A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction

Awada, Hassan; Long, Daniel W.; Wang, Zhaohui; Hwang, Mintai P.; Kim, K.; Wang, Y.

doi:10.1016/j.biomaterials.2017.02.020

Cited by 68 publications

(74 citation statements)

References 79 publications

(109 reference statements)

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“…In this study, heparin was selected as the surface modifier to be conjugated on the PLLA/PLGA/PCL scaffold, because it possesses strong binding affinity with various bioactive factors. [30][31][32] The amount of heparin conjugated on the scaffold surface was measured to be 12.10±0.84 µg/cm 2 by toluidine blue assay. 19 Then, PDGF-BB was immobilized on the surface of heparinized scaffold via electrostatic interaction to enhance the interactions of SMCs with the nanofibrous scaffold.…”

Section: Immobilization Of Pdgf-bb and Enhanced Bioactivities Of Hvsmcsmentioning

confidence: 99%

Macroporous nanofibrous vascular scaffold with improved biodegradability and smooth muscle cells infiltration prepared by dual phase separation technique

Wang¹,

Nie²,

Liu³

et al. 2018

IJN

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IntroductionThe fast degradation of vascular graft and the infiltration of smooth muscle cells (SMCs) into the vascular graft are considered to be critical for the regeneration of functional neo-vessels. In our previous study, a novel dual phase separation technique was developed to one-pot prepare macroporous nanofibrous poly(L-lactic acid) (PLLA)/poly(ε-caprolactone) (PCL) vascular scaffold by phase separating the immiscible polymer blend. However, the slow degradation of PLLA/PCL limited cell infiltration. Herein, we hypothesized that poly(lactic-co-glycolic acid) (PLGA) would be miscible with PLLA but immiscible with PCL. Then, PLGA can be introduced into the PLLA/PCL blend to fabricate macroporous nanofibrous scaffold with improved biodegradability by using dual phase separation technique.Materials and methodsThe miscibility of PLGA with PLLA and PCL was evaluated. Then, the PLLA/PLGA/PCL scaffold was prepared by dual phase separation technique. The prepared scaffolds were characterized in terms of the morphology, in vitro degradation, mechanical properties, and cells’ infiltration and viability for human vascular SMCs (HVSMCs). Finally, platelet-derived growth factor-BB (PDGF-BB) was immobilized on the scaffold and its effect on the bioactivity of HVSMCs was studied.ResultsPLGA is miscible with PLLA but immiscible with PCL as hypothesized. The addition of PLGA enlarged the pore size and improved the biodegradability of composite scaffold. Notably, PLLA/PLGA/PCL scaffold with the blend ratio of 30:40:30 possessed improved pore interconnectivity for cells’ infiltration and enough mechanical properties. Moreover, HVSMCs could grow and infiltrate into this scaffold, and surface modification with PDGF-BB on the nanofibrous scaffold enhanced HVSMCs migration and proliferation.ConclusionThis study provides a strategy to expand dual phase separation technique into utilizing ternary even multinary polymer blend to fabricate macroporous nanofibrous scaffold with improved physicochemical properties. The prepared PLLA/PLGA/PCL scaffold would be promising for the regeneration of functional tunica media in vascular tissue engineering.

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Section: Immobilization Of Pdgf-bb and Enhanced Bioactivities Of Hvsmcsmentioning

confidence: 99%

Macroporous nanofibrous vascular scaffold with improved biodegradability and smooth muscle cells infiltration prepared by dual phase separation technique

Wang¹,

Nie²,

Liu³

et al. 2018

IJN

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“…To assess the process of angiogenesis, immunofluorescent staining for von Willebrand factor (vWF) and alpha‐smooth muscle actin (α‐SMA) which conjointly serve as the markers of mature neovessels was performed. Figure D reveals that different degree of angiogenesis is observed except for normal group since angiogenesis do not happen in healthy myocardium . More pronounced vWF+ neovessels are generated in HPAE–Py/Geln group compared to the MI and HPAE/Geln group (Figure E1).…”

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confidence: 95%

Paintable and Rapidly Bondable Conductive Hydrogels as Therapeutic Cardiac Patches

et al. 2018

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In recent years, cardiac patches have been developed for the treatment of myocardial infarction. However, the fixation approaches onto the tissue through suture or phototriggered reaction inevitably cause new tissue damage. Herein, a paintable hydrogel is constructed based on Fe -triggered simultaneous polymerization of covalently linked pyrrole and dopamine in the hyperbranched chains where the in situ formed conductive polypyrrole also uniquely serves to crosslink network. This conductive and adhesive hydrogel can be conveniently painted as a patch onto the heart surface without adverse liquid leakage. The functional patch whose conductivity is equivalent to that of normal myocardium is strongly bonded to the beating heart within 4 weeks, accordingly efficiently boosting the transmission of electrophysiological signals. Eventually, the reconstruction of cardiac function and revascularization of the infarct myocardium are remarkably improved. The translatable suture-free strategy reported in this work is promising to address the human clinical challenges in cardiac tissue engineering.

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“…Rat hearts were excised, and the atrium, blood clots and fibrous tissue around the heart were removed. Then, the heart was minced into 1-mm 3 pieces in an aseptic culture dish with 4 ℃ phosphate buffer solution (PBS) under sterile conditions. The pieces were then washed three times with PBS to remove impurities.…”

Section: Nrvm Isolation and Culturementioning

confidence: 99%

“…Sudden cardiac death (SCD), which is mainly caused by ventricular tachyarrhythmia, is the leading cause of death in myocardial infarction (MI) patients. Beneficial effects on infarction size, systolic function and ventricular remodeling have been found with factor-based therapy in MI (2,3). The combination of insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF), mostly as an adjunct to stem cell therapy, has already been well studied and has been shown to have considerable efficacy in myocardial repair (4,5).…”

Section: Introductionmentioning

confidence: 99%

Combination of HGF and IGF-1 promotes connexin 43 expression and improves ventricular arrhythmia after myocardial infarction through activating the MAPK/ERK and MAPK/p38 signaling pathways in a rat model

Yao¹,

Ke²,

Zhou³

et al. 2019

Cardiovasc. Diagn. Ther.

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Background: In this study, we hypothesized that the combination of hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) alters the expression of connexin 43 (Cx43) and results in a reduced frequency of induced ventricular arrhythmia in rats after myocardial infarction (MI) and explored the preliminary mechanisms involved. Methods: Cardiomyocytes were cultured in vitro in medium with PBS, HGF, IGF-1, GFs (HGF + IGF-1), HGF + p38 inhibitor, HGF + ERK inhibitor, IGF-1 + p38 inhibitor or IGF-1 + ERK inhibitor. The expression of Cx43 was tested by real-time PCR and Western blotting after 48 hours. MI was induced in 48 male Sprague-Dawley rats. The rats were randomly divided into four groups and received an injection of PBS, HGF, IGF-1 or GFs into the infarct border zone two weeks after MI. Six weeks after injection, the expression levels of Cx43 and programmed stimulation-induced ventricular arrhythmias were examined. Results: In vitro, the expression of Cx43 mRNA and the Cx43 protein in cardiomyocytes was higher in the HGF, IGF-1, and GFs groups than in the PBS group. GFs had a combinatorial effect on the Cx43 mRNA level but not on the Cx43 protein level. There was a significant reduction in Cx43 mRNA and Cx43 protein levels in the IGF-1 + p38 inhibitor group and IGF-1 + ERK inhibitor group compared to the IGF-1 group. In vivo, programmed stimulation significantly decreased the frequency of ventricular arrhythmia in the GFs, HGF and IGF-1 groups, and this effect was accompanied by increased immunohistochemical staining for Cx43, myocardial Cx43 protein levels and Cx43 mRNA levels in the infarct border zone of the left ventricle compared with those in the PBS group. The combinatorial effect of GFs on Cx43 expression was only observed at the mRNA level. Conclusions: Both HGF and IGF-1 enhanced the expression of Cx43 and improved induced ventricular arrhythmia in rats with MI. Both synergistic and antagonistic effects of HGF and IGF-1 were not observed. In addition, IGF-1 may function through the MAPK/p38 and ERK1/2 signaling pathways to regulate Cx43 expression.

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A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction

Cited by 68 publications

References 79 publications

Macroporous nanofibrous vascular scaffold with improved biodegradability and smooth muscle cells infiltration prepared by dual phase separation technique

Macroporous nanofibrous vascular scaffold with improved biodegradability and smooth muscle cells infiltration prepared by dual phase separation technique

Paintable and Rapidly Bondable Conductive Hydrogels as Therapeutic Cardiac Patches

Combination of HGF and IGF-1 promotes connexin 43 expression and improves ventricular arrhythmia after myocardial infarction through activating the MAPK/ERK and MAPK/p38 signaling pathways in a rat model

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