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Injectable Hydrogels Encapsulating Dual-Functional Au@Pt Core-Shell Nanoparticles Regulate Infarcted Microenvironments and Enhance the Therapeutic Efficacy of Stem Cells through Antioxidant and Electrical Integration.

ABSTRACT: Injectable functional biomaterials have made significant progress in cardiac regenerative. In addition, how to adjust the abominable infarction microenvironment and introduce therapeutic stem cells to improve the healing effect has become a hotspot. Herein, injectable stem cell vector is prepared by combining natural alginate hydrogel and Au@Pt nanoparticles (Au@Pt/Alg hydrogel) to encapsulate brown adipose stem cells (BASCs). Au@Pt nanoparticles with both antioxidative and conductive properties could effectively eliminate reactive oxygen species, enhance the frequency of action potential release of cardiomyocytes, and further reduce the inflammatory factors of macrophage in vitro. The Au@Pt/Alg hydrogel enhances the antioxidant, differentiation, and paracrine capability of BASCs. The effect of BASCs loaded Au@Pt/Alg hydrogel is evaluated in a rat myocardial infarction (MI) model. The antioxidant, anti-inflammatory, and heart electrical integration are showed in the MI model. More interestingly, Au@Pt/Alg hydrogel can effectively maintain the paracrine efficiency and pro-angiogenesis effects of BASCs in the infarcted area. This study led us to recognize the great value of Au@Pt/Alg hydrogels for their ability to actively regulate the microenvironment and carry stem cells for MI treatment.

SUBMITTER: Liu W

PROVIDER: S-EPMC9933615 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Injectable Hydrogels Encapsulating Dual-Functional Au@Pt Core-Shell Nanoparticles Regulate Infarcted Microenvironments and Enhance the Therapeutic Efficacy of Stem Cells through Antioxidant and Electrical Integration.

Liu Wei W Zhao Nana N Yin Qi Q Zhao Xiaoyi X Guo Kangli K Xian Yifan Y Li Siwei S Wang Chunlan C Zhu Miaomiao M Du Yurong Y Xu Fu-Jian FJ Wang Changyong C Zhou Jin J

ACS nano 20230125 3

Injectable functional biomaterials have made significant progress in cardiac regenerative. In addition, how to adjust the abominable infarction microenvironment and introduce therapeutic stem cells to improve the healing effect has become a hotspot. Herein, injectable stem cell vector is prepared by combining natural alginate hydrogel and Au@Pt nanoparticles (Au@Pt/Alg hydrogel) to encapsulate brown adipose stem cells (BASCs). Au@Pt nanoparticles with both antioxidative and conductive properties ...[more]

PMID: 36695873

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Project description:After myocardial infarction (MI), the scar tissue contributes to ventricular dysfunction by electrically uncoupling viable cardiomyocytes in the infarct region. Injection of a conductive hydrogel could not only provide mechanical support to the infarcted region, but also synchronize contraction and restore ventricular function by electrically connecting isolated cardiomyocytes to intact tissue. Methods: We created a conductive hydrogel by introducing graphene oxide (GO) nanoparticles into oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels. The hydrogels were characterized by AFM and electrochemistry workstation. A rat model of myocardial infarction was used to investigate the ability of OPF/GO to improve cardiac electrical propagation in the injured heart in vivo. Echocardiography (ECHO) was used to evaluate heart function 4 weeks after MI. Ca2+ imaging was used to visualize beating cardiomyocytes (CMs). Immunofluorescence staining was used to visualize the expression of cardiac-specific markers. Results: OPF/GO hydrogels had semiconductive properties that were lacking in pure OPF. In addition, the incorporation of GO into OPF hydrogels could improve cell attachment in vitro. Injection of OPF/GO 4 weeks after myocardial infarction in rats enhanced the Ca2+ signal conduction of cardiomyocytes in the infarcted region in comparison with PBS or OPF alone. Moreover, the injection of OPF/GO hydrogel into the infarct region enhanced the generation of cytoskeletal structure and intercalated disc assembly. Echocardiography analysis showed improvement in load-dependent ejection fraction/fractional shortening of heart function 4 weeks after injection. Conclusions: We prepared a conductive hydrogel (OPF/GO) that provide mechanical support and biological conduction in vitro and in vivo. We found that injected OPF/GO hydrogels can provide mechanical support and electric connection between healthy myocardium and the cardiomyocytes in the scar via activating the canonical Wnt signal pathway, thus upregulating the generation of Cx43 and gap junction associated proteins. Injection of OPF/GO hydrogel maintained better heart function after myocardial infarction than the injection of a nonconductive polymer.

Project description:BackgroundInjectable, acellular biomaterials hold promise to limit left ventricular remodeling and heart failure precipitated by infarction through bulking or stiffening the infarct region. A material with tunable properties (eg, mechanics, degradation) that can be delivered percutaneously has not yet been demonstrated. Catheter-deliverable soft hydrogels with in vivo stiffening to enhance therapeutic efficacy achieve these requirements.Methods and resultsWe developed a hyaluronic acid hydrogel that uses a tandem crosslinking approach, where the first crosslinking (guest-host) enabled injection and localized retention of a soft (<1 kPa) hydrogel. A second crosslinking reaction (dual-crosslinking) stiffened the hydrogel (41.4±4.3 kPa) after injection. Posterolateral infarcts were investigated in an ovine model (n≥6 per group), with injection of saline (myocardial infarction control), guest-host hydrogels, or dual-crosslinking hydrogels. Computational (day 1), histological (1 day, 8 weeks), morphological, and functional (0, 2, and 8 weeks) outcomes were evaluated. Finite-element modeling projected myofiber stress reduction (>50%; P<0.001) with dual-crosslinking but not guest-host injection. Remodeling, assessed by infarct thickness and left ventricular volume, was mitigated by hydrogel treatment. Ejection fraction was improved, relative to myocardial infarction at 8 weeks, with dual-crosslinking (37% improvement; P=0.014) and guest-host (15% improvement; P=0.058) treatments. Percutaneous delivery via endocardial injection was investigated with fluoroscopic and echocardiographic guidance, with delivery visualized by magnetic resonance imaging.ConclusionsA percutaneous delivered hydrogel system was developed, and hydrogels with increased stiffness were found to be most effective in ameliorating left ventricular remodeling and preserving function. Ultimately, engineered systems such as these have the potential to provide effective clinical options to limit remodeling in patients after infarction.

Dataset Information

Injectable Hydrogels Encapsulating Dual-Functional Au@Pt Core-Shell Nanoparticles Regulate Infarcted Microenvironments and Enhance the Therapeutic Efficacy of Stem Cells through Antioxidant and Electrical Integration.

Publications

Injectable Hydrogels Encapsulating Dual-Functional Au@Pt Core-Shell Nanoparticles Regulate Infarcted Microenvironments and Enhance the Therapeutic Efficacy of Stem Cells through Antioxidant and Electrical Integration.

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