Single dose of intravenous miR199a-5p delivery targeting ischemic heart for long-term repair of myocardial infarction.

Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and uncertain outcomes pose obstacles. microRNAs regulate genes involved in apoptosis, angiogenesis, and myocardial contraction, making them valuable for long-term repair. In this study, we find downregulated miR-199a-5p expression in MI. Intramyocardial injection of miR-199a-5p into the infarcted region of male rats revealed its dual protective effects on the heart. Specifically, miR-199a-5p targets AGTR1, diminishing early oxidative damage post-myocardial infarction, and MARK4, which influences long-term myocardial contractility and enhances cardiac function. To deliver miR-199a-5p efficiently and specifically to ischemic myocardial tissue, we use CSTSMLKAC peptide to construct P-MSN/miR199a-5p nanoparticles. Intravenous administration of these nanoparticles reduces myocardial injury and protects cardiac function. Our findings demonstrate the effectiveness of P-MSN/miR199a-5p nanoparticles in repairing MI through enhanced contraction and anti-apoptosis. miR199a-5p holds significant therapeutic potential for long-term repair of myocardial infarction.

Flexible Conductive Decellularized Fish Skin Matrix as a Functional Scaffold for Myocardial Infarction Repair.

Engineering cardiac patches are proven to be effective in myocardial infarction (MI) repair, but it is still a tricky problem in tissue engineering to construct a scaffold with good biocompatibility, suitable mechanical properties, and solid structure. Herein, decellularized fish skin matrix is utilized with good biocompatibility to prepare a flexible conductive cardiac patch through polymerization of polydopamine (PDA) and polypyrrole (PPy). Compared with single modification, the double modification strategy facilitated the efficiency of pyrrole polymerization, so that the patch conductivity is improved. According to the results of experiments in vivo and in vitro, the scaffold can promote the maturation and functionalization of cardiomyocytes (CMs). It can also reduce the inflammatory response, increase local microcirculation, and reconstruct the conductive microenvironment in infarcted myocardia, thus improving the cardiac function of MI rats. In addition, the excellent flexibility of the scaffold, which enables it to be implanted in vivo through "folding-delivering-re-stretehing" pathway, provides the possibility of microoperation under endoscope, which avoids the secondary damage to myocardium by traditional thoracotomy for implantation surgery.

An injectable elastic hydrogel crosslinked with curcumin-gelatin nanoparticles as a multifunctional dressing for the rapid repair of bacterially infected wounds.

Injectable self-healing hydrogel dressings with excellent elasticity and multifunctional repair effects have been in high demand in wound healing applications, while maintaining stable elasticity in injectable multifunctional hydrogel dressings is still a challenge. Based on carboxymethyl chitosan (CMCS), curcumin-gelatin nanoparticles (CG NPs), and sodium alginate oxide (OSA), we developed a double-crosslinking injectable elastic self-healing hydrogel without any chemical cross-linking agent as a multifunctional wound healing dressing. CG NPs were more stable than pure curcumin (Cur) nanoparticles and could regulate the cross-linking of injectable hydrogels for high elasticity and rapid self-healing. We found that the CG NPs endowed the injectable hydrogel with good anti-inflammatory, antibacterial, and reactive oxygen scavenging activities and could significantly shorten the wound healing time in infected full-thickness skin defect rats by promoting the polarization of M2-type macrophages, reducing oxidative damage, accelerating collagen deposition, enhancing granulation formation, and elevating angiogenesis. Taken together, the tunable elastic injectable hydrogel dressing exhibited a long-term service life with sustained repair function and can be taken as an optimal candidate for bacteria-infected wound healing.

A smart adhesive Janus hydrogel for non-invasive cardiac repair and tissue adhesion prevention.

Multifunctional hydrogel with asymmetric and reversible adhesion characteristics is essential to handle the obstructions towards bioapplications of trauma removal and postoperative tissue synechia. Herein, we developed a responsively reversible and asymmetrically adhesive Janus hydrogel that enables on-demand stimuli-triggered detachment for efficient myocardial infarction (MI) repair, and synchronously prevents tissue synechia and inflammatory intrusion after surgery. In contrast with most irreversibly and hard-to-removable adhesives, this Janus hydrogel exhibited a reversible adhesion capability and can be noninvasively detached on-demand just by slight biologics. It is interesting that the adhesion behaves exhibited a molecularly encoded adhesion-adaptive stiffening feature similar to the self-protective stress-strain effect of biological tissues. In vitro and in vivo experiments demonstrated that Janus hydrogel can promote the maturation and functions of cardiomyocytes, and facilitate MI repair by reducing oxidative damage and inflammatory response, reconstructing electrical conduction and blood supply in infarcted area. Furthermore, no secondary injury and tissue synechia were triggered after transplantation of Janus hydrogel. This smart Janus hydrogel reported herein offers a potential strategy for clinically transformable cardiac patch and anti-postoperative tissue synechia barrier.

Elastic and Conductive Melanin/Poly(Vinyl Alcohol) Composite Hydrogel for Enhancing Repair Effect on Myocardial Infarction.

Heart failure caused by acute myocardial infarction (MI) still remains the main cause of death worldwide. Development of conductive hydrogels provided a promising approach for the treatment of myocardial infarction. However, the therapeutic potential of these hydrogels is still limited by material toxicity or low conductivity. The latter directly affects the coupling and the propagation of electrical signals between cells. Here, a functional conductive hydrogel by combining hydrophilic and biocompatible poly(vinyl alcohol) (PVA) with conductive melanin nanoparticles under physical crosslinking conditions is prepared. The composite hydrogels prepared by a facile fabrication process of five freeze/thaw cycles possessed satisfying mechanical properties and conductivity close to those of the natural heart. The physical properties and biocompatibility are evaluated in vitro experiments, showing that the introduction of melanin particles successfully improved the elasticity, conductivity, and cell adhesion of PVA hydrogel. In vivo, the composite hydrogels can enhance the cardiac repair effect by reducing MI area, slowing down ventricular wall thinning, and promoting the vascularization of infarct area in MI rat model. It is believed that the melanin/PVA composite hydrogel may be a suitable candidate material for MI repair.