Angiogenesis is a crucial biological process of development of blood vessels from pre-existing vasculature, which helps in several physiological functions including embryonic development, hair growth, ovulation, menstruation, tissue repair, and regeneration. Contrastingly, it is also imperative in various pathological conditions like cardiovascular/ischemic diseases, rheumatoid arthritis, cancers, ocular/retinal diseases, and others. These disease conditions are often treated by manipulating angiogenesis using different pro-angiogenic or antiangiogenic factors/molecules through either promoting or inhibiting this complex process, respectively. However, these conventional angiogenic treatment strategies fall short in attaining the desired therapeutic effect due to several limitations including low bioavailability, rapid clearance, high cost, nonspecificity, drug resistance and side effects. Therefore, it is high time for the advancement of different pro- and antiangiogenic materials that could overcome aforesaid limitations, followed by their effective use for the therapy of angiogenesis related diseases. Recently, nanotechnology has drastically advanced in various areas of biology and medicine including therapeutic angiogenesis. Globally, many research groups including ours explored various inorganic metal nanomaterials that could efficiently manipulate the angiogenesis process either by augmenting or inhibiting it. The extensive investigation of the mechanisms underlying nanomaterials-mediated manipulation of angiogenesis is also well-documented. In the present review article, we intend to introduce the recent developments of inorganic nanomedicine manipulating angiogenesis with major focus on pro-angiogenic nanomaterials and their therapeutic applications along with associated challenges and future directions.
Critical limb ischemia (CLI) is a severe type of peripheral artery disease (PAD) which occurs due to an inadequate supply of blood to the limb extremities. Patients with CLI often suffer from extreme cramping pain, impaired wound healing, immobility, cardiovascular complications, amputation of the affected limb and even death. The conventional therapy for treating CLI includes surgical revascularization as well as restoration of angiogenesis using growth factor therapy. However, surgical revascularization is only suitable for a small percentage of CLI patients and is associated with a high perioperative mortality rate. The use of growth factors is also limited in terms of their poor therapeutic angiogenic potential, as observed in earlier clinical studies which could be attributed to their poor bio-availability and non-specificity issues. Therefore, to overcome the aforesaid disadvantages of conventional strategies there is an urgent need for the advancement of new alternative therapeutic biomaterials to treat CLI. In the past few decades, various research groups, including ours, have been involved in developing different pro-angiogenic nanomaterials. Among these, zinc oxide nanoflowers (ZONFs), established in our laboratory, are considered one of the more potent nanoparticles for inducing therapeutic angiogenesis. In our earlier studies we showed that ZONFs promote angiogenesis by inducing the formation of reactive oxygen species and nitric oxide (NO) as well as activating Akt/MAPK/eNOS cell signaling pathways in endothelial cells. Recently, we have also reported the therapeutic potential of ZONFs to treat cerebral ischemia through their neuritogenic and neuroprotective properties, exploiting angio-neural cross-talk. Considering the excellent pro-angiogenic properties of ZONFs and the importance of revascularization for the treatment of CLI, in the present study we comprehensively explore the therapeutic potential of ZONFs in a rat hind limb ischemia model (established by ligating the hind limb femoral artery), an animal model that mimics CLI in humans. The behavioral studies, laser Doppler perfusion imaging, histopathology and immunofluorescence as well as estimation of serum NO level showed that the administration of ZONFs could ameliorate ischemia in rats at a faster rate by promoting therapeutic angiogenesis to the ischemic sites. Altogether, the present study offers an alternative nanomedicine approach employing ZONFs for the treatment of PADs.
Functionalized cerium oxide nanoparticles (CeNPs) loaded fibro-porous Poly-L-Lactic acid (PLLA)/Gelatin composite membranes were prepared via electrospinning technology. Considering the importance of such membrane scaffolds for promoting angiogenesis in tissue engineering...
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