Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.

Acute myocardial infarction (MI) is the leading cause of death worldwide. Exogenous delivery of nitric oxide (NO) to the infarcted myocardium has proven to be an effective strategy for treating MI due to the multiple physiological functions of NO. However, reperfusion of blood flow to the ischemic tissues is accompanied by the overproduction of toxic reactive oxygen species (ROS), which can further exacerbate tissue damage and compromise the therapeutic efficacy. Here, an injectable hydrogel is synthesized from the chitosan modified by boronate-protected diazeniumdiolate (CS-B-NO) that can release NO in response to ROS stimulation and thereby modulate ROS/NO disequilibrium after ischemia/reperfusion (I/R) injury. Furthermore, administration of CS-B-NO efficiently attenuated cardiac damage and adverse cardiac remodeling, promoted repair of the heart, and ameliorated cardiac function, unlike a hydrogel that only released NO, in a mouse model of myocardial I/R injury. Mechanistically, regulation of the ROS/NO balance activated the antioxidant defense system and protected against oxidative stress induced by I/R injury via adaptive regulation of the Nrf2-Keap1 pathway. Inflammation is then reduced by inhibition of the activation of NF-𝜿B signaling. Collectively, these results show that this dual-function hydrogel may be a promising candidate for the protection of tissues and organs after I/R injury.

Restoration of sufficient blood supply for the treatment of ischemia remains a significant scientific and clinical challenge. Here, a cell‐like nanoparticle delivery technology is introduced that is capable of recapitulating multiple cell functions for the spatiotemporal triggering of vascular regeneration. Specifically, a copper‐containing protein is successfully prepared using a recombinant protein scaffold based on a de novo design strategy, which facilitates the timely release of nitric oxide and improved accumulation of particles within ischemic tissues. Through closely mimicking physiological cues, the authors demonstrate the benefits of bioactive factors secreted from hypoxic stem cells on promoting angiogenesis. Following this cell‐mimicking manner, artificial hybrid nanosized cells (Hynocell) are constructed by integrating the hypoxic stem cell secretome into nanoparticles with surface coatings of cell membranes fused with copper‐containing protein. The Hynocell, hybridized with different cell‐derived components, provides synergistic effects on targeting ischemic tissues and promoting vascular regeneration in acute hindlimb ischemia and acute myocardial infarction models. This study offers new insights into the utilization of nanotechnology to potentiate the development of cell‐free therapeutics.

We report a mitochondria-targeted and superoxide-responsive nitric oxide donor with good protection against ischemia/reperfusion injury in H9c2 cells and isolated rat hearts.

Designing hydrogel-based constructs capable of adjusting immune cell functions holds promise for skin tissue regeneration. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have attracted increasing attention owing to their anti-inflammatory and proangiogenic effects. Herein, we constructed a biofunctional hydrogel in which MSC-derived sEVs were incorporated into the injectable hyaluronic acid (HA) hydrogel, thus endowing the hydrogel with immunomodulatory effects. When implanted onto the wound site in a mouse large skin injury model, this functional hydrogel facilitates wound healing and inhibits scar tissue formation by driving macrophages towards an anti-inflammatory and anti-fibrotic (M2c) phenotype. Further investigation showed that the M2c-like phenotype induced by MSC-derived sEVs markedly inhibited the activation of fibroblasts, which could result in scarless skin wound healing. Taken together, these results suggest that modulation of the immune response is a promising and efficient approach to prevent fibrotic scar formation.

Representative volume elements of syntactic foams with a random filling of short glass fibers and hollow glass microspheres in epoxy resin were established by a random sequential adsorption method. The fiber volume fraction was set at 4%, and the microsphere volume fraction range was from 5 to 30%. This numerical simulation was studied with ANSYS software. The influence on the elastic and plastic mechanical properties of syntactic foams of the microsphere volume fraction and relative wall thickness were investigated, and the plastic strain evolution process in the composites was analyzed. The results show that the compressive yield limit and Young's modulus values of the syntactic foams decreased with increasing microsphere volume fraction when the microsphere relative wall thickness was 0.02, but these properties were enhanced with increasing microsphere volume fraction when the relative wall thickness exceeded 0.04. The specific strength and tangent modulus values of the composites increased with increasing microsphere volume fraction. In addition, we observed that the yield stress, Young's modulus, and tangent modulus values of the syntactic foams were obviously enhanced by the addition of glass fibers. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44188.

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