کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6450796 1416142 2017 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction
چکیده انگلیسی

After myocardial infarction (MI), the heart undergoes fibrotic pathological remodeling instead of repair and regeneration. With multiple pathologies developing after MI, treatment using several proteins is expected to address this range of pathologies more effectively than a single-agent therapy. A factorial design of experiments study guided us to combine three complementary factors in one injection: tissue inhibitor of metalloproteinases-3 (TIMP-3) was embedded in a fibrin gel for signaling in the initial phase of the treatment, while basic fibroblast growth factor (FGF-2) and stromal cell-derived factor 1-alpha (SDF-1α) were embedded in heparin-based coacervates for sustained release and distributed within the same fibrin gel to exert their effects over a longer period. The gel was then tested in a rat model of myocardial infarction. Contractility of rat hearts treated with the protein coacervate-gel composite stabilized and slightly improved after the first week while contractility continued to decrease in rats treated with free proteins or saline over the 8 week study period. Hearts receiving the protein coacervate-gel composite treatment also exhibited reduced ventricular dilation, inflammation, fibrosis, and extracellular matrix (ECM) degradation. Revascularization, cardiomyocyte preservation, stem cell homing, and increased myocardial strain likely all contributed to the repair. This study demonstrates the potential of a multifactorial therapeutic approach in MI, using three complementary proteins delivered sequentially for comprehensive healing. The study also shows the necessity of controlled delivery for growth factors and cytokines to be an effective treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 125, May 2017, Pages 65-80
نویسندگان
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