Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction

  • Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.

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Author:Delia Projahn, Sakine Simsekyilmaz, Smriti Singh, Isabella Kanzler, Birgit K. Kramp, Marcella Langer, Alexandrina Burlacu, Jürgen BernhagenGND, Doris Klee, Alma Zernecke, Tilman M. Hackeng, Jürgen Groll, Christian Weber, Elisa A. Liehn, Rory R. Koenen
URN:urn:nbn:de:hebis:30:3-336234
URL:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119385/
DOI:https://doi.org/10.1111/jcmm.12225
ISSN:1582-1838
ISSN:1582-4934
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24512349
Parent Title (English):Journal of cellular and molecular medicine
Publisher:Wiley-Blackwell
Place of publication:Hoboken, NJ
Document Type:Article
Language:English
Date of Publication (online):2014/02/06
Date of first Publication:2014/02/06
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2015/01/21
Tag:cardiovascular pharmacology; chemokines; heart failure; remodelling; therapy
Volume:18
Issue:5
Page Number:11
First Page:790
Last Page:800
Note:
This is an open access article under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/ , which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
HeBIS-PPN:367162326
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0