TY - JOUR
T1 - Vascular Endothelial Growth Factor-Releasing Microspheres Based on Poly(ε-Caprolactone-PEG-ε-Caprolactone)-b-Poly(L-Lactide) Multiblock Copolymers Incorporated in a Three-Dimensional Printed Poly(Dimethylsiloxane) Cell Macroencapsulation Device
AU - Ghersi, Giulio
AU - O'Cearbhaill, Eoin D.
AU - Duffy, Garry P.
AU - Coulter, Fergal
AU - Nguyen, Thanh T.
AU - Scheiner, Karina C.
AU - Steendam, Rob
AU - Ghersi, Giulio
AU - Hennink, Wim E.
AU - Kok, Robbert J.
AU - Maas-Bakker, Roel F.
PY - 2019
Y1 - 2019
N2 - Pancreatic islet transplantation is a promising advanced therapy that has been used to treat patients suffering from diabetes type 1. Traditionally, pancreatic islets are infused via the portal vein, which is subsequently intended to engraft in the liver. Severe immunosuppressive treatments are necessary, however, to prevent rejection of the transplanted islets. Novel approaches therefore have focused on encapsulation of the islets in biomaterial implants which can protect the islets and offer an organ-like environment. Vascularization of the device’s surface is a prerequisite for the survival and proper func- tioning of transplanted pancreatic islets. We are pursuing a prevascularization strategy by incorporation of vascular endothelial growth factor (VEGF)-loaded microspheres in 3-dimensional printed poly(dimethylsiloxane)-based devices prior to their prospective loading with transplanted cells. Micro- spheres (~50 mm) were based on poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymers and were loaded with 10 mg VEGF/mg microspheres, and subsequently dispersed in a hy- aluronic acid carrier liquid. In vitro release studies at 37C demonstrated continuous release of fully bioactive VEGF for 4 weeks. In conclusion, our results demonstrate that incorporation of VEGF-releasing microspheres ensures adequate release of VEGF for a time window of 4 weeks, which is attractive in view of the vascularization of artificial pancreas implants.
AB - Pancreatic islet transplantation is a promising advanced therapy that has been used to treat patients suffering from diabetes type 1. Traditionally, pancreatic islets are infused via the portal vein, which is subsequently intended to engraft in the liver. Severe immunosuppressive treatments are necessary, however, to prevent rejection of the transplanted islets. Novel approaches therefore have focused on encapsulation of the islets in biomaterial implants which can protect the islets and offer an organ-like environment. Vascularization of the device’s surface is a prerequisite for the survival and proper func- tioning of transplanted pancreatic islets. We are pursuing a prevascularization strategy by incorporation of vascular endothelial growth factor (VEGF)-loaded microspheres in 3-dimensional printed poly(dimethylsiloxane)-based devices prior to their prospective loading with transplanted cells. Micro- spheres (~50 mm) were based on poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymers and were loaded with 10 mg VEGF/mg microspheres, and subsequently dispersed in a hy- aluronic acid carrier liquid. In vitro release studies at 37C demonstrated continuous release of fully bioactive VEGF for 4 weeks. In conclusion, our results demonstrate that incorporation of VEGF-releasing microspheres ensures adequate release of VEGF for a time window of 4 weeks, which is attractive in view of the vascularization of artificial pancreas implants.
UR - http://hdl.handle.net/10447/465578
M3 - Article
VL - 109
SP - 863
EP - 870
JO - International Journal of Pharmaceutical Sciences
JF - International Journal of Pharmaceutical Sciences
SN - 0975-4725
ER -