Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device

Pharmaceutics

Giulio Ghersi¹  Eimear B. Dolan²  Karina C. Scheiner³  Robbert J. Kok³  Wim E. Hennink³  Robert Wylie⁴  Garry P. Duffy⁴  Scott T. Robinson⁴  Ruth E. Levey⁴  Peter Dockery⁴  Mark Canney⁴  Liam P. Burke⁵  Thanh T. Nguyen⁶  Rob Steendam⁶  Helena M. Kelly⁷  Liam McDonough⁷  Fergal B. Coulter⁸  Stefano Deotti⁸  Eoin O’Cearbhaill⁸ 

[1] ABIEL srl, Viale delle Scienze ed.16, 90128 Palermo, Italy;Department of Biomedical Engineering, School of Engineering, College of Science and Engineering, H91 W5P7 Galway, Ireland;Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands;Discipline of Anatomy & Regenerative Medicine Institute, School of Medicine, College of Medicine, Nursing and Health Sciences National University of Ireland Galway, H91 W5P7 Galway, Ireland;Discipline of Bacteriology, School of Medicine, National University of Ireland Galway, H91 W5P7 Galway, Ireland;InnoCore Pharmaceuticals B.V., L.J. Zielstraweg 1, 9713 GX Groningen, The Netherlands;School of Pharmacy, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland;UCD Centre for Biomedical Engineering, School of Mechanical and Materials Engineering, University College Dublin, D04 V1W8 Dublin, Ireland;

关键词: diabetes;    prevascularization;    drug delivery;    VEGF;    medical device;    multi-scale porosity;   

DOI  :  10.3390/pharmaceutics13122077

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown