Effects of cerium oxide nanoparticles on the growth of keratinocytes, fibroblasts and vascular endothelial cells in cutaneous wound healing.

Rapid and effective wound healing requires a coordinated cellular response involving fibroblasts, keratinocytes and vascular endothelial cells (VECs). Impaired wound healing can result in multiple adverse health outcomes and, although antibiotics can forestall infection, treatments that accelerate wound healing are lacking. We now report that topical application of water soluble cerium oxide nanoparticles (Nanoceria) accelerates the healing of full-thickness dermal wounds in mice by a mechanism that involves enhancement of the proliferation and migration of fibroblasts, keratinocytes and VECs. The Nanoceria penetrated into the wound tissue and reduced oxidative damage to cellular membranes and proteins, suggesting a therapeutic potential for topical treatment of wounds with antioxidant nanoparticles.

[1]  R. Lenk,et al.  A novel class of compounds with cutaneous wound healing properties. , 2010, Journal of biomedical nanotechnology.

[2]  H. Esterbauer,et al.  Monoclonal antibodies for detection of 4-hydroxynonenal modified proteins. , 1996, Free radical research.

[3]  Amit Kumar,et al.  Cerium oxide nanoparticles scavenge nitric oxide radical (˙NO). , 2012, Chemical communications.

[4]  R. Narayan,et al.  Nanoceria as antioxidant: Synthesis and biomedical applications , 2008, JOM.

[5]  Tarynn M Witten,et al.  Impaired wound healing. , 2007, Clinics in dermatology.

[6]  M. Mattson,et al.  A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice , 2010, PloS one.

[7]  B. Brachvogel,et al.  Regulation of angiogenesis: wound healing as a model. , 2007, Progress in histochemistry and cytochemistry.

[8]  R. Swerlick,et al.  HMEC-1: establishment of an immortalized human microvascular endothelial cell line. , 1992, The Journal of investigative dermatology.

[9]  Ashutosh Kumar Singh,et al.  Enhancement of wound healing by curcumin in animals , 1998, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[10]  R. Sivamani,et al.  Antioxidant Therapies for Wound Healing: A Clinical Guide to Currently Commercially Available Products , 2011, Skin Pharmacology and Physiology.

[11]  Amit Kumar,et al.  The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. , 2012, Biomaterials.

[12]  Sudipta Seal,et al.  Anti-inflammatory properties of cerium oxide nanoparticles. , 2009, Small.

[13]  K. Pehr,et al.  Why don't we use vitamin E in dermatology? , 1993, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[14]  Sudipta Seal,et al.  The role of cerium redox state in the SOD mimetic activity of nanoceria. , 2008, Biomaterials.

[15]  P. Pelicci,et al.  The Redox Enzyme p66Shc Contributes to Diabetes and Ischemia-Induced Delay in Cutaneous Wound Healing , 2010, Diabetes.

[16]  M. Mattson,et al.  Numb Endocytic Adapter Proteins Regulate the Transport and Processing of the Amyloid Precursor Protein in an Isoform-dependent Manner , 2008, Journal of Biological Chemistry.

[17]  J. Varani,et al.  Pretreatment of diabetic rats with lipoic acid improves healing of subsequently-induced abrasion wounds , 2005, Archives of Dermatological Research.

[18]  Olivera Stojadinovic,et al.  PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[19]  Alexander M Seifalian,et al.  Nanosilver as a new generation of nanoproduct in biomedical applications. , 2010, Trends in biotechnology.

[20]  Dan Yang,et al.  Direct Evidence for Hydroxyl Radical Scavenging Activity of Cerium Oxide Nanoparticles , 2011 .

[21]  S. Seal,et al.  Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides , 2006, Nature nanotechnology.

[22]  Paul Martin,et al.  Inflammatory cells during wound repair: the good, the bad and the ugly. , 2005, Trends in cell biology.

[23]  Sudipta Seal,et al.  Sustained protection against photoreceptor degeneration in tubby mice by intravitreal injection of nanoceria. , 2012, Biomaterials.

[24]  S. Seal,et al.  Redox-active radical scavenging nanomaterials. , 2010, Chemical Society reviews.

[25]  R. Tarnuzzer,et al.  Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. , 2005, Nano letters.

[26]  S. Seal,et al.  Nanoceria extend photoreceptor cell lifespan in tubby mice by modulation of apoptosis/survival signaling pathways , 2011, Neurobiology of Disease.

[27]  M. Das,et al.  Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. , 2007, Biomaterials.

[28]  A. Shukla,et al.  Antioxidant status in delayed healing type of wounds , 2000, International journal of experimental pathology.

[29]  S. Seal,et al.  Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. , 2007, Chemical communications.

[30]  Amit Kumar,et al.  Unveiling the mechanism of uptake and sub-cellular distribution of cerium oxide nanoparticles. , 2010, Molecular bioSystems.

[31]  Matthias Schäfer,et al.  Oxidative stress in normal and impaired wound repair. , 2008, Pharmacological research.

[32]  S. Seal,et al.  Nanoceria exhibit redox state-dependent catalase mimetic activity. , 2010, Chemical communications.