| 1. |
- Cimenci, Cagla Eren, et al.
(författare)
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Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Prevents Adverse Remodeling and Improves Cardiac Function Post-Myocardial Infarction
- 2022
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Ingår i: Advanced Functional Materials. - : WILEY-V C H VERLAG GMBH. - 1616-301X .- 1616-3028. ; 32:1
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Tidskriftsartikel (refereegranskat)abstract
- Methylglyoxal (MG) is a highly reactive dicarbonyl and the main precursor of advanced glycation end-products (AGEs). After myocardial infarction (MI), MG-derived AGEs accumulate in the heart and contribute to adverse remodeling and loss of cardiac function. In this study, the flavonoid fisetin, a dicarbonyl scavenger, is used to reduce the negative effects of MG in the post-MI heart. A fisetin-loaded collagen type I hydrogel (fisetin-HG) is injected intramyocardially in mice at 3 h post-MI, and compared to fisetin-alone, hydrogel-alone, or saline treatment. Fisetin-HG treatment increases the level of glyoxalase-1 (the main MG-metabolizing enzyme), reduces MG-AGE accumulation, and decreases oxidative stress in the MI heart, which is associated with smaller scar size and improved cardiac function. Treatment with fisetin-HG also promotes neovascularization and increases the number of pro-healing macrophages in the infarct area, while reducing the number of pro-inflammatory macrophages. Taken together, the results demonstrate that the fisetin-collagen hydrogel therapy can reduce the accumulation and negative effects of MG post-MI. This therapy may be a promising approach to limit adverse cardiac remodeling, prevent damage, and preserve function of the infarcted heart.
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| 2. |
- Pupkaite, Justina, et al.
(författare)
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Delivering More of an Injectable Human Recombinant Collagen III Hydrogel Does Not Improve Its Therapeutic Efficacy for Treating Myocardial Infarction
- 2020
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Ingår i: ACS Biomaterials Science & Engineering. - : AMER CHEMICAL SOC. - 2373-9878. ; 6:7, s. 4256-4265
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Tidskriftsartikel (refereegranskat)abstract
- Injectable hydrogels are a promising method to enhance repair in the heart after myocardial infarction (MI). However, few studies have compared different strategies for the application of biomaterial treatments. In this study, we use a clinically relevant mouse MI model to assess the therapeutic efficacy of different treatment protocols for intramyocardial injection of a recombinant human collagen III (rHCIII) thermoresponsive hydrogel. Comparing a single hydrogel injection at an early time point (3 h) versus injections at multiple time points (3 h, 1 week, and 2 weeks) post-MI revealed that the single injection group led to superior cardiac function, reduced scar size and inflammation, and increased vascularization. Omitting the 3 h time point and delivering the hydrogel at 1 and 2 weeks post-MI led to poorer cardiac function. The positive effects of the single time point injection (3 h) on scar size and vascular density were lost when the hydrogels collagen concentration was increased from 1% to 2%, and it did not confer any additional functional improvement. This study shows that early treatment with a rHCIII hydrogel can improve cardiac function post-MI but that injecting more rHCIII (by increased concentration or more over time) can reduce its efficacy, thus highlighting the importance of investigating optimal treatment strategies of biomaterial therapy for MI.
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