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• Mesoporous silicon nanoparticles serve as carriers for encapsulating microRNA-29b mimics, which exhibit antifibrotic activity, subsequently coated with a complex of natural antioxidant tannic acid and zinc ions. • An injectable alginate hydrogel is engineered to locally deliver versatile nanoparticles exhibiting antioxidant and antifibrotic properties to the infarcted region of the heart. • Intramyocardial injection of this composite hydrogel inhibits cell apoptosis, enhances angiogenesis, and prevents myocardial fibrosis, thereby improving cardiac function post-myocardial infarction. Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac repair efficiency post-MI, culminating in adverse ventricular remodeling and potential heart failure. To address the diverse pathological stages of MI, an injectable composite hydrogel containing versatile nanoparticles was developed. In this study, mesoporous silicon nanoparticles (MSNs) served as carriers for encapsulating microRNA-29b (miR-29b) mimics with antifibrotic activity, subsequently coated with a complex of natural antioxidant tannic acid and zinc ions (TA/Zn). These nanoparticles were then embedded into a biocompatible alginate hydrogel to enhance retention within the infarcted myocardium. Upon injection into the infarcted region of MI mice, the composite hydrogel gradually released the nanoparticles as it degraded. Initially, the TA/Zn complex on the outer layer scavenged reactive oxygen species, thereby inhibiting cell apoptosis. The subsequent dissociation of the TA/Zn complex led to the release of the encapsulated miR-29b mimics that could inhibit the activation of cardiac fibroblasts and collagen production, thereby alleviating fibrosis progression. Overall, this composite hydrogel demonstrated the potential to reduce infarct size and improve cardiac function, suggesting its promise as a synergistic therapeutic approach for repairing infarcted myocardium. [Display omitted] [ABSTRACT FROM AUTHOR]

• An injectable alginate/fibrin hydrogel is developed to deliver cardiomyocytes and VEGF locally to the infarcted area of the heart. • This hydrogel supports the retention and integration of the transplanted cardiomyocytes into the host myocardium. • The delivered VEGF is favorable for blood recovery to improve the survival of cardiomyocytes. • Intramyocardial injection of this hydrogel promotes angiogenesis, inhibits fibrosis, and improves cardiac function after myocardial infarction. Myocardial infarction (MI) is one of the typical cardiovascular diseases, which persist as the leading cause of death globally. Due to the poor regenerative capability of endogenous cardiomyocytes (CMs), the transplantation of exogenous CMs becomes a promising option for MI treatment. However, the low retention and survival of transplanted cells still limit the clinical translation of cell therapy. Herein, an alginate/fibrin-based injectable hydrogel was prepared for the delivery of neonatal CMs and an angiogenesis agent vascular endothelial growth factor (VEGF) locally to the infarcted area of the heart. This hydrogel combined the specific advantages of alginate and fibrin with proper mechanical properties and cell affinity, showing good biocompatibility to support the retention and integration of the transplanted CMs to the host myocardium. Moreover, the delivered VEGF was favorable for the blood recovery to mitigate the ischemic microenvironment of the infarcted area and thus improved the survival of the transplanted CMs. Intramyocardial injection of this hydrogel to the infarcted area of the heart promoted angiogenesis, inhibited fibrosis, and improved cardiac function, exhibiting great potential for MI treatment. [ABSTRACT FROM AUTHOR]

Localized and sustained osteogenic-angiogenic stimulation to bone defects is critical for effective bone repair. Here, desferrioxamine (DFO) was loaded on silk fibroin nanofibers and blended with hydroxyapatite nanorods (HA), forming injectable DFO-loaded silk fibroin-HA nanocomposite hydrogels. The composite hydrogels remained homogeneous distribution of HA with high ratio (60 %) and also higher stiffness than that of pure silk fibroin nanofiber hydrogels, which provided stable osteogenic stimulation niches for tissue regeneration. Without the scarify of injectability, the hydrogels achieved slow delivery of DFO for above 60 days, resulting in suitable angiogenesis in vitro and in vivo and better osteogenesis than DFO-free systems. Compared to previous injectable silk fibroin-HA hydrogels, the introduction of vascularization capacity further stimulated the osteogenic differentiation of stem cells and accelerated new bone formation. Quicker and better bone healing were detected at defect sites after the injection of DFO-loaded nanocomposite hydrogels, indicating the effective synergistic effect of osteogenic and angiogenic cues. This work provides a simple and effective strategy of introducing angiogenic cues to bone matrices. We believe that the injectable nanocomposite hydrogels are suitable for the regeneration of bone tissues. [ABSTRACT FROM AUTHOR]