Nonhealing diabetic wounds are common complications for diabetic patients. Because chronic hypoxia prominently delays wound healing, sustained oxygenation to alleviate hypoxia is hypothesized to promote diabetic wound healing. However, sustained oxygenation cannot be achieved by current clinical approaches, including hyperbaric oxygen therapy. Here, we present a sustained oxygenation system consisting of oxygen-release microspheres and a reactive oxygen species (ROS)–scavenging hydrogel. The hydrogel captures the naturally elevated ROS in diabetic wounds, which may be further elevated by the oxygen released from the administered microspheres. The sustained release of oxygen augmented the survival and migration of keratinocytes and dermal fibroblasts, promoted angiogenic growth factor expression and angiogenesis in diabetic wounds, and decreased the proinflammatory cytokine expression. These effects significantly increased the wound closure rate. Our findings demonstrate that sustained oxygenation alone, without using drugs, can heal diabetic wounds.
Nanoparticle-based drug delivery system (DDS) is considered promising for cancer treatment. Compared with traditional DDS, the nanoparticle-based DDS shows improved efficacy by: 1) increasing half-life of vulnerable drugs and proteins, 2) improving the solubility of hydrophobic drugs, and 3) allowing controlled and targeted release of drugs in diseased site. This review mainly focuses on nanoparticle-based DDS fabricated from chitosan, silica, and poly (lactic-co-glycolic acid). Their fabrication methods and applications in cancer treatment are introduced. The current limitations and future perspectives of the nanoparticle-based DDS are discussed.
Oxygen deficiency after myocardial infarction (MI) leads to massive cardiac cell death. Protection of cardiac cells and promotion of cardiac repair are key therapeutic goals. These goals may be achieved by re-introducing oxygen into the infarcted area. Yet current systemic oxygen delivery approaches cannot efficiently diffuse oxygen into the infarcted area that has extremely low blood flow. In this work, we developed a new oxygen delivery system that can be delivered specifically to the infarcted tissue, and continuously release oxygen to protect the cardiac cells. The system was based on a thermosensitive, injectable and fast gelation hydrogel, and oxygen releasing microspheres. The fast gelation hydrogel was used to increase microsphere retention in the heart tissue. The system was able to continuously release oxygen for 4 weeks. The released oxygen significantly increased survival of cardiac cells under the hypoxic condition (1% O2) mimicking that of the infarcted hearts. It also reduced myofibroblast formation under hypoxic condition (1% O2). After implanting into infarcted hearts for 4 weeks, the released oxygen significantly augmented cell survival, decreased macrophage density, reduced collagen deposition and myofibroblast density, and stimulated tissue angiogenesis, leading to a significant increase in cardiac function.
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