TY - JOUR
T1 - Controlled basic fibroblast growth factor release device made of poly(ethyleneglycol) dimethacrylates for creating a subcutaneous neovascular bed for cell transplantation
AU - Yamada, Shinji
AU - Nagai, Nobuhiro
AU - Saijo, Saaya
AU - Kaji, Hirokazu
AU - Nishizawa, Matsuhiko
AU - Imura, Kozue
AU - Goto, Masafumi
AU - Abe, Toshiaki
N1 - Funding Information:
Additional Supporting Information may be found in the online version of this article. †These authors contributed equally to this work. Correspondence to: Toshiaki Abe, Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; e-mail: toshi@oph.med.tohoku.ac.jp Contract grant sponsor: Grant for Basic Science and Platform Technology Program for Innovative Biological Medicine FIGURE 1. A: Schematic image of the capsule. B: Photographs show a component of capsule device, which consists of a reservoir made of TEGDM (left), drug pelletized with PEGDM/water (middle), and a cover made of TEGDM (right). C: Magnified photo of the pore in the reservoir or cover. D: Assembled device from the three components. Scale bar; (B, D) 10 mm and (C) 200 µm.
PY - 2017/11
Y1 - 2017/11
N2 - Subcutaneous space is a potential site for the transplantation of cells such as islets for treatment of type 1 diabetes. To enhance engraftment, an optimal space for the growth of the transplanted cells is needed along with neovascularization. In this study, we developed a device using a photocurable resin, poly(ethyleneglycol) dimethacrylates (PEGDM), for controlled release of basic fibroblast growth factor (bFGF) to create a subcutaneous neovascular bed in rats. The device consists of a disk-shaped capsule with micropores and is composed of tri(ethyleneglycol) dimethacrylate (TEGDM) and a drug formulation of PEGDM. The release rate was tuned by changing the number of pores and the composition of water and PEGDM in the drug formulation. bFGF released from devices incubated in phosphate-buffered saline (PBS) enhanced the growth of fibroblasts, indicating bioactivity of bFGF after release. Histological evaluation showed a significant increase in the extent of vasculature that was dependent on the amount of bFGF loaded into the device. A perfusion study using fluorescein isothiocyanate dextran 2000 kDa showed linear and capillary staining patterns, indicating potent functional vasculature. In conclusion, the controlled bFGF releasing device could provide a neovascular bed with the required vascularization in the subcutaneous space.
AB - Subcutaneous space is a potential site for the transplantation of cells such as islets for treatment of type 1 diabetes. To enhance engraftment, an optimal space for the growth of the transplanted cells is needed along with neovascularization. In this study, we developed a device using a photocurable resin, poly(ethyleneglycol) dimethacrylates (PEGDM), for controlled release of basic fibroblast growth factor (bFGF) to create a subcutaneous neovascular bed in rats. The device consists of a disk-shaped capsule with micropores and is composed of tri(ethyleneglycol) dimethacrylate (TEGDM) and a drug formulation of PEGDM. The release rate was tuned by changing the number of pores and the composition of water and PEGDM in the drug formulation. bFGF released from devices incubated in phosphate-buffered saline (PBS) enhanced the growth of fibroblasts, indicating bioactivity of bFGF after release. Histological evaluation showed a significant increase in the extent of vasculature that was dependent on the amount of bFGF loaded into the device. A perfusion study using fluorescein isothiocyanate dextran 2000 kDa showed linear and capillary staining patterns, indicating potent functional vasculature. In conclusion, the controlled bFGF releasing device could provide a neovascular bed with the required vascularization in the subcutaneous space.
KW - basic fibroblast growth factor
KW - drug delivery system
KW - islet transplantation
KW - poly(ethyleneglycol) dimethacrylate
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U2 - 10.1002/jbm.a.36153
DO - 10.1002/jbm.a.36153
M3 - Article
C2 - 28707305
AN - SCOPUS:85030460416
VL - 105
SP - 3017
EP - 3024
JO - Journal of Biomedical Materials Research
JF - Journal of Biomedical Materials Research
SN - 1549-3296
IS - 11
ER -
