Three-dimensional (3D) printing thermosets offers great potential to customize sophisticated constructs for a myriad of applications.

In conclusion, these findings reveal a pivotal role for miR-532-prss23 axis in regulating CEC function after MI, and this novel axis could be suitable for therapeutic intervention in ischemic heart disease.

Myocardial remodeling, including ventricular dilation and wall thinning, is an important pathological process caused by myocardial infarction (MI). To intervene in this pathological process, a new type of cardiac scaffold composed of a thermoset (poly‐[glycerol sebacate], PGS) and a thermoplastic (poly‐[ε‐caprolactone], PCL) is directly printed by employing fused deposition modeling 3D‐printing technology. The PGS‐PCL scaffold possesses stacked construction with regular crisscrossed filaments and interconnected micropores and exhibits superior mechanical properties. In vitro studies demonstrate favorable biodegradability and biocompatibility of the PGS‐PCL scaffold. When implanted onto the infarcted myocardium, this scaffold improves and preserves heart function. Furthermore, the scaffold improves several vital aspects of myocardial remodeling. On the morphological level, the scaffold reduces ventricular wall thinning and attenuated infarct size, and on the cellular level, it enhances vascular density and increases M2 macrophage infiltration, which might further contribute to the mitigated myocardial apoptosis rate. Moreover, the flexible PGS‐PCL scaffold can be tailored to any desired shape, showing promise for annular‐shaped restraint device application and meeting the demands for minimal invasive operation. Overall, this study demonstrates the therapeutic effects and versatile applications of a novel 3D‐printed, biodegradable and biocompatible cardiac scaffold, which represents a promising strategy for improving myocardial remodeling after MI.

Implanted medical biomaterials are closely in contact with host biological systems via biomaterial–cell/tissue interactions, and these interactions play pivotal roles in regulating cell functions and tissue regeneration. However, many biomaterials degrade over time, and these degradation products also have been shown to interact with host cells/tissue. Therefore, it may prove useful to specifically design implanted biomaterials with degradation products which greatly improve the performance of the implant. Herein, we report an injectable, citrate-containing polyester hydrogel which can release citrate as a cell regulator via hydrogel degradation and simultaneously show sustained release of an encapsulated growth factor Mydgf. By coupling the therapeutic effect of the hydrogel degradation product (citrate) with encapsulated Mydgf, we observed improved postmyocardial infarction (MI) heart repair in a rat MI model. Intramyocardial injection of our Mydgf-loaded citrate-containing hydrogel was shown to significantly reduce scar formation and infarct size, increase wall thickness and neovascularization, and improve heart function. This bioactive injectable hydrogel-mediated combinatorial approach offers myriad advantages including potential adjustment of delivery rate and duration, improved therapeutic effect, and minimally invasive administration. Our rational design combining beneficial degradation product and controlled release of therapeutics provides inspiration toward the next generation of biomaterials aiming to revolutionize regenerative medicine.

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The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic- co -glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (NP-liraglutide) on experimental MI. PLGA–PEG nanoparticles (NPs) have been shown to efficiently load liraglutide and release bioactive liraglutide in a sustained manner. For in vitro test, the released liraglutide retained bioactivity, as measured by its ability to activate liraglutide signaling pathways. Next, we compared the effects of an intramyocardial injection of saline, empty NPs, free liraglutide and NP-liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4 weeks. More importantly, an intramyocardial injection of NP-liraglutide was sufficient to improve cardiac function ( P <0.05), attenuate the infarct size ( P <0.05), preserve wall thickness ( P <0.05), promote angiogenesis ( P <0.05) and prevent cardiomyocyte apoptosis ( P <0.05) at 4 weeks after injection without affecting glucose levels. The local, controlled, intramyocardial delivery of NP-liraglutide represents an effective and promising strategy for the treatment of MI.

Newborns with critical congenital heart disease are at significant risk of developing heart failure later in life. Because treatment options for end-stage heart disease in children are limited, regenerative therapies for these patients would be of significant benefit. During neonatal cardiac surgery, a portion of the thymus is removed and discarded. This discarded thymus tissue is a good source of MSCs that we have previously shown to be proangiogenic and to promote cardiac function in an in vitro model of heart tissue. The purpose of this study was to further evaluate the cardiac regenerative and protective properties of neonatal thymus (nt) MSCs. We found that ntMSCs expressed and secreted the proangiogenic and cardiac regenerative morphogen sonic hedgehog (Shh) in vitro more than patient-matched bone-derived MSCs. We also found that organoid culture of ntMSCs stimulated Shh expression. We then determined that ntMSCs were cytoprotective of neonatal rat cardiomyocytes exposed to H2O2. Finally, in a rat left coronary ligation model, we found that scaffoldless cell sheet made of ntMSCs applied to the LV epicardium immediately after left coronary ligation improved LV function, increased vascular density, decreased scar size, and decreased cardiomyocyte death four weeks after infarction. We conclude that ntMSCs have cardiac regenerative properties and warrant further consideration as a cell therapy for congenital heart disease patients with heart failure.