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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-116597
  • 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 siteMyocardial 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 24hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4weeks. 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.show moreshow less

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Author: Delia Projahn, Sakine Simsekyilmaz, Smriti Singh, Isabella Kanzler, Birgit K. Kramp, Marcella Langer, Alexandrina Burlacu, Jürgen Bernhagen, Doris Klee, Alma Zernecke, Tilman M. Hackeng, Jürgen Groll, Christian Weber, Elisa A. Liehn, Roy R. Koenen
URN:urn:nbn:de:bvb:20-opus-116597
Document Type:Journal article
Faculties:Medizinische Fakultät / Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde
Language:English
Parent Title (English):Journal of Cellular and Molecular Medicine
ISSN:1582-4934
Year of Completion:2014
Volume:18
Issue:5
Pagenumber:790-800
Source:Journal of Cellular and Molecular Medicine Vol 18, No 5, 2014 pp. 790-800. doi:10.1111/jcmm.12225
DOI:https://doi.org/10.1111/jcmm.12225
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24512349
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:cardiovascular pharmacology; chemokines; endothelial progenitor cells; factor-I; heart-failure; left-ventricular function; rat model; recruitment; remodelling; therapy
Release Date:2015/08/03
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung