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Adjustable delivery of pro-angiogenic FGF-2 by alginate:collagen microspheres

Therapeutic induction of blood vessel growth (angiogenesis) in ischemic tissues holds great potential for treatment of myocardial infarction and stroke. Achieving sustained angiogenesis and vascular maturation has, however, been highly challenging. Here, we demonstrate that alginate:collagen hydroge...

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Autores principales: Ali, Zaheer, Islam, Anik, Sherrell, Peter, Le-Moine, Mark, Lolas, Georgios, Syrigos, Konstantinos, Rafat, Mehrdad, Jensen, Lasse D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898261/
https://www.ncbi.nlm.nih.gov/pubmed/29449216
http://dx.doi.org/10.1242/bio.027060
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author Ali, Zaheer
Islam, Anik
Sherrell, Peter
Le-Moine, Mark
Lolas, Georgios
Syrigos, Konstantinos
Rafat, Mehrdad
Jensen, Lasse D.
author_facet Ali, Zaheer
Islam, Anik
Sherrell, Peter
Le-Moine, Mark
Lolas, Georgios
Syrigos, Konstantinos
Rafat, Mehrdad
Jensen, Lasse D.
author_sort Ali, Zaheer
collection PubMed
description Therapeutic induction of blood vessel growth (angiogenesis) in ischemic tissues holds great potential for treatment of myocardial infarction and stroke. Achieving sustained angiogenesis and vascular maturation has, however, been highly challenging. Here, we demonstrate that alginate:collagen hydrogels containing therapeutic, pro-angiogenic FGF-2, and formulated as microspheres, is a promising and clinically relevant vehicle for therapeutic angiogenesis. By titrating the amount of readily dissolvable and degradable collagen with more slowly degradable alginate in the hydrogel mixture, the degradation rates of the biomaterial controlling the release kinetics of embedded pro-angiogenic FGF-2 can be adjusted. Furthermore, we elaborate a microsphere synthesis protocol allowing accurate control over sphere size, also a critical determinant of degradation/release rate. As expected, alginate:collagen microspheres were completely biocompatible and did not cause any adverse reactions when injected in mice. Importantly, the amount of pro-angiogenic FGF-2 released from such microspheres led to robust induction of angiogenesis in zebrafish embryos similar to that achieved by injecting FGF-2-releasing cells. These findings highlight the use of microspheres constructed from alginate:collagen hydrogels as a promising and clinically relevant delivery system for pro-angiogenic therapy.
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spelling pubmed-58982612018-04-13 Adjustable delivery of pro-angiogenic FGF-2 by alginate:collagen microspheres Ali, Zaheer Islam, Anik Sherrell, Peter Le-Moine, Mark Lolas, Georgios Syrigos, Konstantinos Rafat, Mehrdad Jensen, Lasse D. Biol Open Research Article Therapeutic induction of blood vessel growth (angiogenesis) in ischemic tissues holds great potential for treatment of myocardial infarction and stroke. Achieving sustained angiogenesis and vascular maturation has, however, been highly challenging. Here, we demonstrate that alginate:collagen hydrogels containing therapeutic, pro-angiogenic FGF-2, and formulated as microspheres, is a promising and clinically relevant vehicle for therapeutic angiogenesis. By titrating the amount of readily dissolvable and degradable collagen with more slowly degradable alginate in the hydrogel mixture, the degradation rates of the biomaterial controlling the release kinetics of embedded pro-angiogenic FGF-2 can be adjusted. Furthermore, we elaborate a microsphere synthesis protocol allowing accurate control over sphere size, also a critical determinant of degradation/release rate. As expected, alginate:collagen microspheres were completely biocompatible and did not cause any adverse reactions when injected in mice. Importantly, the amount of pro-angiogenic FGF-2 released from such microspheres led to robust induction of angiogenesis in zebrafish embryos similar to that achieved by injecting FGF-2-releasing cells. These findings highlight the use of microspheres constructed from alginate:collagen hydrogels as a promising and clinically relevant delivery system for pro-angiogenic therapy. The Company of Biologists Ltd 2018-02-15 /pmc/articles/PMC5898261/ /pubmed/29449216 http://dx.doi.org/10.1242/bio.027060 Text en © 2018. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Ali, Zaheer
Islam, Anik
Sherrell, Peter
Le-Moine, Mark
Lolas, Georgios
Syrigos, Konstantinos
Rafat, Mehrdad
Jensen, Lasse D.
Adjustable delivery of pro-angiogenic FGF-2 by alginate:collagen microspheres
title Adjustable delivery of pro-angiogenic FGF-2 by alginate:collagen microspheres
title_full Adjustable delivery of pro-angiogenic FGF-2 by alginate:collagen microspheres
title_fullStr Adjustable delivery of pro-angiogenic FGF-2 by alginate:collagen microspheres
title_full_unstemmed Adjustable delivery of pro-angiogenic FGF-2 by alginate:collagen microspheres
title_short Adjustable delivery of pro-angiogenic FGF-2 by alginate:collagen microspheres
title_sort adjustable delivery of pro-angiogenic fgf-2 by alginate:collagen microspheres
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898261/
https://www.ncbi.nlm.nih.gov/pubmed/29449216
http://dx.doi.org/10.1242/bio.027060
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