{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:21:14Z","timestamp":1791048074067,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T00:00:00Z","timestamp":1638576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["645991"],"award-info":[{"award-number":["645991"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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(\u03b5-caprolactone-PEG-\u03b5-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. \u2212VEGF 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics13122077","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T03:10:38Z","timestamp":1638760238000},"page":"2077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device"],"prefix":"10.3390","volume":"13","author":[{"given":"Ruth E.","family":"Levey","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fergal B.","family":"Coulter","sequence":"additional","affiliation":[{"name":"UCD Centre for Biomedical Engineering, School of Mechanical and Materials Engineering, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina C.","family":"Scheiner","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Deotti","sequence":"additional","affiliation":[{"name":"UCD Centre for Biomedical Engineering, School of Mechanical and Materials Engineering, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T.","family":"Robinson","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"McDonough","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland"},{"name":"Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RSCI), D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"InnoCore Pharmaceuticals B.V., L.J. 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Zielstraweg 1, 9713 GX Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Canney","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Wylie","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-5174","authenticated-orcid":false,"given":"Liam P.","family":"Burke","sequence":"additional","affiliation":[{"name":"Discipline of Bacteriology, School of Medicine, National University of Ireland Galway, H91 W5P7 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6742-8461","authenticated-orcid":false,"given":"Eimear B.","family":"Dolan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Engineering, College of Science and Engineering, H91 W5P7 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dockery","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4925-0759","authenticated-orcid":false,"given":"Helena M.","family":"Kelly","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland"},{"name":"Tissue Engineering Research Group (TERG), Department of Anatomy, Royal College of Surgeons in Ireland (RSCI), D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Ghersi","sequence":"additional","affiliation":[{"name":"ABIEL srl, Viale delle Scienze ed.16, 90128 Palermo, Italy"},{"name":"Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Universit\u00e0 degli Studi di Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim E.","family":"Hennink","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4933-3968","authenticated-orcid":false,"given":"Robbert J.","family":"Kok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4666-5863","authenticated-orcid":false,"given":"Eoin","family":"O\u2019Cearbhaill","sequence":"additional","affiliation":[{"name":"UCD Centre for Biomedical Engineering, School of Mechanical and Materials Engineering, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry P.","family":"Duffy","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1177\/096368970000900114","article-title":"Improved Vascularization of Planar Membrane Diffusion Devices following Continuous Infusion of Vascular Endothelial Growth Factor","volume":"9","author":"Trivedi","year":"2000","journal-title":"Cell Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/0167-5699(96)10053-8","article-title":"Autoimmune diabetes: The role of the islets of langerhans","volume":"17","author":"Boitard","year":"1996","journal-title":"Immunol. 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