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

Journal of Cellular and Molecular Medicine

Delia Projahn⁴  Sakine Simsekyilmaz⁴  Smriti Singh⁶  Isabella Kanzler⁴  Birgit K. Kramp³  Marcella Langer³  Alexandrina Burlacu⁸  Jürgen Bernhagen⁷  Doris Klee⁶  Alma Zernecke²  Tilman M. Hackeng⁵  Jürgen Groll¹  Christian Weber³  Elisa A. Liehn⁴ 

[1] Department and Chair of Functional Materials in Medicine and Dentistry, University of Würzburg, Würzburg, Germany;Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany;Institute for Cardiovascular Prevention (IPEK), University Hospital of the LMU Munich, Munich, Germany;Institute for Molecular Cardiovascular Research (IMCAR), Medical Faculty, RWTH Aachen University, Aachen, Germany;Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands;Interactive Material Research - DWI an der RWTH Aachen e.V and Institute for Technical and Macromolecular Chemistry, Aachen, Germany;Institute of Biochemistry and Molecular Cell Biology, Aachen, Germany;Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, Romania

关键词: heart failure;    chemokines;    therapy;    cardiovascular pharmacology;    remodelling;   

DOI  :  10.1111/jcmm.12225

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.