Dataset Information

Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization.

ABSTRACT: The controversy between polypyrrole's (Ppy) biocompatibility and its aggregation on nanofibers impedes application of conductive Ppy-incorporated nanofibers to create engineered cardiac microenvironments. The purpose of this study was to fabricate a functional scaffold for engineering cardiac patches (ECP) using a high concentration of methyl acrylic anhydride-gelatin (GelMA)-Ppy nanoparticles, mussel-inspired crosslinker, and electrospun (ES)-GelMA/polycaprolactone (PCL) nanofibrous membrane. Methods: First, spherical GelMA-Ppy nanoparticles were obtained when the methacrylate groups of GelMA formed a self-crosslinked network through oxidative polymerization of Ppy. Second, GelMA-Ppy nanoparticles were uniformly crosslinked on the ES-GelMA/PCL membrane through mussel-inspired dopamine-N'N'-methylene-bis-acrylamide (dopamine-MBA) crosslinker. Finally, the feasibility of the dopa-based conductive functional ECP scaffold was investigated in vitro and in vivo. Results: The GelMA-Ppy nanoparticles displayed excellent biocompatibility at a high concentration of 50 mg/mL. The massive GelMA-Ppy nanoparticles could be uniformly distributed on the ES nanofibers through dopamine-MBA crosslinker without obvious aggregation. The high concentration of GelMA-Ppy nanoparticles produced high conductivity of the dopamine-based (dopa-based) conductive membrane, which enhanced the function of cardiomyocytes (CMs) and yielded their synchronous contraction. GelMA-Ppy nanoparticles could also modify the topography of the pristine ES-GelMA/PCL membrane to promote vascularization in vitro. Following transplantation of the conductive membrane-derived ECP on the infarcted heart for 4 weeks, the infarct area was decreased by about 50%, the left ventricular shortening fraction percent (LVFS%) was increased by about 20%, and the neovascular density in the infarct area was significantly increased by about 9 times compared with that in the MI group. Conclusion: Our study reported a facile and effective approach to developing a functional ECP that was based on a mussel-inspired conductive nanofibrous membrane. This functional ECP could repair infarct myocardium through enhancing cardiac function and revascularization.

SUBMITTER: He Y

PROVIDER: S-EPMC6217052 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization.

He Yutong Y Ye Genlan G Song Chen C Li Chuangkun C Xiong Weirong W Yu Lei L Qiu Xiaozhong X Wang Leyu L

Theranostics 20181006 18

The controversy between polypyrrole's (Ppy) biocompatibility and its aggregation on nanofibers impedes application of conductive Ppy-incorporated nanofibers to create engineered cardiac microenvironments. The purpose of this study was to fabricate a functional scaffold for engineering cardiac patches (ECP) using a high concentration of methyl acrylic anhydride-gelatin (GelMA)-Ppy nanoparticles, mussel-inspired crosslinker, and electrospun (ES)-GelMA/polycaprolactone (PCL) nanofibrous membrane. < ...[more]

PMID: 30429892

Similar Datasets

Project description:Large skin wounds are one of the most important health problems in the world. Skin wound repair and tissue regeneration are complex processes involving many physiological signals, and effective wound healing remains an enormous clinical challenge. Therefore, there is an urgent need for a strategy to rapidly kill bacteria, promote cell proliferation and accelerate wound healing. At present, electrical stimulation (ES) is often used in the clinical treatment of skin wounds and can simulate the endogenous biological current of the body and accelerate the repair process of skin wounds. However, a single ES strategy has difficulty covering the entire wound area, which may lead to unsatisfactory therapeutic effects. To overcome this deficiency, it is essential to develop a collaborative treatment strategy that combines ES with other treatments. In this study, gold nanoparticles and antibacterial peptides (Os) were loaded on the surface of poly(lactic-co-glycolic acid) (PLGA) material through the reducibility and adhesion of polydopamine (PDA) and improved the electrical activity, anti-inflammatory, antibacterial and biocompatibility properties of the polymer material. At the same time, this composite membrane material (Os/Au-PDA@PLGA) combined with ES was used in wound therapy to improve the wound healing rate. The results show that the new wound repair material has good biocompatibility and can effectively promote cell proliferation and migration. Through the combined application of gold nanoparticles and antibacterial peptides Os, the polymer materials have more efficient bactericidal and antioxidant effects. The antibacterial experiment results showed that gold nanoparticles could further enhance the antibacterial activity of antibacterial peptides. Furthermore, the Os/Au-PDA@PLGA composite membrane has good hydrophilicity and electrical activity, which can provide a more favorable cell microenvironment for wound healing. In vivo studies using a full-thickness skin defect model in rats showed that the Os/Au-PDA@PLGA composite membrane had a better therapeutic effect than the pure PLGA material. More importantly, the combination of the Os/Au-PDA@PLGA composite with ES significantly accelerated the rate of vascularization and collagen deposition and promoted wound healing compared with non-ES controls. Therefore, the combination of the Au/Os-PDA@PLGA composite membrane with ES may provide a new strategy for the effective treatment of skin wounds.

Project description:Rationale and Objectives: Cellular therapies are hampered by poor survival and growth of grafts. We recently showed that the survival and repairing capacity of transplanted adult cells may be improved by co-expression of the anti-senescence telomerase reverse transcriptase (TERT) and anti-apoptotic myocardin (MYOCD). The current study aimed at testing whether forced co-expression of TERT and MYOCD improves post-infarct revascularization and tissue repair by adipose tissue-derived mesenchymal stromal cells (AT-MSCs). Methods: We transplanted AT-MSCs engineered to overexpress MYOCD and TERT in a murine model of acute myocardial infarction (AMI). We analyzed the immunoregulatory properties of AT-MSCs on post-AMI. We characterized in vitro and in vivo paracrine effects of AT-MSCs and their interactions with murine cardiospheres (CSps), all as parts of their reparative repertoire. Results: When transplanted into infarcted hearts of C57BL/6 mice, “rejuvenated” AT-MSCs overexpressing TERT and MYOCD (rAT-MSCs) decreased fibrosis and the intrafibrotic CD3 and B220 lymphocyte infiltration, and increased arteriolar density as well as ejection fraction compared with saline or mock-transduced AT-MSCs. These effects were accompanied by increased numbers of Ki-67+ and CD117+ cells, and the expression of cardiac actin and β-myosin heavy chain within the infarcted hearts. Both rAT-MSCs and their conditioned medium (CM) stimulated intracellular Ca2+ flux in CSps. CSp-derived cells had increased survival when preconditioned with CM or exosome-enriched fraction (Exo+) from rAT-MSCs and then exposed to simulated ischemia/reperfusion. Proteomic analysis of rAT-MSCs-Exo+ predicted the activation of vascular development and the inhibition of immune cell trafficking. Elevated concentration of miR-320a, miR-150-5p and miR-126-3p associated with regulation of apoptosis and vasculogenesis was confirmed in rAT-MSCs-Exo+. Conclusions: rAT-MSCs promote vasculogenesis and cell survival and reduce post-AMI inflammatory responses in a murine model of AMI. An integrated experimental and computational analysis revealed that Exo+ is the active component of the paracrine secretion by rAT-MSCs, with pro-angiogenic and pro-survival activities.

Project description:Myocardial infarction (MI) causes irreversible damage to the heart muscle, seriously threatening the lives of patients. Injectable hydrogels have attracted extensive attention in the treatment of MI. By promoting the coupling of mechanical and electrical signals between cardiomyocytes, combined with synergistic therapeutic strategies targeting the pathological processes of inflammation, proliferation, and fibrotic remodeling after MI, it is expected to improve the therapeutic effect. In this study, a pH/ROS dual-responsive injectable hydrogel was developed by modifying xanthan gum and gelatin with reversible imine bond and boronic ester bond double crosslinking. By encapsulating polydopamine-rosmarinic acid nanoparticles to achieve on-demand drug release in response to the microenvironment of MI, thereby exerting anti-inflammatory, anti-apoptotic, and anti-fibrosis effects. By adding conductive composites to improve the conductivity and mechanical strength of the hydrogel, restore electrical signal transmission in the infarct area, promote synchronous contraction of cardiomyocytes, avoid induced arrhythmias, and induce angiogenesis. Furthermore, the multifunctional hydrogel promoted the expression of cardiac-specific markers to restore cardiac function after MI. The in vivo and in vitro results demonstrate the effectiveness of this synergistic comprehensive treatment strategy in MI treatment, showing great application potential to promote the repair of infarcted hearts. Graphical abstract Image 1 Highlights • An injectable self-healing conductive hydrogel with pH/ROS dual-responsive drug release was prepared for the treatment of MI.• The OGDPR hydrogel has conductivity (6.27 × 10−4 S/cm) and elastic modulus (45.35 kPa) matching those of the natural heart.• The biocompatible hydrogel can resist oxidation, promote macrophage polarization and tube formation of endothelial cells.• The hydrogel can protect cardiac function, reduce arrhythmia susceptibility, and reduce infarct size and fibrosis after MI.• The hydrogel can reduce apoptosis and inflammation, and promote angiogenesis and the expression of cardiac-specific markers.

Dataset Information

Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization.

Publications

Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets