Vascular endothelial growth factor promotes brain tissue regeneration with a novel biomaterial polydimethylsiloxane-tetraethoxysilane

HanZhe Zhang, Takeshi Hayashi, Kanji Tsuru, Kentaro Deguchi, Mitsuyuki Nagahara, Satoshi Hayakawa, Makiko Nagai, Tatsushi Kamiya, Akiyoshi Osaka, Koji Abe

Research output: Contribution to journalArticle

Abstract

Background: Injury of the central nervous system (CNS) of mammals may cause irreparable damage due to the limited regeneration capacity of the tissue. In order for the CNS tissue to regenerate, to supply a scaffold for the newly produced cells to adhere is necessary. Application of biodegradable polymers such as collagen, gelatin, fibrin and alginates has been investigated for organ damage other than the CNS. In this context, we recently produced a novel biomaterial from polydimethylsiloxane (PDMS) and tetraethoxysilane (TEOS). We added the most potent angiogenic factor vascular endothelial growth factor (VEGF) and observed the difference in brain regenerative process in the PDMS-TEOS scaffold. Methods: Male Wistar rats of 12 weeks old were anesthetized and placed in a stereotaxic apparatus. A piece of bone over the right frontal cortex was excised, and 2 x 5 mm defect in the brain was made by cutting and aspiration. The defect was positioned from 1.0 mm anterior to 4.0 mm posterior of the bregma and 2.0 to 4.0 mm lateral to the midline. The depth of the lesion was 2.0 mm from the brain surface. The block of PDMS-TEOS scaffold, with or without VEGF, was placed into the lesion immediately after making the defect. The animals were sacrificed at 30 days after PDMS-TEOS scaffold implantation. For histological analysis of the newly formed tissue, the sections were stained with HE. In order to identify cell types in the newly formed tissue, we performed immunohistochemical analysis for glial fibrillary acidic protein (GFAP), an astrocyte marker, and N-acetylglucosamine oligomer (NAGO), an endothelial cells marker. In order to determine whether the cells in PDMS-TEOS scaffold were under mitosis, we carried out double fluorescent study for cell phenotype markers and Ki67. Result: The PDMS-TEOS scaffold remained at the implanted site for 30 days and kept the integrity of brain shape (Fig. A and B). HE staining showed that a small number of cells infiltrated into the PDMS-TEOS scaffold even without VEGF at 30 days after the implantation, but that addition of VEGF significantly increased the number of infiltrated cells NAGO staining showed only a few positive cells in the PDMS-TEOS scaffold without VEGF, but significant increase of endothelial cells with VEGF was confirmed. Immunohistochemical study for GFAP demonstrated that only a few astrocytes were found in the PDMS-TEOS scaffold without VEGF, which was again significantly increased with VEGF. Double staining with proliferation maker Ki67 demonstrated that VEGF significantly increased newly formed astrocytes and endotheial cells, indicating that addition of VEGF accelerated tissue restoration and angiogenesis. Conclusions: The present study showed that a new porous PDMS-TEOS is a good candidate biomaterial for brain tissue restoration. Endothelial as well as glial cells successfully infiltrated into this biomaterial. Addition of VEGF further promoted new tissue formation.

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue numberSUPPL. 1
Publication statusPublished - Nov 13 2007

Fingerprint

Biocompatible Materials
Vascular Endothelial Growth Factor A
Regeneration
Brain
Astrocytes
Acetylglucosamine
Central Nervous System
Endothelial Cells
Glial Fibrillary Acidic Protein
Staining and Labeling
baysilon
tetraethoxysilane
Cell Count
Alginates
Nerve Tissue
Angiogenesis Inducing Agents
Frontal Lobe
Gelatin
Fibrin
Mitosis

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Vascular endothelial growth factor promotes brain tissue regeneration with a novel biomaterial polydimethylsiloxane-tetraethoxysilane. / Zhang, HanZhe; Hayashi, Takeshi; Tsuru, Kanji; Deguchi, Kentaro; Nagahara, Mitsuyuki; Hayakawa, Satoshi; Nagai, Makiko; Kamiya, Tatsushi; Osaka, Akiyoshi; Abe, Koji.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 27, No. SUPPL. 1, 13.11.2007.

Research output: Contribution to journalArticle

Zhang, HanZhe ; Hayashi, Takeshi ; Tsuru, Kanji ; Deguchi, Kentaro ; Nagahara, Mitsuyuki ; Hayakawa, Satoshi ; Nagai, Makiko ; Kamiya, Tatsushi ; Osaka, Akiyoshi ; Abe, Koji. / Vascular endothelial growth factor promotes brain tissue regeneration with a novel biomaterial polydimethylsiloxane-tetraethoxysilane. In: Journal of Cerebral Blood Flow and Metabolism. 2007 ; Vol. 27, No. SUPPL. 1.
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abstract = "Background: Injury of the central nervous system (CNS) of mammals may cause irreparable damage due to the limited regeneration capacity of the tissue. In order for the CNS tissue to regenerate, to supply a scaffold for the newly produced cells to adhere is necessary. Application of biodegradable polymers such as collagen, gelatin, fibrin and alginates has been investigated for organ damage other than the CNS. In this context, we recently produced a novel biomaterial from polydimethylsiloxane (PDMS) and tetraethoxysilane (TEOS). We added the most potent angiogenic factor vascular endothelial growth factor (VEGF) and observed the difference in brain regenerative process in the PDMS-TEOS scaffold. Methods: Male Wistar rats of 12 weeks old were anesthetized and placed in a stereotaxic apparatus. A piece of bone over the right frontal cortex was excised, and 2 x 5 mm defect in the brain was made by cutting and aspiration. The defect was positioned from 1.0 mm anterior to 4.0 mm posterior of the bregma and 2.0 to 4.0 mm lateral to the midline. The depth of the lesion was 2.0 mm from the brain surface. The block of PDMS-TEOS scaffold, with or without VEGF, was placed into the lesion immediately after making the defect. The animals were sacrificed at 30 days after PDMS-TEOS scaffold implantation. For histological analysis of the newly formed tissue, the sections were stained with HE. In order to identify cell types in the newly formed tissue, we performed immunohistochemical analysis for glial fibrillary acidic protein (GFAP), an astrocyte marker, and N-acetylglucosamine oligomer (NAGO), an endothelial cells marker. In order to determine whether the cells in PDMS-TEOS scaffold were under mitosis, we carried out double fluorescent study for cell phenotype markers and Ki67. Result: The PDMS-TEOS scaffold remained at the implanted site for 30 days and kept the integrity of brain shape (Fig. A and B). HE staining showed that a small number of cells infiltrated into the PDMS-TEOS scaffold even without VEGF at 30 days after the implantation, but that addition of VEGF significantly increased the number of infiltrated cells NAGO staining showed only a few positive cells in the PDMS-TEOS scaffold without VEGF, but significant increase of endothelial cells with VEGF was confirmed. Immunohistochemical study for GFAP demonstrated that only a few astrocytes were found in the PDMS-TEOS scaffold without VEGF, which was again significantly increased with VEGF. Double staining with proliferation maker Ki67 demonstrated that VEGF significantly increased newly formed astrocytes and endotheial cells, indicating that addition of VEGF accelerated tissue restoration and angiogenesis. Conclusions: The present study showed that a new porous PDMS-TEOS is a good candidate biomaterial for brain tissue restoration. Endothelial as well as glial cells successfully infiltrated into this biomaterial. Addition of VEGF further promoted new tissue formation.",
author = "HanZhe Zhang and Takeshi Hayashi and Kanji Tsuru and Kentaro Deguchi and Mitsuyuki Nagahara and Satoshi Hayakawa and Makiko Nagai and Tatsushi Kamiya and Akiyoshi Osaka and Koji Abe",
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AU - Zhang, HanZhe

AU - Hayashi, Takeshi

AU - Tsuru, Kanji

AU - Deguchi, Kentaro

AU - Nagahara, Mitsuyuki

AU - Hayakawa, Satoshi

AU - Nagai, Makiko

AU - Kamiya, Tatsushi

AU - Osaka, Akiyoshi

AU - Abe, Koji

PY - 2007/11/13

Y1 - 2007/11/13

N2 - Background: Injury of the central nervous system (CNS) of mammals may cause irreparable damage due to the limited regeneration capacity of the tissue. In order for the CNS tissue to regenerate, to supply a scaffold for the newly produced cells to adhere is necessary. Application of biodegradable polymers such as collagen, gelatin, fibrin and alginates has been investigated for organ damage other than the CNS. In this context, we recently produced a novel biomaterial from polydimethylsiloxane (PDMS) and tetraethoxysilane (TEOS). We added the most potent angiogenic factor vascular endothelial growth factor (VEGF) and observed the difference in brain regenerative process in the PDMS-TEOS scaffold. Methods: Male Wistar rats of 12 weeks old were anesthetized and placed in a stereotaxic apparatus. A piece of bone over the right frontal cortex was excised, and 2 x 5 mm defect in the brain was made by cutting and aspiration. The defect was positioned from 1.0 mm anterior to 4.0 mm posterior of the bregma and 2.0 to 4.0 mm lateral to the midline. The depth of the lesion was 2.0 mm from the brain surface. The block of PDMS-TEOS scaffold, with or without VEGF, was placed into the lesion immediately after making the defect. The animals were sacrificed at 30 days after PDMS-TEOS scaffold implantation. For histological analysis of the newly formed tissue, the sections were stained with HE. In order to identify cell types in the newly formed tissue, we performed immunohistochemical analysis for glial fibrillary acidic protein (GFAP), an astrocyte marker, and N-acetylglucosamine oligomer (NAGO), an endothelial cells marker. In order to determine whether the cells in PDMS-TEOS scaffold were under mitosis, we carried out double fluorescent study for cell phenotype markers and Ki67. Result: The PDMS-TEOS scaffold remained at the implanted site for 30 days and kept the integrity of brain shape (Fig. A and B). HE staining showed that a small number of cells infiltrated into the PDMS-TEOS scaffold even without VEGF at 30 days after the implantation, but that addition of VEGF significantly increased the number of infiltrated cells NAGO staining showed only a few positive cells in the PDMS-TEOS scaffold without VEGF, but significant increase of endothelial cells with VEGF was confirmed. Immunohistochemical study for GFAP demonstrated that only a few astrocytes were found in the PDMS-TEOS scaffold without VEGF, which was again significantly increased with VEGF. Double staining with proliferation maker Ki67 demonstrated that VEGF significantly increased newly formed astrocytes and endotheial cells, indicating that addition of VEGF accelerated tissue restoration and angiogenesis. Conclusions: The present study showed that a new porous PDMS-TEOS is a good candidate biomaterial for brain tissue restoration. Endothelial as well as glial cells successfully infiltrated into this biomaterial. Addition of VEGF further promoted new tissue formation.

AB - Background: Injury of the central nervous system (CNS) of mammals may cause irreparable damage due to the limited regeneration capacity of the tissue. In order for the CNS tissue to regenerate, to supply a scaffold for the newly produced cells to adhere is necessary. Application of biodegradable polymers such as collagen, gelatin, fibrin and alginates has been investigated for organ damage other than the CNS. In this context, we recently produced a novel biomaterial from polydimethylsiloxane (PDMS) and tetraethoxysilane (TEOS). We added the most potent angiogenic factor vascular endothelial growth factor (VEGF) and observed the difference in brain regenerative process in the PDMS-TEOS scaffold. Methods: Male Wistar rats of 12 weeks old were anesthetized and placed in a stereotaxic apparatus. A piece of bone over the right frontal cortex was excised, and 2 x 5 mm defect in the brain was made by cutting and aspiration. The defect was positioned from 1.0 mm anterior to 4.0 mm posterior of the bregma and 2.0 to 4.0 mm lateral to the midline. The depth of the lesion was 2.0 mm from the brain surface. The block of PDMS-TEOS scaffold, with or without VEGF, was placed into the lesion immediately after making the defect. The animals were sacrificed at 30 days after PDMS-TEOS scaffold implantation. For histological analysis of the newly formed tissue, the sections were stained with HE. In order to identify cell types in the newly formed tissue, we performed immunohistochemical analysis for glial fibrillary acidic protein (GFAP), an astrocyte marker, and N-acetylglucosamine oligomer (NAGO), an endothelial cells marker. In order to determine whether the cells in PDMS-TEOS scaffold were under mitosis, we carried out double fluorescent study for cell phenotype markers and Ki67. Result: The PDMS-TEOS scaffold remained at the implanted site for 30 days and kept the integrity of brain shape (Fig. A and B). HE staining showed that a small number of cells infiltrated into the PDMS-TEOS scaffold even without VEGF at 30 days after the implantation, but that addition of VEGF significantly increased the number of infiltrated cells NAGO staining showed only a few positive cells in the PDMS-TEOS scaffold without VEGF, but significant increase of endothelial cells with VEGF was confirmed. Immunohistochemical study for GFAP demonstrated that only a few astrocytes were found in the PDMS-TEOS scaffold without VEGF, which was again significantly increased with VEGF. Double staining with proliferation maker Ki67 demonstrated that VEGF significantly increased newly formed astrocytes and endotheial cells, indicating that addition of VEGF accelerated tissue restoration and angiogenesis. Conclusions: The present study showed that a new porous PDMS-TEOS is a good candidate biomaterial for brain tissue restoration. Endothelial as well as glial cells successfully infiltrated into this biomaterial. Addition of VEGF further promoted new tissue formation.

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