An Intrinsically Magnetic Epicardial Patch for Rapid Vascular Reconstruction and Drug Delivery.

Myocardial infarction (MI) is a major cause of mortality worldwide. The major limitation of regenerative therapy for MI is poor cardiac retention of therapeutics, which results from an inefficient vascular network and poor targeting ability. In this study, a two-layer intrinsically magnetic epicardial patch (MagPatch) prepared by 3D printing with biocompatible materials like poly (glycerol sebacate) (PGS) is designed, poly (ε-caprolactone) (PCL), and NdFeB. The two-layer structure ensured that the MagPatch multifariously utilized the magnetic force for rapid vascular reconstruction and targeted drug delivery. MagPatch accumulates superparamagnetic iron oxide (SPION)-labelled endothelial cells, instantly forming a ready-implanted organization, and rapidly reconstructs a vascular network anastomosed with the host. In addition, the prefabricated vascular network within the MagPatch allowed for the efficient accumulation of SPION-labelled therapeutics, amplifying the therapeutic effects of cardiac repair. This study defined an extendable therapeutic platform for vascularization-based targeted drug delivery that is expected to assist in the progress of regenerative therapies in clinical applications.

Self-healing polyurethane-elastomer with mechanical tunability for multiple biomedical applications in vivo.

The unique properties of self-healing materials hold great potential in the field of biomedical engineering. Although previous studies have focused on the design and synthesis of self-healing materials, their application in in vivo settings remains limited. Here, we design a series of biodegradable and biocompatible self-healing elastomers (SHEs) with tunable mechanical properties, and apply them to various disease models in vivo, in order to test their reparative potential in multiple tissues and at physiological conditions. We validate the effectiveness of SHEs as promising therapies for aortic aneurysm, nerve coaptation and bone immobilization in three animal models. The data presented here support the translation potential of SHEs in diverse settings, and pave the way for the development of self-healing materials in clinical contexts.

A perfusable, multifunctional epicardial device improves cardiac function and tissue repair.

Despite advances in technologies for cardiac repair after myocardial infarction (MI), new integrated therapeutic approaches still need to be developed. In this study, we designed a perfusable, multifunctional epicardial device (PerMed) consisting of a biodegradable elastic patch (BEP), permeable hierarchical microchannel networks (PHMs) and a system to enable delivery of therapeutic agents from a subcutaneously implanted pump. After its implantation into the epicardium, the BEP is designed to provide mechanical cues for ventricular remodeling, and the PHMs are designed to facilitate angiogenesis and allow for infiltration of reparative cells. In a rat model of MI, implantation of the PerMed improved ventricular function. When connected to a pump, the PerMed enabled targeted, sustained and stable release of platelet-derived growth factor-BB, amplifying the efficacy of cardiac repair as compared to the device without a pump. We also demonstrated the feasibility of minimally invasive surgical PerMed implantation in pigs, demonstrating its promise for clinical translation to treat heart disease.

Injectable Citrate-Based Hydrogel as an Angiogenic Biomaterial Improves Cardiac Repair after Myocardial Infarction.

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.

Elastic 3D-Printed Hybrid Polymeric Scaffold Improves Cardiac Remodeling after Myocardial Infarction.

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.