.
Artificial Organs 33 ( 6 ) 431 - 438 2009.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Artificial Organs
Fragmin/protamine microparticles (F/P MPs) have been shown to bind to culture plates, thereby retaining heparin-binding cytokines. Most protocols for in vitro cultures of human microvascular endothelial cells (hMVECs), human dermal fibroblast cells (hDFCs), and hematopoietic cell line (TF-1) include high fetal bovine serum (FBS) (10%) medium as a nutritional supplement. Growth rates of those cells on the F/P MP-coated plates were higher in low FBS (1%) medium containing fibroblast growth factor (FGF)-2 (for hMVECs and hDFCs) and interleukin (IL)-3/granulocyte-macrophage colony-stimulating factor (for TF-1 cells) than without coating. The cytokines in low FBS medium were shown to be immobilized on the F/P MP-coated plate and released into the culture medium with a half releasing time of 4-5 days. Furthermore, those cells grew well on each cytokine-preimmobilized F/P MP-coated plate in low FBS medium. Thus, the F/P MP-coated matrix with adequate heparin-binding cytokines may provide biomaterials for controlling cellular growth and differentiation. © 2009, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
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Hattori H., Higuchi K., Nogami Y., Amano Y., Ishihara M., Takase B.
Circulation: Cardiovascular Imaging 2 ( 3 ) 277 - 278 2009.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Circulation: Cardiovascular Imaging
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Human stem cell factor (SCF) is a heparin-binding cytokine Reviewed
Kishimoto S., Nakamura S., Hattori H., Nakamura S., Oonuma F., Kanatani Y., Tanaka Y., Mori Y., Harada Y., Tagawa M., Ishihara M.
Journal of Biochemistry 145 ( 3 ) 275 - 278 2009.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biochemistry
Binding affinities of chemically modified heparins for human stem cell factor (SCF) were examined using fragmin/protamine microparticles (F/P MPs) and an enzyme-linked immunosorbent assay (ELISA). The binding of SCF to F/P MP-coated plates was inhibited with high concentrations of heparin and fragmin, but not others. The binding of SCF was also inhibited with 0.55 M or higher concentrations of NaCl in the medium. These results suggested that a high content of all three sulfate groups in repeating disaccharide units is required for interaction with SCF. Furthermore, pre-immobilized SCF on F/P MP-coated plates significantly stimulated proliferation of a human erythroleukemia cell line. © The Authors 2008. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
DOI： 10.1093/jb/mvn169
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Cytokine-immobilized microparticle-coated plates for culturing hematopoietic progenitor cells Reviewed
Kishimoto S., Nakamura S., Nakamura S., Hattori H., Oonuma F., Kanatani Y., Tanaka Y., Harada Y., Tagawa M., Maehara T., Ishihara M.
Journal of Controlled Release 133 ( 3 ) 185 - 190 2009.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Controlled Release
The purpose of this study was to provide a culture method for an effective expansion of human CD 34 positive hematopoietic progenitor cells (CD 34 (+) HCs) utilizing low molecular weight heparin/protamine microparticles (LH/P MPs) which can be stably coated onto plastic surfaces and cytokines. CD 34 (+) HCs optimally proliferated on LH/P MP-coated plates in the presence of stem cell factor (SCF; 5 ng/ml), thrombopoietin (Tpo; 10 ng/ml), and Flt-3 ligand (Flt-3; 10 ng/ml) in hematopoietic progenitor growth medium (HPGM). After 6 days, the total cells expanded 16.5-fold. Those cytokines were shown to be partially immobilized on the LH/P MP-coated plates, and the immobilized cytokines were gradually released into the medium with half releasing time of 3-4 days. Since flow cytometry analyses revealed that 90% of initial cells and 44.5% of expanded cells were CD 34 positive, CD 34 (+) HCs were estimated to have increased 8.0-fold after 6 days, and to have increased to over 31.9-fold after 12 days. In contrast, cultured CD 34 (+) HCs on non-coated tissue culture plates increased only 2.9-fold in the identical medium after 6 days, and only 5.2-fold after 12 days. © 2008 Elsevier B.V. All rights reserved.
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Ishizuka T., Ishihara M., Aiko S., Nogami Y., Nakamura S., Kanatani Y., Kishimoto S., Hattori H., Horio T., Tanaka Y., Maehara T.
Endoscopy 41 ( 1 ) 25 - 28 2009.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Endoscopy
Background and study aims: Saline as an injection solution for endoscopic resection techniques has several disadvantages such as a short-lasting effect leading to a potentially higher risk of bleeding and perforation. The new substance of photocrosslinkable chitosan hydrogel in a DMEM/F12 medium (PCH) can be converted into an insoluble hydrogel by ultraviolet irradiation for 30 s, and was evaluated in two sets of animal experiments. Methods: 18 pigs were used in the two parts of the study. First, mucosal resections were done with either PCH or hypertonic saline; the effects of both agents on wound healing were examined endoscopically and histologically. Second, in vivo degradation of PCH was examined using six pig stomachs. Result: PCH injection led to a longer-lasting elevation with clearer margins, compared with hypertonic saline, thus enabling precise endoscopic submucosal dissection (ESD) along the margins of the elevated mucosa. The endoscopic appearance after ESD was similar in both groups. PCH biodegradation was completed within 8 weeks according to endoscopic and histologic analyses. Conclusion: PCH is a promising agent for submucosal injection prior to various techniques of endoresection. It should be evaluated in clinical trials after biocompatibility testing for PCH is completed. © Georg Thieme Verlag KG Stuttgart.
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FGF-2含有フラグミンプロタミンマイクロキャリア(F/P MPs)による虚血改善効果の検討. Reviewed
片桐彰男, 橋谷華世, 中村伸吾, 服部秀美, 岸本聡子, 前原正明, 石原雅之.
防衛衛生 56 ( 1 ) 17 - 24 2009.1
Language：Japanese Publishing type：Research paper (scientific journal)
塩基性線維芽細胞増殖因子(fibroblast growth factor-2:FGF-2)には、例えば、血管新生作用や創傷治癒作用などの様々な重要な生理作用があることが知られている。FGF-2は、立体構造の不安定さなどから生体内における活性半減期が非常に短いが、ヘパリンやヘパラン硫酸といったヘパリノイドと相互作用することにより、構造を安定化したり受容体との結合を効率よく進めたりする。我々はこれまでに、低分子化ヘパリンであるフラグミンとその中和剤であるプロタミンを混合することで容易に作製できるフラグミンプロタミンマイクロキャリア(F/P MPs;fragmin/protamine micro particles)についての報告を行ってきた。このF/P MPsは、FGF-2を様々な不活化要因から保護して活性を維持延長させることができる。また、FGF-2含有F/P MPsをマウスの背部皮下へ注入すると、当該部位において血管新生が促進される。そこで本研究では、後肢虚血モデル動物を作製し、ここにFGF-2含有F/P MPsを投与することで虚血状態が改善し治療効果が得られるかどうかの基礎検討を行った。その結果、FGF-2含有F/P MPsを投与した後肢虚血モデル動物では壊死が防がれ、未処置群と比べて酸素飽和度も大幅な改善がみられた。したがって、FGF-2含有F/P MPsは虚血性疾患に対する治療に有用なマテリアルになると考えられた。
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Tsuda Y., Ishihara M., Amako M., Arino H., Hattori H., Kanatani Y., Yura H., Nemoto K.
Artificial Organs 33 ( 1 ) 74 - 77 2009.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Artificial Organs
UV light irradiation to a photocrosslinkable chitosan (Az-CH-LA) resulted in an insoluble and flexible hydrogel within 30 s. The purpose of this study was to evaluate the ability of the photocrosslinkable chitosan to inhibit bone formation in the bone defects. A 5-mm-diameter defect was made in the rat calvarium, and then photocrosslinkable chitosan was implanted and irradiated with UV for 30 s. Furthermore, a 2-mm defect was made in the fibula of a rat hind leg, and then photocrosslinkable chitosan was implanted and irradiated with UV. Bone formations in the rat skull and fibula defects with photocrosslinkable chitosan hydrogel were significantly prevented for 8 weeks. Thus, the chitosan hydrogel has an inhibitory effect on bone formation. © 2009, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
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Hattori H., Nogami Y., Tanaka T., Amano Y., Fukuda K., Kishimoto S., Kanatani Y., Nakamura S., Takase B., Ishihara M.
Journal of Biomedical Materials Research - Part B Applied Biomaterials 87 ( 1 ) 229 - 236 2008.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part B Applied Biomaterials
Adipose tissue contains a population of cells that have extensive self-renewal capacity and the ability to differentiate along multiple lineages. In addition, adipose tissue-derived stromal cells (ATSCs) are able to differentiate into various cell types that may be useful for autologous cell transplantation for defects of bone, cartilage, adipose, and tendon, etc. Most protocols for in vitro cultures of ATSCs include fetal bovine serum (FBS) as a nutritional supplement. However, in some cell cultures, it involves multiple doses of FBS, which raises a concern over possible infections as well as immunological reactions that are caused by medium-derived FBS proteins, sialic acid, etc. In this study, we were able to expand mouse ATSCs using low mouse serum media containing collagen type I, heparin-carrying polystyrene, and fibroblast growth factor (FGF)-2. These expanded mouse ATSCs maintained their multilineage potential for differentiation into adipocytes, osteoblasts, and chondrocytes. Therefore, this method, which uses autologous cells and low serum media, may be able to be utilized for clinical cell therapies. © 2008 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.b.31101
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虚血性心疾患の予後予測における上腕動脈内皮機能の役割に関する検討. Invited
高瀬凡平, 上畑昭美, 木村一生, 服部秀美, 石原雅之, 栗田明.
血圧 15 ( 9 ) 762 - 5 2008.9
Language：Japanese Publishing type：Research paper (scientific journal)
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Nakamura S., Nambu M., Ishizuka T., Hattori H., Kanatani Y., Takase B., Kishimoto S., Amano Y., Aoki H., Kiyosawa T., Ishihara M., Maehara T.
Journal of Biomedical Materials Research - Part A 85 ( 3 ) 619 - 627 2008.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part A
We produced a chitosan/fucoidan micro complex-hydrogel as a carrier for controlled release of heparin binding growth factors such as fibroblast growth factor (FGF)-2. Material consisting of a soluble chitosan (CH-LA) mixed with fucoidan yielded a water-insoluble and injectable hydrogel with filamentous particles. In this study, we examined the ability of the chitosan/fucoidan complex-hydrogel to immobilize FGF-2 and to protect its activity, as well as the controlled release of FGF-2 molecules. The chitosan/fucoidan complex-hydrogel has high affinity for FGF-2 (Xd = 5.4 × 10-9 M). The interaction of FGF-2 with chitosan/fucoidan complex-hydrogel substantially prolonged the biological half-life time of FGF-2. It also protected FGF-2 from inactivation, for example by heat and proteolysis, and enhance FGF-2 activity. When FGF-2-containing complex-hydrogel was subcutaneously injected into the back of mice, significant neovascularization and fibrous tissue formation were induced near the site of injection at 1 week, and the complex-hydrogel was biodegraded and disappeared by 4 weeks. These findings indicate that controlled release of biologically active FGF-2 molecules is caused by both slow diffusion and biodegradation of the complex-hydrogel, and that subsequent induction of vascularization occurs. FGF-2-containing chitosan/fucoidan micro complex-hydrogel is thus useful and convenient for treatment of ischemic disease. © 2007 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.a.31563
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フラグミン/プロタミンマイクロキャリアによるFGF-2の活性保護効果と血管新生効果. Reviewed
大野千寿子, 中村伸吾, 南部正樹, 野上弥志郎, 岸本聡子, 天野嘉子, 服部秀美, 高瀬凡平, 前原正明, 石原雅之.
防衛衛生 54 ( 10 ) 259 - 67 2007.10
Language：Japanese Publishing type：Research paper (scientific journal)