研究者詳細 - 松本　卓也

論文 - 松本　卓也

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Regulation of the protein-loading capacity of hydroxyapatite by mercaptosuccinic acid modification

Shiho Ishihara, Takuya Matsumoto, Takamasa Onoki, Mohammad Hafiz Uddin, Taiji Sohmura, Atsushi Nakahira

ACTA BIOMATERIALIA 6 ( 3 ) 830 - 835 2010年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI LTD

Loading and releasing protein in a controllable way is extremely important for the protein vehicles used in bone tissue engineering. To obtain a suitable carrier material for basic proteins, such as BMP or bFGF, hydroxyapatite particles containing mercaptosuccinic acid (mercaptosuccinic acid (Met), (Mer-HAp)) were synthesized Physicochemical evaluation of Mer-HAp suggested that Mer was contained in HAp particles: it either simply adsorbed onto HAp crystals or was trapped among the HAp crystals. A protein adsorption Study using basic and acidic model proteins indicated that the synthesized Mer-HAp had selective loading properties of the basic protein. The loaded protein was gradually released from Mer-HAp in phosphate buffered saline. The protein release rate was different in each Mer-HAp synthesized with a different concentration of Mer. In addition, the protein release from Mer-HAp showed a similar profile with the Ca dissolution in different pH solutions, indicating that the Mer-HAp dissolution was concerned with the protein release from Mer-HAp Thus, Mer-HAp is a useful candidate for the basic protein carrier because it has properties which enable the loading and releasing of protein in a controllable way. (C) 2009 Acta Materialia Inc Published by Elsevier Ltd. All rights reserved

DOI： 10.1016/j.actbio.2009.10.019

Synthesis of hydroxyapatite containing manganese and its evaluation of biocompatibility.

Fujitani W, Hamada Y, Kawaguchi N, Mori S, Daito K, Uchinaka A, Matsumoto T, Kojima Y, Daito M, Nakano T, Matsuura N

Nano Biomed. 2 ( 1 ) 37 - 46 2010年

記述言語：英語出版者・発行元：ナノ・バイオメディカル学会

Biomaterials made using hydroxyapatite (HAp) and calcium phosphates, which are inorganic components of hard tissues, have been developed to fill bone defects caused by various diseases. A biomaterial of HAp containing collagen, an organic component of bone, has also been developed. However, the physical and biological functions of these bone biomaterials remain inadequate.<br>Focusing on Zinc(Zn) and Manganese(Mn) ions out of the divalent cations involved in the activity of integrins, which are molecules existing in cell membranes, we synthesized three kinds of inorganic biomaterials—pure HAp, Zn-containing HAp (Zn-HAp), and Mn-containing HAp (Mn-HAp)—by a wet process. These three kinds of HAp powders were formed into pellets of 6mm diameter and 1mm thickness and their bio-adaptability was investigated.<br>In vitro experiments using osteoblast-like cells (MC3T3E1) demonstrated that Mn-HAp showed higher cell adhesion potential than pure HAp, indicating that Mn addition improves bioresponses. This may be because Mn ions eluted from Mn-HAp pellets activated integrins, which are closely related to the cell adhesion potential of MC3T3E1 cells to the surface of the pellets.

DOI： 10.11344/nano.2.37.

In vitro engineering of transitional tissue by patterning and functional control of cells in fibrin gel 査読

Jun-Ichi Sasaki, Takuya Matsumoto, Hiroshi Egusa, Takayoshi Nakano, Takuya Ishimoto, Taiji Sohmura, Hirofumi Yatani

SOFT MATTER 6 ( 8 ) 1662 - 1667 2010年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ROYAL SOC CHEMISTRY

Tendon insertions show specific three-dimensional (3D) cell and matrix configurations. To fabricate this transitional tissue in vitro, the development of a cell manipulation technique that can control cell and matrix patterning in the 3D construct is crucial. Bone marrow-derived stromal cells and osteoblasts were respectively cultured in fibrin gel using a custom-made device that can apply uniaxial continuous tensile strain to the gel at different strain rates. Cells in the strained fibrin gel showed a specific orientation, which was parallel to the strain direction, because of the structural change of fibrin fibres within the strained gel. The direction of cell proliferation in the strained gel was also restricted to the same direction. Subsequently, linearly aligned cell sets, similar to the cell patterning of tendon tissue, were obtained in this culture system. Notably, linearly aligned extracellular matrix and mineral patterning, which are crucial for the fabrication of tendon insertions, were also confirmed in the strained fibrin gel. A cell proliferation assay indicated that the strained gel with a higher strain rate enhanced cell proliferation in the gel. In contrast, a Real-Time PCR study indicated that the strained gel with a lower strain rate enhanced cell differentiation in the gel. Thus, our new cell culture system enabled us to fabricate a 3D construct containing patterned cells and matrices in a controllable manner. This would be an effective tool for reproducing tendon insertions in vitro.

DOI： 10.1039/b922418a

A small-molecule approach to bone regenerative medicine in dentistry

Hiroshi Egusa, Makio Saeki, Masanori Doi, Sho Fukuyasu, Takuya Matsumoto, Yoshinori Kamisaki, Hirofumi Yatani

Journal of Oral Biosciences 52 ( 2 ) 107 - 118 2010年

記述言語：英語出版者・発行元：Japanese Association for Oral Biology

The resorption of alveolar bone in periodontitis and/or following toothextraction results in a significant problem in an individual's oral health-related quality of life. Strategies employing growth factor proteins and/orstem cell-based therapy have been successfully used to regenerate alveolarbone augmentationregeneration/however, cost-effectiveness issues illustratethe need for developing alternative strategies. One promising approach is the development of conventional chemical and biological therapeuticsto strongly stimulate endogenous cells to regenerate. Small-molecule compounds can have a variety of biological functions, serving as cell signaling molecules, as tools in molecular biology, and as drugs in medicine. Therefore, the discovery of natural and novel small-molecule synthetic regulators of differentiation and maturation of osteoblasts and/or osteoclasts would acceleratethe development of bone regenerative medicine. Recently,"chemical biology" has started to play an increasingly important role in both drug discovery and elucidating the mechanism of biological phenomena. This review first addresses the current needs and strategies for alveolar bone regeneration, followed by the potential small molecules associated with bone regeneration, with a concluding section on chemical biology-based high throughput screening approaches for identifying small molecules targeting osteoblast/osteoclast differentiation.

DOI： 10.2330/joralbiosci.52.107

Organic/inorganic composite material synthesized with osteoblastic cells 査読

T.Matsumoto, A.Mizuno, M.Okazaki, T.Nakano, T.Sohmura

2009年12月

Mass Fabrication of Small Cell Spheroids by Using Micro-patterned Tissue Culture Plate

Akinari Iwasaki, Takuya Matsumoto, Go Tazaki, Hitoshi Tsuruta, Hiroshi Egusa, Hiroyuki Miyajima, Taiji Sohmura

ADVANCED ENGINEERING MATERIALS 11 ( 10 ) 801 - 804 2009年10月

Enhanced bone regeneration via multimodal actions of synthetic peptide SVVYGLR on osteoprogenitors and osteoclasts

Hiroshi Egusa, Yoshitoshi Kaneda, Yoshihiro Akashi, Yoshinosuke Hamada, Takuya Matsumoto, Makio Saeki, Devang K. Thakor, Yasuhiko Tabata, Nariaki Matsuura, Hirofumi Yatani

BIOMATERIALS 30 ( 27 ) 4676 - 4686 2009年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI LTD

Recently, the binding sequence Ser-Val-Val-Tyr-Gly-Leu-Arg (SVVYGLR) was found adjacent to the RGD sequence in osteopontin, suggesting involvement in osteo-immune cross-talk. The aim of this study was to investigate bioactive functions of a synthetic SVVYGLR peptide in osteoprogenitor cells and osteoclasts, and to examine potential applications in bone regeneration. The SVVYGLR peptide significantly enhanced the adhesion and proliferation of several human mesenchymal cells including bone marrow-derived mesenchymal stem cells, and alpha v beta 3 integrin was involved in cell attachment to the peptide. Additionally, the peptide reduced the number of TRAP-positive multinucleated cells during osteoclastogenesis of RAW264.7 cells and normal murine pre-osteoclasts, and also suppressed NFAT activity and expression of osteoclastogenesis-related mRNAs. When standardized bone defects in rat calvariae were filled with a collagen sponge containing the peptide or PBS (control), the number of TRAP-positive osteoclasts in the grafted sites after 3 weeks was significantly lower in the peptide group. By the 5th week, significantly enhanced resorption of the grafted collagen sponge and new bone formation was observed within and surrounding the sponge in the peptide group. These data suggest that SVVYGLR is an effective bioactive peptide for bone tissue regeneration that promotes attachment and proliferation of osteogenic cells while also suppressing osteoclastogenesis. (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.biomaterials.2009.05.032

New concept bioceramics composed of octacalcium phosphate (OCP) and dicarboxylic acid-intercalated OCP via hydrothermal hot-pressing

Shiho Ishihara, Takuya Matsumoto, Takamasa Onoki, Taiji Sohmura, Atsushi Nakahira

MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS 29 ( 6 ) 1885 - 1888 2009年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

Octacalcium phosphate (OCP) and adipic acid-intercalated complexed OCP (Adi-OCP) were synthesized. Moreover, we made ceramic bodies out of them through a hydrothermal hot-pressing (HHP) method. Characteristic features of both the powder and ceramics were investigated by the X-ray diffraction method (XRD). Surface morphology of the ceramics was observed by scanning electron microscopy (SEM). Density, compressive strength and pore size distribution of the ceramics were measured. Crystalline structure of the newly developed OCP ceramics had no phase transformation from the starting materials. Moreover, the newly developed OCP ceramics had good mechanical properties only through the HHP treatment with a temperature as low as 110 degrees C. In order to evaluate bioactivity, the ceramics were immersed in simulating body fluid (SBF). It was predicted that OCP and Adi-OCP had better bioactivity than that of conventional HAp ceramics. (C) 2009 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.msec.2009.02.023

Clinical Evaluation of the Efficacy of Removing Microorganisms to Disinfect Patient-Derived Dental Impressions 査読

Hiroshi Egusa, Takao Watamoto, Takuya Matsumoto, Keiko Abe, Munemasa Kobayashi, Yoshihiro Akashi, Hirofumi Yatani

INTERNATIONAL JOURNAL OF PROSTHODONTICS 21 ( 6 ) 531 - 538 2008年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：QUINTESSENCE PUBLISHING CO INC

Purpose: Disinfection of dental impressions is an indispensable procedure for the control of cross-contaminatior however, there is limited information on the efficacy of disinfection under clinical conditions. The objective of this study was to clinically evaluate the disinfection efficacy of commercially available agents in removing oral pathogens from patient-derived impressions. Materials and Methods: Impressions from 54 patients were divided into groups and either left undisinfected or underwent I of 5 disinfection treatments: ( 1) 2% glutaraldehyde (GA), (2) 1% sodium hypochlorite (SH), (3) 0.25% benzalkonium chloride (BC), (4) 1 ppm ozonated water (OW), or (5) the Hygojet/MD520 system (HJ). An impression culture technique using a brain heart infusion agar medium was used to visualize the microbial contamination on the surface of the impression cultures. The persistent presence of oral pathogens on the impression cultures was examined using selective isolation agar plates. Results: The isolation frequencies of streptococci, staphylococci, Candida, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa species from undisinfected impressions were 100%, 55.6%, 25.9%. 25.9% and 5.6%. respectively. Disinfection with HJ and BC removed the microorganisms with the greatest efficacy, followed by GA, SH, and OW. Potential bacterial contamination could be detected even after disinfection had been performed. Combined use of BC plus GA or SH removed oral pathogens almost completely from dental impressions, Conclusions: This investigation showed that potential contaminants are still present, even after general disinfection procedures. Therefore. either HJ or the combined use of BC with GA or SH is recommended for clinical and laboratory use. Int J Prosthodont 200821,531-538.

Three-dimensional cell and tissue patterning in a strained fibrin gel system.

Matsumoto T, Sasaki J, Alsberg E, Egusa H, Yatani H, Sohmura T

PLoS ONE. 2 e1211 2008年

Synthetic osteopontin-derived peptide SVVYGLR can induce neovascularization in artificial bone marrow scaffold bioniaterials 査読

Yoshinosuke Hamada, Hiroshi Egusa, Yoshitoshi Kaneda, Isao Hirata, Naomasa Kawaguchi, Takafumi Hirao, Takuya Matsumoto, Makiko Yao, Kiyoshi Daito, Mayuka Suzuki

DENTAL MATERIALS JOURNAL 26 ( 4 ) 487 - 492 2007年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPANESE SOC DENTAL MATERIALS DEVICES

We have previously reported that an osteopontin -derived SVVYGLR peptide exhibited potent angiogenic activity in vitro and in vivo. In the present study, the focus points were on the in vitro effect of SVVYGLR on bone marrow stromal cell proliferation, as well as its in vivo effect on bone tissue formation when grafts made Of CO3 Ap-collagen sponge-as a scaffold biornaterial containing the SVVYGLR motif - were implanted. SVVYGLR peptide promoted bone marrow stromal cell proliferation. When a CO,Ap-collagen sponge containing SVVYGLR peptide was implanted as a graft into a tissue defect created in rat tibia, the migration of numerous vascular endothelial cells - as well as prominent angiogenesis - inside the graft could be detected after one week. These results thus suggested that our scaffold biomaterials including the peptide could be useful for bone tissue regeneration.

Synthetic osteopontin-derived peptide SVVYGLR can induce neovascularization in artificial bone marrow scaffold bioniaterials 査読

Yoshinosuke Hamada, Hiroshi Egusa, Yoshitoshi Kaneda, Isao Hirata, Naomasa Kawaguchi, Takafumi Hirao, Takuya Matsumoto, Makiko Yao, Kiyoshi Daito, Mayuka Suzuki

DENTAL MATERIALS JOURNAL 26 ( 4 ) 487 - 492 2007年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPANESE SOC DENTAL MATERIALS DEVICES

We have previously reported that an osteopontin -derived SVVYGLR peptide exhibited potent angiogenic activity in vitro and in vivo. In the present study, the focus points were on the in vitro effect of SVVYGLR on bone marrow stromal cell proliferation, as well as its in vivo effect on bone tissue formation when grafts made Of CO3 Ap-collagen sponge-as a scaffold biornaterial containing the SVVYGLR motif - were implanted. SVVYGLR peptide promoted bone marrow stromal cell proliferation. When a CO,Ap-collagen sponge containing SVVYGLR peptide was implanted as a graft into a tissue defect created in rat tibia, the migration of numerous vascular endothelial cells - as well as prominent angiogenesis - inside the graft could be detected after one week. These results thus suggested that our scaffold biomaterials including the peptide could be useful for bone tissue regeneration.

DOI： 10.4012/dmj.26.487

Different behavior of implanted hydroxyapatite depending on morphology, size and crystallinity

Takuya Matsumoto, Ken-ichi Tamine, Ryosuke Kagawa, Yoshinosuke Hamada, Masayuki Okazaki, Junzo Takahashi

JOURNAL OF THE CERAMIC SOCIETY OF JAPAN 114 ( 1333 ) 760 - 762 2006年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CERAMIC SOC JAPAN-NIPPON SERAMIKKUSU KYOKAI

Hydroxyapatite (HAp) materials with different morphology, size and crystallinity were prepared and were implanted into a male rat tibia. Each of the HAp materials showed a high biocompatiblity and osteoconductivity. The morphology and size of the implanted HAp affected the intrusion of bone marrow derived cells among HAp materials, and this cell intrusion was important for regulating the newly formed bone mass. High crystalline sintered HAp was stable and remained in its initial shape for long periods. However, low crystalline HAp was absorbed and disappeared during bone remodeling. This study indicates that choosing suitable HAp materials in morphology, size and crystallinity is important for a treatment plan (e.g. reconstruction or regeneration; large region or small region etc.) and for achieving a desired prognosis.

Different behavior of implanted hydroxyapatite depending on morphology, size and crystallinity 査読

Takuya Matsumoto, Ken-ichi Tamine, Ryosuke Kagawa, Yoshinosuke Hamada, Masayuki Okazaki, Junzo Takahashi

JOURNAL OF THE CERAMIC SOCIETY OF JAPAN 114 ( 1333 ) 760 - 762 2006年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CERAMIC SOC JAPAN-NIPPON SERAMIKKUSU KYOKAI

Hydroxyapatite (HAp) materials with different morphology, size and crystallinity were prepared and were implanted into a male rat tibia. Each of the HAp materials showed a high biocompatiblity and osteoconductivity. The morphology and size of the implanted HAp affected the intrusion of bone marrow derived cells among HAp materials, and this cell intrusion was important for regulating the newly formed bone mass. High crystalline sintered HAp was stable and remained in its initial shape for long periods. However, low crystalline HAp was absorbed and disappeared during bone remodeling. This study indicates that choosing suitable HAp materials in morphology, size and crystallinity is important for a treatment plan (e.g. reconstruction or regeneration; large region or small region etc.) and for achieving a desired prognosis.

DOI： 10.2109/jcersj.114.760

Role of acidic amino acid for regulating hydroxyapatite crystal growth 査読

Takuya Matsumoto, Masayuki Okazaki, Masahiro Inoue, Jun-Ichi Sasaki, Yoshinosuke Hamada, Junzo Takahashi

DENTAL MATERIALS JOURNAL 25 ( 2 ) 360 - 364 2006年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPANESE SOC DENTAL MATERIALS DEVICES

Non-collagenous proteins in hard tissue matrix are thought to play a pivotal role in regulating the crystal growth of hydroxyapatite (HAp). As most non-collagenous proteins are acidic proteins containing acidic amino acid-rich sequences, we examined the growth of HAp crystals from HAp seed crystals in the presence/absence of acidic amino acid. New HAp formation generally started from the P-surface of HAp. However, in the presence of acidic amino acid, new HAp formation was observed on both P-surface and C-surface of HAp seed crystals. Furthermore, newly formed HAp showed specific orientation along the long-axis direction of HAp seed crystals. In terms of crystallinity, HAp formed in the presence of acidic amino acid showed low crystallinity. These results suggested that, in biomineralization, the adsorbed or free state of acidic amino acid would influence crystal formation and orientation as follows: 1) If free in solution, acidic amino acid would inhibit HAp crystal growth; 2) If adsorbed or immobilized on matrix, acidic amino acid would become HAp nucleation site and regulate the orientation of HAp crystals.

DOI： 10.4012/dmj.25.360

Cell instructive polymers 査読

Takuya Matsumoto, David J. Mooney

TISSUE ENGINEERING I: SCAFFOLD SYSTEMS FOR TISSUE ENGINEERING 102 113 - 137 2006年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER-VERLAG BERLIN

Polymeric materials used in tissue engineering were initially used solely as delivery vehicles for transplanting cells. However, these materials are currently designed to actively regulate the resultant tissue structure and function. This control is achieved through spatial and temporal regulation of various cues (e.g., adhesion ligands, growth factors) provided to interacting cells from the material. These polymeric materials that control cell function and tissue formation are termed cell instructive polymers, and recent trends in their design are outlined in this chapter.

DOI： 10.1007/b137207

Different behavior of implanted hydroxyapatite depending on morphology, size and crystallinity 査読

Takuya Matsumoto, Ken-Ichi Tamine, Ryosuke Kagawa, Yoshinosuke Hamada, Masayuki Okazaki, Junzo Takahashi

Journal of the Ceramic Society of Japan 114 ( 1333 ) 760 - 762 2006年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Ceramic Society of Japan

Hydroxyapatite (HAp) materials with different morphology, size and crystallinity were prepared and were implanted into a male rat tibia. Each of the HAp materials showed a high biocompatiblity and osteoconductivity. The morphology and size of the implanted HAp affected the intrusion of bone marrow derived cells among HAp materials, and this cell intrusion was important for regulating the newly formed bone mass. High crystalline sintered HAp was stable and remained in its initial shape for long periods. However, low crystalline HAp was absorbed and disappeared during bone remodeling. This study indicates that choosing suitable HAp materials in morphology, size and crystallinity is important for a treatment plan (e.g. reconstruction or regeneration
large region or small region etc.) and for achieving a desired prognosis.

DOI： 10.2109/jcersj.114.760

Advantages of TOF-SIMS analysis of hydroxyapatite and fluorapatite in comparison with XRD, HR-TEM and FT-IR

M Okazaki, Hirata, I, T Matsumoto, J Takahashi

DENTAL MATERIALS JOURNAL 24 ( 4 ) 508 - 514 2005年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPANESE SOC DENTAL MATERIALS DEVICES

The chemical analysis of hydroxyapatite and fluorapatite was carried out using time-of-flight secondary ion mass spectrometry (TOF-SEAS). Hydroxyapatite and fluorapatite were synthesized at 80 +/- 1 degrees C and pH 7.4 +/- 0.2. Fluorapatite was better crystallized, with its (300) reflection shifted to a slightly higher angle. High-resolution transmission electron microscopy clearly revealed a typical, regular hexagonal cross section perpendicular to the c-axis for fluorapatite and a flattened hexagonal cross section for hydroxyapatite. FT-IR spectra of fluorapatite confirmed the absence of OH absorption peak - which was seen in hydroxyapatite at about 3570 cm(-1). TOF-SIMS mass spectra showed a peak at 40 amu due to calcium. In addition, a peak at 19 amu due to fluorine could be clearly seen, although the intensities Of PO, PO2, and PO3 were very low. It was confirmed that TOF-SIMS clearly showed the differences between positive and negative mass spectra of hydroxyapatite and fluorapatite, especially for F-. We concluded that TOF-SIMS exhibited distinct advantages compared with other methods of analysis.

Fabrication of Al2O3/BN nanocomposites by chemical processing and their mechanical properties

T Kusunose, YH Kim, T Sekino, T Matsumoto, N Tanaka, T Nakayama, K Niihara

JOURNAL OF MATERIALS RESEARCH 20 ( 1 ) 183 - 190 2005年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MATERIALS RESEARCH SOCIETY

Al2O3/BN nanocomposites were fabricated through a novel chemical route involving hot-pressing of alpha-Al2O3 powders covered partly with turbostratic BN (t-BN). The nano-sized hexagonal BN (h-BN) particles were found to be homogeneously dispersed within the Al2O3 grains as well as at grain boundaries, which is indicative of nanocomposite structures. Thus, the present nanocomposites exhibited the unique properties of high strength and low Young's modulus associated with nanocomposites. This paper discusses in detail the synthesis process and microstructural features of these materials.

DOI： 10.1557/JMR.2005.0010

Osteopontin-derived peptide SVVYGLR induces angiogenesis in vivo 査読

Y Hamada, K Yuki, M Okazaki, W Fujitani, T Matsumoto, MK Hashida, K Harutsugu, K Nokihara, M Daito, N Matsuura, J Takahashi

DENTAL MATERIALS JOURNAL 23 ( 4 ) 650 - 655 2004年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPANESE SOC DENTAL MATERIALS DEVICES

Our previous study reported that an osteopontin-derived peptide SVVYGLR activates the adhesion, migration and tube formation abilities of endothelial cells in vitro. The present study investigated angiogenesis due to synthetic SVVYGLR and mutant peptides in vivo. Mutant peptides (n = 7) were synthesized by substituting alanine (A) for one of the 7 amino acids comprising SVVYGLR. In dorsal air sac assay, mouse dorsal skin 5 days after implantation of a chamber filled with SVVYGLR had approximately the same number of newly formed blood vessels to that filled with vascular endothelial growth factor (VEGF). The ability of angiogenesis due to SVVAGLR was significantly lower than that due to other 6 mutant peptides and SVVYGLR. This indicates that tyrosine (Y) plays an important role in angiogenesis due to SVVYGLR.

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