najoNanosystems: Physics, Chemistry, MathematicsНаносистемы: физика, химия, математика2220-80542305-7971Университет ИТМО10.17586/2220-8054-2020-11-4-453-461najo-414Research ArticleCHEMISTRY AND MATERIALS SCIENCEХИМИЯ И НАУКА О МАТЕРИАЛАХComparative evaluation for wound healing potentials of bulk and nano forms of zinc oxide ointmentGuptaV.vijayta1gupta@gmail.comVermaP. K.

SKUAST-Jammu, J&K

GuptaA.

J&K

KantV.

IVRI, Bareilly, UP

KumarP.

IVRI, Bareilly, UP

SharmaM.Department of Chemistry, University of JammuIndiaDivision of Pharmacology & ToxicologyIndiaDepartment of Physics, University of JammuIndiaDepartment of PathologyIndia202029072025114453–461Copyright © Gupta V., Verma P.K., Gupta A., Kant V., Kumar P., Sharma M., 20252025Gupta V., Verma P.K., Gupta A., Kant V., Kumar P., Sharma M.Gupta V., Verma P.K., Gupta A., Kant V., Kumar P., Sharma M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nanojournal.ifmo.ru/jour/article/view/414

Development of nanotechnology has led to massive breakthroughs in the area of wound healing. Recently, metal oxide nanoparticles have shown a broad range of applications in biomedical fields. The lack of potent healing agents for complicated wounds and healing potentials of zinc oxide (ZnO) motivated us to evaluate the wound healing potentials of nano ZnO in comparison to its bulk form in rats. In the present study, single open excision wounds (2×2 cm2) were created on the backs of fifteen rats and divided into Group I, II and III. On the wounds of group I, II and III, topical application of ointment base, bulk ZnO (20 %) and ZnO nanoparticles (2 %) was done for 14 days, respectively. Significantly smaller wound area and increased percent wound contraction was evident in the ZnO nanoparticles-treated group. Histopathological analysis revealed that the ZnO nanoparticle-treated wounds possessed reduced numbers of fibroblasts and blood vessels. However, collagen fibers in ZnO treated group were compactly arranged in thick bundles with a well-organized manner and orientation. The newly formed epithelial layer was also covering more area of healing tissue in the ZnO nanoparticle-treated group. The ZnO nanoparticle-treated group also revealed the higher overall wound maturity score, as compared to other groups. In view of this, it might be concluded that topical application of ZnO nanoparticles (2 %) caused faster wound healing and the healing was better than bulk ZnO treatment, even at ten-fold lower concentration.

Zinc oxidenanoparticleswound healingcollagenepithelial layerratsReferencesBello D., Martin J., et al. Physicochemical and morphological characterisation of nanoparticles from photocopiers: implications for environmental health. Nanotoxicology, 2012, 7 (5), P. 989–1003.Bello D., Martin J., et al. Physicochemical and morphological characterisation of nanoparticles from photocopiers: implications for environmental health. Nanotoxicology, 2012, 7 (5), P. 989–1003.Demokritou P., Gass S., et al. An in vivo and in vitro toxicological characterisation of realistic nanoscale CeO2 inhalation exposures. Nanotoxicology, 2013, 7 (8), P. 1338–1350.Demokritou P., Gass S., et al. An in vivo and in vitro toxicological characterisation of realistic nanoscale CeO2 inhalation exposures. Nanotoxicology, 2013, 7 (8), P. 1338–1350.Pirela S., Molina R., et al. Effects of copy center particles on the lungs: a toxicological characterization using a Balb/c mouse model. Inhal. Toxicol., 2013, 25 (9), P. 498–508.Pirela S., Molina R., et al. Effects of copy center particles on the lungs: a toxicological characterization using a Balb/c mouse model. Inhal. Toxicol., 2013, 25 (9), P. 498–508.Larsen S.T., Roursgaard M., Jensen K.A., Nielsen G.D. Nano titanium dioxide particles promote allergic sensitization and lung inflammation in mice. Basic Clin. Pharmacol. Toxicol., 2010, 106 (2), P. 114–117.Larsen S.T., Roursgaard M., Jensen K.A., Nielsen G.D. Nano titanium dioxide particles promote allergic sensitization and lung inflammation in mice. Basic Clin. Pharmacol. Toxicol., 2010, 106 (2), P. 114–117.Li J.J.E., Muralikrishnan S., et al. Nanoparticle-induced pulmonary toxicity. Exp. Biol. Med., 2010, 235 (9), P. 1025–1033.Li J.J.E., Muralikrishnan S., et al. Nanoparticle-induced pulmonary toxicity. Exp. Biol. Med., 2010, 235 (9), P. 1025–1033.Cohen J., Deloid G., Pyrgiotakis G., Demokritou P. Interactions of engineered nanomaterials in physiological media and implications for in vitro dosimetry. Nanotoxicology, 2013, 7 (4), P. 417–431.Cohen J., Deloid G., Pyrgiotakis G., Demokritou P. Interactions of engineered nanomaterials in physiological media and implications for in vitro dosimetry. Nanotoxicology, 2013, 7 (4), P. 417–431.Garcia-Orue I., Gainza G., et al. Nanotechnology approaches for skin wound regeneration using drugdelivery systems. Nanobiomaterials in Soft Tissue Engineering, 2016, P. 31–55.Garcia-Orue I., Gainza G., et al. Nanotechnology approaches for skin wound regeneration using drugdelivery systems. Nanobiomaterials in Soft Tissue Engineering, 2016, P. 31–55.Mishra P.K., Mishra H., et al. Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications. Drug Discovery Today, 2017, 22 (12), P. 1825–1834.Mishra P.K., Mishra H., et al. Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications. Drug Discovery Today, 2017, 22 (12), P. 1825–1834.Akila S., Nanda A. In-Vivo Wound Healing Activity of Silver Nanoparticles: An Investigation. Int. J. Sci. Res., 2014, 3 (7), P. 1208–1212.Akila S., Nanda A. In-Vivo Wound Healing Activity of Silver Nanoparticles: An Investigation. Int. J. Sci. Res., 2014, 3 (7), P. 1208–1212.Alizadeh S., Seyedalipour B., et al. Copper nanoparticles promote rapid wound healing in acute full thickness defect via acceleration of skin cell migration, proliferation, and neovascularization. Biochem. Biophys. Res. Commun., 2019, 517 (4), P. 684–690.Alizadeh S., Seyedalipour B., et al. Copper nanoparticles promote rapid wound healing in acute full thickness defect via acceleration of skin cell migration, proliferation, and neovascularization. Biochem. Biophys. Res. Commun., 2019, 517 (4), P. 684–690.Tao B., Lin C., et al. Copper-nanoparticle-embedded hydrogel for killing bacteria and promoting wound healing with photothermal therapy. J. Mater. Chem. B, 2019, 7 (15), P. 2534–2548.Tao B., Lin C., et al. Copper-nanoparticle-embedded hydrogel for killing bacteria and promoting wound healing with photothermal therapy. J. Mater. Chem. B, 2019, 7 (15), P. 2534–2548.Ziv-Polat O., Topaz M., Brosh T., Margel S. Enhancement of incisional wound healing by thrombin conjugated iron oxide nanoparticles. Biomaterials, 2010, 31 (4), P. 741–747.Ziv-Polat O., Topaz M., Brosh T., Margel S. Enhancement of incisional wound healing by thrombin conjugated iron oxide nanoparticles. Biomaterials, 2010, 31 (4), P. 741–747.Hamam F., Nasr A. Curcumin-loaded mesoporous silica particles as wound-healing agent: An in vivo study. Saudi J. Med. Med. Sci., 2020, 8 (1), P. 17–24.Hamam F., Nasr A. Curcumin-loaded mesoporous silica particles as wound-healing agent: An in vivo study. Saudi J. Med. Med. Sci., 2020, 8 (1), P. 17–24.Kheradmand F., Mousavi A., Nurmohamadi E. Zinc and molecular mechanisms involved in its homeostasis. J. Paramed. Faculty, 2009, 4 (1), P. 34–38.Kheradmand F., Mousavi A., Nurmohamadi E. Zinc and molecular mechanisms involved in its homeostasis. J. Paramed. Faculty, 2009, 4 (1), P. 34–38.Jones N., Ray B., Ranjit K.T., Manna A.C. Antibacterial activity of ZnO nanoparticle suspensions on a broad spectrum of microorganisms. FEMS Microbiol. Lett., 2008, 279, P. 71–76.Jones N., Ray B., Ranjit K.T., Manna A.C. Antibacterial activity of ZnO nanoparticle suspensions on a broad spectrum of microorganisms. FEMS Microbiol. Lett., 2008, 279, P. 71–76.Wang S.Q., Tooley I.R. Photoprotection in the era of nanotechnology. Semin. Cutan. Med. Surg., 2011, 30, P. 210–213.Wang S.Q., Tooley I.R. Photoprotection in the era of nanotechnology. Semin. Cutan. Med. Surg., 2011, 30, P. 210–213.Prasad A.S., Oberleas D. Thymidine kinase activity and incorporation of thymidine into DNA in zinc-deficient tissue. J. Lab. Clin. Med., 1974, 83, P. 634–639.Prasad A.S., Oberleas D. Thymidine kinase activity and incorporation of thymidine into DNA in zinc-deficient tissue. J. Lab. Clin. Med., 1974, 83, P. 634–639.Sandstead H.H., Lanier V.C., Shepard G.H., Gillespie D.D. Effects of zinc deficiency and zinc supplementation. Amer. J. Clin. Nutr., 1970, 23, P. 514–519.Sandstead H.H., Lanier V.C., Shepard G.H., Gillespie D.D. Effects of zinc deficiency and zinc supplementation. Amer. J. Clin. Nutr., 1970, 23, P. 514–519.Prasad A.S. Zinc: an overview. Nutr., 1995, 11, P. 93–99.Prasad A.S. Zinc: an overview. Nutr., 1995, 11, P. 93–99.Agren M.S., Chvapil M., Franzen L. Enhancement of re-epithellalization with topical zinc oxide in porcine partialthickness wounds.´ J. Surg. Res., 1991, 50, P. 101–105Agren M.S., Chvapil M., Franzen L. Enhancement of re-epithellalization with topical zinc oxide in porcine partialthickness wounds.´ J. Surg. Res., 1991, 50, P. 101–105Kaushik M., Niranjan R., et al. Investigations on the antimicrobial activity and wound healing potential of ZnO nanoparticles. Appl. Surf. Sci., 2019, 479, P. 1169–1177.Kaushik M., Niranjan R., et al. Investigations on the antimicrobial activity and wound healing potential of ZnO nanoparticles. Appl. Surf. Sci., 2019, 479, P. 1169–1177.Rezende C.P., da Silva J.B., Mohallem N.D.S. Influence of drying on the characteristics of zinc oxide nanoparticles. Braz. J. Phys., 2009, 39, P. 248–251.Rezende C.P., da Silva J.B., Mohallem N.D.S. Influence of drying on the characteristics of zinc oxide nanoparticles. Braz. J. Phys., 2009, 39, P. 248–251.Hajiaghaalipour F., Kanthimathi M.S., Abdulla M.A., Sanusi J. The effect of Camellia sinensis on wound healing potential in an animal model. Evid. Based Compl. Alt. Med., 2013, 386734.Hajiaghaalipour F., Kanthimathi M.S., Abdulla M.A., Sanusi J. The effect of Camellia sinensis on wound healing potential in an animal model. Evid. Based Compl. Alt. Med., 2013, 386734.Abramov Y., Golden B., et al. Histologic characterization of vaginal vs. abdominal surgical wound healing in a rabbit model. Wound Repair Regen., 2007, 15 (1), P. 80–86.Abramov Y., Golden B., et al. Histologic characterization of vaginal vs. abdominal surgical wound healing in a rabbit model. Wound Repair Regen., 2007, 15 (1), P. 80–86.Greenhalgh D.G., Sprugel K.H., Murray M.J., Ross, R. PDGF and FGF stimulate healing in the genetically diabetic mouse. Am. J. Pathol., 1990, 136, P. 1235–1246.Greenhalgh D.G., Sprugel K.H., Murray M.J., Ross, R. PDGF and FGF stimulate healing in the genetically diabetic mouse. Am. J. Pathol., 1990, 136, P. 1235–1246.Kant V., Kumar D., et al. Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats. Cytokine, 2015, 73, P. 144–155.Kant V., Kumar D., et al. Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats. Cytokine, 2015, 73, P. 144–155.Cho K., Wang X., Nie S., Shin D.M. Therapeutic nanoparticles for drug delivery in cancer. Clin, Cancer, Res., 2008, 14, P. 1310–1316.Cho K., Wang X., Nie S., Shin D.M. Therapeutic nanoparticles for drug delivery in cancer. Clin, Cancer, Res., 2008, 14, P. 1310–1316.Fine N., Mustoe T. Wound Healing. Philadelphia: Lippincott Williams & Wilkins, 2006.Fine N., Mustoe T. Wound Healing. Philadelphia: Lippincott Williams & Wilkins, 2006.Wertheimer E. Diabetic skin complications: a need for reorganizing the categories of diabetes-associated complications. Isr. Med. Assoc. J., 2004, 6, P. 287–289.Wertheimer E. Diabetic skin complications: a need for reorganizing the categories of diabetes-associated complications. Isr. Med. Assoc. J., 2004, 6, P. 287–289.Bae S.H., Bae Y.C., Nam S.B., Choi S.J. A Skin Fixation Method For Decreasing The Influence Of Wound Contraction On Wound Healing In A Rat Model. Arch. Plast. Surg., 2012, 39 (5), P. 457–462.Bae S.H., Bae Y.C., Nam S.B., Choi S.J. A Skin Fixation Method For Decreasing The Influence Of Wound Contraction On Wound Healing In A Rat Model. Arch. Plast. Surg., 2012, 39 (5), P. 457–462.Singer A.J., Clark R.A.F. Cutaneous wound healing. N. Engl. J. Med., 1999, 341, P. 738–746.Singer A.J., Clark R.A.F. Cutaneous wound healing. N. Engl. J. Med., 1999, 341, P. 738–746.Werner R., Grose S. Regulation of wound healing by growth factors and cytokines. Physiol. Rev., 2003, 83, P. 835–870.Werner R., Grose S. Regulation of wound healing by growth factors and cytokines. Physiol. Rev., 2003, 83, P. 835–870.Brem H., Folkman J. Angiogenesis and basic fibroblast growth factor during wound healing. In: Friedlander G.E., Lane J.M., (ed.) Bone Formation and Repair, Rosemont: American Academy of Orthopedic Surgeons, 1994, P. 213–222.Brem H., Folkman J. Angiogenesis and basic fibroblast growth factor during wound healing. In: Friedlander G.E., Lane J.M., (ed.) Bone Formation and Repair, Rosemont: American Academy of Orthopedic Surgeons, 1994, P. 213–222.Pereira M.C., Pinho C.B., et al. Influence of 670 nm low-level laser therapy on mast cells and vascular response of cutaneous injuries. J. Photochem. Photobiol. B, 2010, 98, P. 188–192.Pereira M.C., Pinho C.B., et al. Influence of 670 nm low-level laser therapy on mast cells and vascular response of cutaneous injuries. J. Photochem. Photobiol. B, 2010, 98, P. 188–192.Selvam S., Rajiv Gandhi R., et al. Antibacterial effect of novel synthesized sulfated cyclodextrin crosslinkedcotton fabric and its improved antibacterial activities with ZnO, TiO2 and Ag nanoparticles coating. Int. J. Pharm., 2012, 434 (1–2), P. 366–374.Selvam S., Rajiv Gandhi R., et al. Antibacterial effect of novel synthesized sulfated cyclodextrin crosslinkedcotton fabric and its improved antibacterial activities with ZnO, TiO2 and Ag nanoparticles coating. Int. J. Pharm., 2012, 434 (1–2), P. 366–374.Subhasree R.S., Selvakumar D., Kumar N.S. Hydrothermal mediated synthe-sis of ZnO nanorods and their antibacterial properties. Lett. Appl. NanoBioSci., 2012, 1, P. 2–7.Subhasree R.S., Selvakumar D., Kumar N.S. Hydrothermal mediated synthe-sis of ZnO nanorods and their antibacterial properties. Lett. Appl. NanoBioSci., 2012, 1, P. 2–7.Vlad S., Tanase C., et al. Antifungal behaviour of polyurethane membranes with zincoxide nanoparticles. Digest J. Nanomater. Biostruct., 2012, 7, P. 51–58.Vlad S., Tanase C., et al. Antifungal behaviour of polyurethane membranes with zincoxide nanoparticles. Digest J. Nanomater. Biostruct., 2012, 7, P. 51–58.Kumar P.T.S., Lakshmanan V.K., et al. Flexible and microporous chitosanhydrogel/nanoZnO composite bandages for wound dressing: in vitro and in vivoevaluation. ACS Appl. Mater. Interfaces., 2012, 4, P. 2618–2629.Kumar P.T.S., Lakshmanan V.K., et al. Flexible and microporous chitosanhydrogel/nanoZnO composite bandages for wound dressing: in vitro and in vivoevaluation. ACS Appl. Mater. Interfaces., 2012, 4, P. 2618–2629.Shalumon K.T., Anulekha K.H., et al. Sodium alginate/poly vinyl alcohol/nano ZnO composite nanofibers forantibacterial wound dressings. Int. J. Biol. Macromol., 2011, 49, P. 247–254.Shalumon K.T., Anulekha K.H., et al. Sodium alginate/poly vinyl alcohol/nano ZnO composite nanofibers forantibacterial wound dressings. Int. J. Biol. Macromol., 2011, 49, P. 247–254.Hamdan S., Pastar I., et al. Nanotechnology-Driven Therapeutic Interventions in Wound Healing: Potential Uses and Applications. ACS Cent. Sci., 2017, 3, P. 163–175.Hamdan S., Pastar I., et al. Nanotechnology-Driven Therapeutic Interventions in Wound Healing: Potential Uses and Applications. ACS Cent. Sci., 2017, 3, P. 163–175.Lin P.C., Lin S., Wang P.C., Sridhar R. Techniques for physicochemical characterization of nanomaterials. Biotechnol. Adv., 2014, 32, P. 711– 726.Lin P.C., Lin S., Wang P.C., Sridhar R. Techniques for physicochemical characterization of nanomaterials. Biotechnol. Adv., 2014, 32, P. 711– 726.Ferrari M. Nanogeometry: Beyond drug delivery. Nat. Nanotechnol., 2008, 3, P. 131–132.Ferrari M. Nanogeometry: Beyond drug delivery. Nat. Nanotechnol., 2008, 3, P. 131–132.George S., Lin S., et al. Surface defects on plate-shaped silver nanoparticles contribute to its hazard potential in a fish gill cell line and zebrafish embryos. ACS Nano, 2012, 6, P. 3745–3759.George S., Lin S., et al. Surface defects on plate-shaped silver nanoparticles contribute to its hazard potential in a fish gill cell line and zebrafish embryos. ACS Nano, 2012, 6, P. 3745–3759.Liu X., Lee P.Y., et al. Silver nanoparticles mediate differential responses in keratinocytes and fibroblasts during skin wound healing. Chem. Med. Chem., 2010, 5 (3), P. 468–475.Liu X., Lee P.Y., et al. Silver nanoparticles mediate differential responses in keratinocytes and fibroblasts during skin wound healing. Chem. Med. Chem., 2010, 5 (3), P. 468–475.Li X., Wang H., et al. Effect of composite SiO(2) @AuNPs on wound healing: in vitro and vivo studies. J. Colloid. Interface Sci., 2015, 445, P. 312–319.Li X., Wang H., et al. Effect of composite SiO(2) @AuNPs on wound healing: in vitro and vivo studies. J. Colloid. Interface Sci., 2015, 445, P. 312–319.Nadworny P.L., Landry B.K., et al. Does nanocrystalline silver have a transferable effect? Wound Repair Regen., 2010, 18, P. 254–265.Nadworny P.L., Landry B.K., et al. Does nanocrystalline silver have a transferable effect? Wound Repair Regen., 2010, 18, P. 254–265.Archana D., Dutta J., Dutta P.K. Evaluation of chitosan nano dressing for wound healing: characterization, in vitro and in vivo studies. Int. J. Biol. Macromol., 2013, 57, P. 193–203.Archana D., Dutta J., Dutta P.K. Evaluation of chitosan nano dressing for wound healing: characterization, in vitro and in vivo studies. Int. J. Biol. Macromol., 2013, 57, P. 193–203.Chereddy K.K., Coco R., et al. Combined effect of PLGA and curcumin on wound healing activity. J. Control Release, 2013, 171, P. 208–215.Chereddy K.K., Coco R., et al. Combined effect of PLGA and curcumin on wound healing activity. J. Control Release, 2013, 171, P. 208–215.Tiwari M., Narayankan K., et al. Biosynthesis and wound healing activity of copper nanoparticles. IET Nanobiotechnol., 2014, 8, P. 230–237.Tiwari M., Narayankan K., et al. Biosynthesis and wound healing activity of copper nanoparticles. IET Nanobiotechnol., 2014, 8, P. 230–237.Chen S.A., Chen H.M., et al. Topical treatment with antioxidants and Au nanoparticles promote healing of diabetic wound through receptor for advance glycation end-products. Eur. J. Pharm. Sci., 2012, 47, P. 875–883.Chen S.A., Chen H.M., et al. Topical treatment with antioxidants and Au nanoparticles promote healing of diabetic wound through receptor for advance glycation end-products. Eur. J. Pharm. Sci., 2012, 47, P. 875–883.Guthrie K.M., Agarwal A., et al. Integration of silver nanoparticle-impregnated polyelectrolyte multilayers into murine-splinted cutaneous wound beds. J. Burn Care Res., 2013, 34, P. 359–367.Guthrie K.M., Agarwal A., et al. Integration of silver nanoparticle-impregnated polyelectrolyte multilayers into murine-splinted cutaneous wound beds. J. Burn Care Res., 2013, 34, P. 359–367.Kwan K.H., Liu X., et al. Modulation of collagen alignment by silver nanoparticles results in better mechanical properties in wound healing. Nanomed., 2011, 7, P. 497–504.Kwan K.H., Liu X., et al. Modulation of collagen alignment by silver nanoparticles results in better mechanical properties in wound healing. Nanomed., 2011, 7, P. 497–504.Baroni A., Perfetto B., et al. Topical amikacin formulation induces fibroblast growth factorand cytokine releasefrom human dermal fibroblasts. Arch. Dermatol. Res., 1999, 291, P. 296–299.Baroni A., Perfetto B., et al. Topical amikacin formulation induces fibroblast growth factorand cytokine releasefrom human dermal fibroblasts. Arch. Dermatol. Res., 1999, 291, P. 296–299.Tarnow P., Agren M., Steenfos H., Jansson J.O. Topical zinc oxide treatment increases endogenous gene expression of insulin-like growth factor-I (IGF-1) in granulation tissue from porcine wounds. Scand. J. Plast. Reconstr. Surg. Hand. Surg., 1994, 28, P. 255–259.Tarnow P., Agren M., Steenfos H., Jansson J.O. Topical zinc oxide treatment increases endogenous gene expression of insulin-like growth factor-I (IGF-1) in granulation tissue from porcine wounds. Scand. J. Plast. Reconstr. Surg. Hand. Surg., 1994, 28, P. 255–259.Agren M.S. Matrix metalloproteinases (MMPs) are required for re-epithelialization of cutaneous wounds. Arch. Dermatol. Res., 1999, 291, P. 583–590.Agren M.S. Matrix metalloproteinases (MMPs) are required for re-epithelialization of cutaneous wounds. Arch. Dermatol. Res., 1999, 291, P. 583–590.Agren M.S., Steenfos H.H., Tarnow P., Jansson J. Auguments endogenous expression of insulin-like growth factor-I (IGF-I) and activates¨ matrix metalloproteinases (MMPs) in wounds. EWMA J., 2001, 138169909.Agren M.S., Steenfos H.H., Tarnow P., Jansson J. Auguments endogenous expression of insulin-like growth factor-I (IGF-I) and activates¨ matrix metalloproteinases (MMPs) in wounds. EWMA J., 2001, 138169909.Lansdown A.B., Mirastschijski U., et al. Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound Repair Regen., 2007, 15 (1), P. 2–16.Lansdown A.B., Mirastschijski U., et al. Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound Repair Regen., 2007, 15 (1), P. 2–16.Iwata M., Takebayashi T., et al. Zinc accumulation and metallothionein gene expression in the proliferating epidermis during wound healing in mouse skin. Histochem. Cell. Biol., 1999, 112 (4), P. 283–290.Iwata M., Takebayashi T., et al. Zinc accumulation and metallothionein gene expression in the proliferating epidermis during wound healing in mouse skin. Histochem. Cell. Biol., 1999, 112 (4), P. 283–290.

The authors declare that there are no conflicts of interest present.