Dataset Information

Mussel-inspired conductive Ti2C-cryogel promotes functional maturation of cardiomyocytes and enhances repair of myocardial infarction.

ABSTRACT: Rationale: Researches on conductive engineering cardiac patch (ECP) for myocardial infarction (MI) treatment have achieved some progress in the animal while the availability of traditional conductive materials in ECP is still limited because of their controversial cytotoxicity. Here we aim to introduce a novel hydrophilic biocompatible conductive material: MXene Ti2C and mussel-inspired dopamine into PEGDA-GelMA cryogel to construct a bio-functional ECP of which the property closes to natural heart for the repair of MI. Method: MXene Ti2C was etched from MAX Ti2AlC, then uniformly dispersed into the prepolymer composed with dopamine-N', N'-methylene-bisacrylamide, methacrylate-gelatin, and poly (ethylene glycol) diacrylate by simple water bath sonication. The resilient conductive Ti2C-cryogel was fabricated by chemical cryogelation. The conductive ECP was evaluated in vitro and transplanted to the MI rat model for MI treatment. Results: In vitro, the 3D vessels-shape framework was observed in Ti2C-8-cryogel which was seeded with rats aortic endothelial cells. When the Ti2C-cryogels were cocultured with CMs, remarkably aligned sarcomere and the primitive intercalated disc between the mature CMs were formed on day 7. The as-prepared Ti2C-8-cryogel ECP also demonstrated rapid calcium transients and synchronous tissue-like beating. When transplanted into the infarcted heart of the MI rat model, the Ti2C-8-cryogel ECP could improve the cardiac function, reduce the infarct size, and inhibit the inflammatory response. Obvious vasculation especially newly formed arteriole was also found. Conclusion: A novel conductive Ti2C-embedded cardiac patch with suitable conductivity and the mechanical property was developed and could be served as an ideal candidate for MI repair.

SUBMITTER: Ye G

PROVIDER: S-EPMC7019164 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Mussel-inspired conductive Ti2C-cryogel promotes functional maturation of cardiomyocytes and enhances repair of myocardial infarction.

Ye Genlan G Wen Zubiao Z Wen Feng F Song Xiaoping X Wang Leyu L Li Chuangkun C He Yutong Y Prakash Sugandha S Qiu Xiaozhong X

Theranostics 20200112 5

Rationale: Researches on conductive engineering cardiac patch (ECP) for myocardial infarction (MI) treatment have achieved some progress in the animal while the availability of traditional conductive materials in ECP is still limited because of their controversial cytotoxicity. Here we aim to introduce a novel hydrophilic biocompatible conductive material: MXene Ti2C and mussel-inspired dopamine into PEGDA-GelMA cryogel to construct a bio-functional ECP of which the property cl ...[more]

PMID: 32104499

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Project description: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.

Project description:Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×10(6) or 1x10(6) cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×10(6) CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved cardiac function with a direct contraction effect and enhanced angiogenesis.

Dataset Information

Mussel-inspired conductive Ti2C-cryogel promotes functional maturation of cardiomyocytes and enhances repair of myocardial infarction.

Publications

Mussel-inspired conductive Ti<sub>2</sub>C-cryogel promotes functional maturation of cardiomyocytes and enhances repair of myocardial infarction.

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