| Autor: |
Ruth E. Levey, Fergal B. Coulter, Karina C. Scheiner, Stefano Deotti, Scott T. Robinson, Liam McDonough, Thanh T. Nguyen, Rob Steendam, Mark Canney, Robert Wylie, Liam P. Burke, Eimear B. Dolan, Peter Dockery, Helena M. Kelly, Giulio Ghersi, Wim E. Hennink, Robbert J. Kok, Eoin O’Cearbhaill, Garry P. Duffy |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Pharmaceutics, Vol 13, Iss 12, p 2077 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4923 |
| DOI: |
10.3390/pharmaceutics13122077 |
| Popis: |
Macroencapsulation systems have been developed to improve islet cell transplantation but can induce a foreign body response (FBR). The development of neovascularization adjacent to the device is vital for the survival of encapsulated islets and is a limitation for long-term device success. Previously we developed additive manufactured multi-scale porosity implants, which demonstrated a 2.5-fold increase in tissue vascularity and integration surrounding the implant when compared to a non-textured implant. In parallel to this, we have developed poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymer microspheres containing VEGF, which exhibited continued release of bioactive VEGF for 4-weeks in vitro. In the present study, we describe the next step towards clinical implementation of an islet macroencapsulation device by combining a multi-scale porosity device with VEGF releasing microspheres in a rodent model to assess prevascularization over a 4-week period. An in vivo estimation of vascular volume showed a significant increase in vascularity (* p = 0.0132) surrounding the +VEGF vs. −VEGF devices, however, histological assessment of blood vessels per area revealed no significant difference. Further histological analysis revealed significant increases in blood vessel stability and maturity (** p = 0.0040) and vessel diameter size (*** p = 0.0002) surrounding the +VEGF devices. We also demonstrate that the addition of VEGF microspheres did not cause a heightened FBR. In conclusion, we demonstrate that the combination of VEGF microspheres with our multi-scale porous macroencapsulation device, can encourage the formation of significantly larger, stable, and mature blood vessels without exacerbating the FBR. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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