Skin is the external part of the human body; thus, it is exposed to outer stimuli leading to injuries and damage, due to being the tissue mostly affected by wounds and aging that compromise its protective function. The recent extension of the average lifespan raises the interest in products capable of counteracting skin related health conditions. However, the skin barrier is not easy to permeate and could be influenced by different factors. In the last decades an innovative pharmacotherapeutic approach has been possible thanks to the advent of nanomedicine. Nanodevices can represent an appropriate formulation to enhance the passive penetration, modulate drug solubility and increase the thermodynamic activity of drugs. Here, we summarize the recent nanotechnological approaches to maintain and replace skin homeostasis, with particular attention to nanomaterials applications on wound healing, regeneration and rejuvenation of skin tissue. The different nanomaterials as nanofibers, hydrogels, nanosuspensions, and nanoparticles are described and in particular we highlight their main chemical features that are useful in drug delivery and tissue regeneration.

Center for Developmental Biology and Reprogramming Department of Biomedical Sciences University of Sassari Viale San Pietro 43 B 07100 Sassari Italy

Department of Biomedical Sciences University of Sassari Viale San Pietro 43 B 07100 Sassari Italy

Department of Chemistry and Pharmacy University of Sassari Vienna 2 07100 Sassari Italy

Institute of Biophysics 2nd Faculty of Medicine Charles University 5 Uvalu 84 150 06 Prague 5 Czech Republic

Interuniversity Consortium 1 N B B Viale delle Medaglie d'Oro 305 00136 Roma Italy

UCEEB Czech Technical University Trinecka 1024 27343 Bustehrad Czech Republic

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Lu C., Fuchs E. Sweat gland progenitors in development, homeostasis, and wound repair. Cold Spring Harb. Perspect. Med. 2014;4:a015222. doi: 10.1101/cshperspect.a015222. PubMed DOI PMC

Sen C.K., Gordillo G.M., Roy S., Kirsner R., Lambert L., Hunt T.K., Gottrup F., Gurtner G.C., Longaker M.T. Human skin wounds: A major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17:763–771. doi: 10.1111/j.1524-475X.2009.00543.x. PubMed DOI PMC

Kirkwood T.B., Melov S. On the programmed/non-programmed nature of ageing within the life history. Curr. Biol. 2011;21:R701–R707. doi: 10.1016/j.cub.2011.07.020. PubMed DOI

Brink T.C., Demetrius L., Lehrach H., Adjaye J. Age-related transcriptional changes in gene expression in different organs of mice support the metabolic stability theory of aging. Biogerontology. 2009;10:549–564. doi: 10.1007/s10522-008-9197-8. PubMed DOI PMC

Krutmann J., Morita A., Chung J.H. Sun exposure: What molecular photodermatology tells us about its good and bad sides. J. Investig. Derm. 2012;132:976–984. doi: 10.1038/jid.2011.394. PubMed DOI

Stern M.M., Bickenbach J.R. Epidermal stem cells are resistant to cellular aging. Aging Cell. 2007;6:439–452. doi: 10.1111/j.1474-9726.2007.00318.x. PubMed DOI

Quan T., He T., Kang S., Voorhees J.J., Fisher G.J. Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-beta type II receptor/Smad signaling. Am. J. Pathol. 2004;165:741–751. doi: 10.1016/S0002-9440(10)63337-8. PubMed DOI PMC

Mizukoshi K., Nakamura T., Oba A. The relationship between dermal papillary structure and skin surface properties, color, and elasticity. Ski. Res. Technol. 2016;22:295–304. doi: 10.1111/srt.12260. PubMed DOI

Shin J.W., Kwon S.H., Choi J.Y., Na J.I., Huh C.H., Choi H.R., Park K.C. Molecular Mechanisms of Dermal Aging and Antiaging Approaches. Int. J. Mol. Sci. 2019;20:2126. doi: 10.3390/ijms20092126. PubMed DOI PMC

Kehlet S.N., Willumsen N., Armbrecht G., Dietzel R., Brix S., Henriksen K., Karsdal M.A. Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix. PLoS ONE. 2018;13:e0194458. doi: 10.1371/journal.pone.0194458. PubMed DOI PMC

Varani J., Dame M.K., Rittie L., Fligiel S.E., Kang S., Fisher G.J., Voorhees J.J. Decreased collagen production in chronologically aged skin: Roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am. J. Pathol. 2006;168:1861–1868. doi: 10.2353/ajpath.2006.051302. PubMed DOI PMC

Yurchenco P.D., Schittny J.C. Molecular architecture of basement membranes. FASEB J. 1990;4:1577–1590. doi: 10.1096/fasebj.4.6.2180767. PubMed DOI

Bellu E., Garroni G., Balzano F., Satta R., Montesu M.A., Kralovic M., Fedacko J., Cruciani S., Maioli M. Isolating stem cells from skin: Designing a novel highly efficient non-enzymatic approach. Physiol. Res. 2019;68:S385–S388. doi: 10.33549/physiolres.934373. PubMed DOI

Stadelmann W.K., Digenis A.G., Tobin G.R. Physiology and healing dynamics of chronic cutaneous wounds. Am. J. Surg. 1998;176:26S–38S. doi: 10.1016/S0002-9610(98)00183-4. PubMed DOI

Ahmed A.S., Sheng M.H., Wasnik S., Baylink D.J., Lau K.W. Effect of aging on stem cells. World J. Exp. Med. 2017;7:1–10. doi: 10.5493/wjem.v7.i1.1. PubMed DOI PMC

Rinaldi S., Maioli M., Pigliaru G., Castagna A., Santaniello S., Basoli V., Fontani V., Ventura C. Stem cell senescence. Effects of REAC technology on telomerase-independent and telomerase-dependent pathways. Sci. Rep. 2014;4:6373. doi: 10.1038/srep06373. PubMed DOI PMC

Boukamp P. Non-melanoma skin cancer: What drives tumor development and progression? Carcinogenesis. 2005;26:1657–1667. doi: 10.1093/carcin/bgi123. PubMed DOI

Parrinello S., Coppe J.P., Krtolica A., Campisi J. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation. J. Cell Sci. 2005;118:485–496. doi: 10.1242/jcs.01635. PubMed DOI PMC

Wang Y., Lauer M.E., Anand S., Mack J.A., Maytin E.V. Hyaluronan synthase 2 protects skin fibroblasts against apoptosis induced by environmental stress. J. Biol. Chem. 2014;289:32253–32265. doi: 10.1074/jbc.M114.578377. PubMed DOI PMC

Bellu E., Garroni G., Cruciani S., Balzano F., Serra D., Satta R., Montesu M.A., Fadda A., Mulas M., Sarais G., et al. Smart Nanofibers with Natural Extracts Prevent Senescence Patterning in a Dynamic Cell Culture Model of Human Skin. Cells. 2020;9:2530. doi: 10.3390/cells9122530. PubMed DOI PMC

Kaul S., Gulati N., Verma D., Mukherjee S., Nagaich U. Role of nanotechnology in cosmeceuticals: A review of recent advances. J. Pharm. 2018;2018:3420204. doi: 10.1155/2018/3420204. PubMed DOI PMC

Whitney J.D. Overview: Acute and chronic wounds. Nurs. Clin. N. Am. 2005;40:191–205. doi: 10.1016/j.cnur.2004.09.002. PubMed DOI

Zare M.R., Khorram M., Barzegar S., Asadian F., Zareshahrabadi Z., Jamal Saharkhiz M., Ahadian S., Zomorodian K. Antimicrobial core-shell electrospun nanofibers containing Ajwain essential oil for accelerating infected wound healing. Int. J. Pharm. 2021;603:120698. doi: 10.1016/j.ijpharm.2021.120698. PubMed DOI

Braund R., Hook S., Medlicott N.J. The role of topical growth factors in chronic wounds. Curr. Drug Deliv. 2007;4:195–204. doi: 10.2174/156720107781023857. PubMed DOI

Gainza G., Villullas S., Pedraz J.L., Hernandez R.M., Igartua M. Advances in drug delivery systems (DDSs) to release growth factors for wound healing and skin regeneration. Nanomedicine. 2015;11:1551–1573. doi: 10.1016/j.nano.2015.03.002. PubMed DOI

Addis R., Cruciani S., Santaniello S., Bellu E., Sarais G., Ventura C., Maioli M., Pintore G. Fibroblast Proliferation and Migration in Wound Healing by Phytochemicals: Evidence for a Novel Synergic Outcome. Int. J. Med. Sci. 2020;17:1030–1042. doi: 10.7150/ijms.43986. PubMed DOI PMC

Oda Y., Bikle D.D. Vitamin D and calcium signaling in epidermal stem cells and their regeneration. World J. Stem Cells. 2020;12:604–611. doi: 10.4252/wjsc.v12.i7.604. PubMed DOI PMC

Kim E.K., Kim H.O., Park Y.M., Park C.J., Yu D.S., Lee J.Y. Prevalence and risk factors of depression in geriatric patients with dermatological diseases. Ann. Derm. 2013;25:278–284. doi: 10.5021/ad.2013.25.3.278. PubMed DOI PMC

Bolzinger M.-A., Briançon S., Pelletier J., Chevalier Y. Penetration of drugs through skin, a complex rate-controlling membrane. Curr. Opin. Colloid Interface Sci. 2012;17:156–165. doi: 10.1016/j.cocis.2012.02.001. DOI

Trommer H., Neubert R.H. Overcoming the stratum corneum: The modulation of skin penetration. A review. Ski. Pharm. Physiol. 2006;19:106–121. doi: 10.1159/000091978. PubMed DOI

Batisse D., Bazin R., Baldeweck T., Querleux B., Leveque J.L. Influence of age on the wrinkling capacities of skin. Ski. Res. Technol. 2002;8:148–154. doi: 10.1034/j.1600-0846.2002.10308.x. PubMed DOI

Rennick J.J., Johnston A.P.R., Parton R.G. Key principles and methods for studying the endocytosis of biological and nanoparticle therapeutics. Nat. Nanotechnol. 2021;16:266–276. doi: 10.1038/s41565-021-00858-8. PubMed DOI

Vitorino C., Almeida J., Goncalves L.M., Almeida A.J., Sousa J.J., Pais A.A. Co-encapsulating nanostructured lipid carriers for transdermal application: From experimental design to the molecular detail. J. Control. Release. 2013;167:301–314. doi: 10.1016/j.jconrel.2013.02.011. PubMed DOI

Naik A., Kalia Y.N., Guy R.H. Transdermal drug delivery: Overcoming the skin’s barrier function. Pharm. Sci. Technol. Today. 2000;3:318–326. doi: 10.1016/S1461-5347(00)00295-9. PubMed DOI

Kurian S.J., Miraj S.S., Benson R., Munisamy M., Saravu K., Rodrigues G.S., Rao M. Vitamin D Supplementation in Diabetic Foot Ulcers: A Current Perspective. Curr. Diabetes Rev. 2021;17:512–521. doi: 10.2174/1573399816999201012195735. PubMed DOI

Cruciani S., Santaniello S., Garroni G., Fadda A., Balzano F., Bellu E., Sarais G., Fais G., Mulas M., Maioli M. Myrtus Polyphenols, from Antioxidants to Anti-Inflammatory Molecules: Exploring a Network Involving Cytochromes P450 and Vitamin D. Molecules. 2019;24:1515. doi: 10.3390/molecules24081515. PubMed DOI PMC

Barry B.W. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur. J. Pharm. Sci. 2001;14:101–114. doi: 10.1016/S0928-0987(01)00167-1. PubMed DOI

Benson H.A. Transdermal drug delivery: Penetration enhancement techniques. Curr. Drug Deliv. 2005;2:23–33. doi: 10.2174/1567201052772915. PubMed DOI

Landsiedel R., Ma-Hock L., Van Ravenzwaay B., Schulz M., Wiench K., Champ S., Schulte S., Wohlleben W., Oesch F. Gene toxicity studies on titanium dioxide and zinc oxide nanomaterials used for UV-protection in cosmetic formulations. Nanotoxicology. 2010;4:364–381. doi: 10.3109/17435390.2010.506694. PubMed DOI

Nardini M., Perteghella S., Mastracci L., Grillo F., Marrubini G., Bari E., Formica M., Gentili C., Cancedda R., Torre M.L., et al. Growth Factors Delivery System for Skin Regeneration: An Advanced Wound Dressing. Pharmaceutics. 2020;12:120. doi: 10.3390/pharmaceutics12020120. PubMed DOI PMC

Fathi-Azarbayjani A., Qun L., Chan Y.W., Chan S.Y. Novel vitamin and gold-loaded nanofiber facial mask for topical delivery. AAPS PharmSciTech. 2010;11:1164–1170. doi: 10.1208/s12249-010-9475-z. PubMed DOI PMC

Jeevanandam J., Barhoum A., Chan Y.S., Dufresne A., Danquah M.K. Review on nanoparticles and nanostructured materials: History, sources, toxicity and regulations. Beilstein J. Nanotechnol. 2018;9:1050–1074. doi: 10.3762/bjnano.9.98. PubMed DOI PMC

Gustafson H.H., Holt-Casper D., Grainger D.W., Ghandehari H. Nanoparticle uptake: The phagocyte problem. Nano Today. 2015;10:487–510. doi: 10.1016/j.nantod.2015.06.006. PubMed DOI PMC

Chou L.Y., Ming K., Chan W.C. Strategies for the intracellular delivery of nanoparticles. Chem. Soc. Rev. 2011;40:233–245. doi: 10.1039/C0CS00003E. PubMed DOI

Li K., Li D., Li C.-H., Zhuang P., Dai C., Hu X., Wang D., Liu Y., Mei X., Rotello V.M. Efficient in vivo wound healing using noble metal nanoclusters. Nanoscale. 2021;13:6531–6537. doi: 10.1039/D0NR07176E. PubMed DOI PMC

Lo S., Fauzi M.B. Current Update of Collagen Nanomaterials—Fabrication, Characterisation and Its Applications: A Review. Pharmaceutics. 2021;13:316. doi: 10.3390/pharmaceutics13030316. PubMed DOI PMC

Ovais M., Ahmad I., Khalil A.T., Mukherjee S., Javed R., Ayaz M., Raza A., Shinwari Z.K. Wound healing applications of biogenic colloidal silver and gold nanoparticles: Recent trends and future prospects. Appl. Microbiol. Biotechnol. 2018;102:4305–4318. doi: 10.1007/s00253-018-8939-z. PubMed DOI

Neema S., Chatterjee M. Nano-silver dressing in toxic epidermal necrolysis. Indian J. Dermatol. Venereol. Leprol. 2017;83 doi: 10.4103/0378-6323.192955. PubMed DOI

Ribeiro F.M., de Oliveira M.M., Singh S., Sakthivel T.S., Neal C.J., Seal S., Ueda-Nakamura T., Lautenschlager S.d.O.S., Nakamura C.V. Ceria Nanoparticles decrease UVA-induced fibroblast death through cell redox regulation leading to cell survival, migration and proliferation. Front. Bioeng. Biotechnol. 2020;8:577557. doi: 10.3389/fbioe.2020.577557. PubMed DOI PMC

Alizadeh S., Seyedalipour B., Shafieyan S., Kheime A., Mohammadi P., Aghdami N. 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;517:684–690. doi: 10.1016/j.bbrc.2019.07.110. PubMed DOI

Medici S., Peana M., Nurchi V.M., Zoroddu M.A. Medical uses of silver: History, myths, and scientific evidence. J. Med. Chem. 2019;62:5923–5943. doi: 10.1021/acs.jmedchem.8b01439. PubMed DOI

Akram M., Hussain R. Nanocellulose and Nanohydrogel Matrices: Biotechnological and Biomedical Applications. Wiley Online Library; Hoboken, NJ, USA: 2017. Nanohydrogels: History, development, and applications in drug delivery; pp. 297–330.

Paiva-Santos A.C., Herdade A.M., Guerra C., Peixoto D., Pereira-Silva M., Zeinali M., Mascarenhas-Melo F., Paranhos A., Veiga F. Plant-mediated green synthesis of metal-based nanoparticles for dermopharmaceutical and cosmetic applications. Int. J. Pharm. 2021;597:120311. doi: 10.1016/j.ijpharm.2021.120311. PubMed DOI

Kong Y., Hou Z., Zhou L., Zhang P., Ouyang Y., Wang P., Chen Y., Luo X. Injectable Self-Healing Hydrogels Containing CuS Nanoparticles with Abilities of Hemostasis, Antibacterial activity, and Promoting Wound Healing. ACS Biomater. Sci. Eng. 2021;7:335–349. doi: 10.1021/acsbiomaterials.0c01473. PubMed DOI

Manatunga D., Godakanda V., Herath H., de Silva R.M., Yeh C.-Y., Chen J.-Y., Akshitha de Silva A., Rajapaksha S., Nilmini R., Nalin de Silva K. Nanofibrous cosmetic face mask for transdermal delivery of nano gold: Synthesis, characterization, release and zebra fish employed toxicity studies. R. Soc. Open Sci. 2020;7:201266. doi: 10.1098/rsos.201266. PubMed DOI PMC

Jiménez-Pérez Z.E., Singh P., Kim Y.-J., Mathiyalagan R., Kim D.-H., Lee M.H., Yang D.C. Applications of Panax ginseng leaves-mediated gold nanoparticles in cosmetics relation to antioxidant, moisture retention, and whitening effect on B16BL6 cells. J. Ginseng Res. 2018;42:327–333. doi: 10.1016/j.jgr.2017.04.003. PubMed DOI PMC

Taufikurohmah T., Sanjaya I.G.M., Syahrani A. Nanogold synthesis using matrix mono glyceryl stearate as antiaging compounds in modern cosmetics. J. Mater. Sci. Eng. A. 2011;1:857.

Arafa M.G., El-Kased R.F., Elmazar M. Thermoresponsive gels containing gold nanoparticles as smart antibacterial and wound healing agents. Sci. Rep. 2018;8:13674. doi: 10.1038/s41598-018-31895-4. PubMed DOI PMC

Stefan L.M., Iosageanu A., Ilie D., Stanciuc A.M., Matei C., Berger D., Craciunescu O. Extracellular matrix biomimetic polymeric membranes enriched with silver nanoparticles for wound healing. Biomed. Mater. 2021;16:035010. doi: 10.1088/1748-605X/abe55d. PubMed DOI

Bundjaja V., Santoso S.P., Angkawijaya A.E., Yuliana M., Soetaredjo F.E., Ismadji S., Ayucitra A., Gunarto C., Ju Y.-H., Ho M.-H. Fabrication of cellulose carbamate hydrogel-dressing with rarasaponin surfactant for enhancing adsorption of silver nanoparticles and antibacterial activity. Mater. Sci. Eng. C. 2021;118:111542. doi: 10.1016/j.msec.2020.111542. PubMed DOI

Amer S., Attia N., Nouh S., El-Kammar M., Korittum A., Abu-Ahmed H. Fabrication of sliver nanoparticles/polyvinyl alcohol/gelatin ternary nanofiber mats for wound healing application. J. Biomater. Appl. 2020;35:287–298. doi: 10.1177/0885328220927317. PubMed DOI

Rahman M.A., Islam M.S., Haque P., Khan M.N., Takafuji M., Begum M., Chowdhury G.W., Khan M., Rahman M.M. Calcium ion mediated rapid wound healing by nano-ZnO doped calcium phosphate-chitosan-alginate biocomposites. Materialia. 2020;13:100839. doi: 10.1016/j.mtla.2020.100839. DOI

Zhou L., Chen F., Hou Z., Chen Y., Luo X. Injectable self-healing CuS nanoparticle complex hydrogels with antibacterial, anti-cancer, and wound healing properties. Chem. Eng. J. 2021;409:128224. doi: 10.1016/j.cej.2020.128224. DOI

Ahmed K.B.A., Anbazhagan V. Synthesis of copper sulfide nanoparticles and evaluation of in vitro antibacterial activity and in vivo therapeutic effect in bacteria-infected zebrafish. RSC Adv. 2017;7:36644–36652. doi: 10.1039/C7RA05636B. DOI

Haghniaz R., Rabbani A., Vajhadin F., Khan T., Kousar R., Khan A.R., Montazerian H., Iqbal J., Libanori A., Kim H.J., et al. Anti-bacterial and wound healing-promoting effects of zinc ferrite nanoparticles. J. Nanobiotechnol. 2021;19:38. doi: 10.1186/s12951-021-00776-w. PubMed DOI PMC

Patel K.K., Surekha D.B., Tripathi M., Anjum M.M., Muthu M., Tilak R., Agrawal A.K., Singh S. Antibiofilm potential of silver sulfadiazine-loaded nanoparticle formulations: A study on the effect of DNase-I on microbial biofilm and wound healing activity. Mol. Pharm. 2019;16:3916–3925. doi: 10.1021/acs.molpharmaceut.9b00527. PubMed DOI

Singh S.K., Dhyani A., Juyal D. Hydrogel: Preparation, characterization and applications. Pharma Innov. 2017;6:25.

Asadi N., Pazoki-Toroudi H., Del Bakhshayesh A.R., Akbarzadeh A., Davaran S., Annabi N. Multifunctional hydrogels for wound healing: Special focus on biomacromolecular based hydrogels. Int. J. Biol. Macromol. 2021;170:728–750. doi: 10.1016/j.ijbiomac.2020.12.202. PubMed DOI

Jiang Y., Krishnan N., Heo J., Fang R.H., Zhang L. Nanoparticle–hydrogel superstructures for biomedical applications. J. Control. Release. 2020;324:505–521. doi: 10.1016/j.jconrel.2020.05.041. PubMed DOI PMC

Hoffman A.S. Hydrogels for biomedical applications. Adv. Drug Deliv. Rev. 2012;64:18–23. doi: 10.1016/j.addr.2012.09.010. PubMed DOI

Qiu L., Wang C., Lan M., Guo Q., Du X., Zhou S., Cui P., Hong T., Jiang P., Wang J. Antibacterial Photodynamic Gold Nanoparticles for Skin Infection. ACS Appl. Bio Mater. 2021;4:3124–3132. doi: 10.1021/acsabm.0c01505. PubMed DOI

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;279:71–76. doi: 10.1111/j.1574-6968.2007.01012.x. PubMed DOI

Li S., Dong S., Xu W., Tu S., Yan L., Zhao C., Ding J., Chen X. Antibacterial Hydrogels. Adv. Sci. 2018;5:1700527. doi: 10.1002/advs.201700527. PubMed DOI PMC

Zhao X., Li P., Guo B., Ma P.X. Antibacterial and conductive injectable hydrogels based on quaternized chitosan-graft-polyaniline/oxidized dextran for tissue engineering. Acta Biomater. 2015;26:236–248. doi: 10.1016/j.actbio.2015.08.006. PubMed DOI

Atefyekta S., Blomstrand E., Rajasekharan A.K., Svensson S., Trobos M., Hong J., Webster T.J., Thomsen P., Andersson M. Antimicrobial Peptide-Functionalized Mesoporous Hydrogels. ACS Biomater. Sci. Eng. 2021;7:1693–1702. doi: 10.1021/acsbiomaterials.1c00029. PubMed DOI PMC

Azoulay Z., Aibinder P., Gancz A., Moran-Gilad J., Navon-Venezia S., Rapaport H. Assembly of cationic and amphiphilic beta-sheet FKF tripeptide confers antibacterial activity. Acta Biomater. 2021;125:231–241. doi: 10.1016/j.actbio.2021.02.015. PubMed DOI

Xu M., Li Q., Fang Z., Jin M., Zeng Q., Huang G., Jia Y.G., Wang L., Chen Y. Conductive and antimicrobial macroporous nanocomposite hydrogels generated from air-in-water Pickering emulsions for neural stem cell differentiation and skin wound healing. Biomater. Sci. 2020;8:6957–6968. doi: 10.1039/D0BM01466D. PubMed DOI

Lei J., Sun L., Huang S., Zhu C., Li P., He J., Mackey V., Coy D.H., He Q. The antimicrobial peptides and their potential clinical applications. Am. J. Transl. Res. 2019;11:3919. PubMed PMC

Sadidi H., Hooshmand S., Ahmadabadi A., Javad Hosseini S., Baino F., Vatanpour M., Kargozar S. Cerium Oxide Nanoparticles (Nanoceria): Hopes in Soft Tissue Engineering. Molecules. 2020;25:4559. doi: 10.3390/molecules25194559. PubMed DOI PMC

Yu R., Yang Y., He J., Li M., Guo B. Novel supramolecular self-healing silk fibroin-based hydrogel via host–guest interaction as wound dressing to enhance wound healing. Chem. Eng. J. 2021;417:128278. doi: 10.1016/j.cej.2020.128278. DOI

Contardi M., Kossyvaki D., Picone P., Summa M., Guo X., Heredia-Guerrero J.A., Giacomazza D., Carzino R., Goldoni L., Scoponi G. Electrospun Polyvinylpyrrolidone (PVP) hydrogels containing hydroxycinnamic acid derivatives as potential wound dressings. Chem. Eng. J. 2021;409:128144. doi: 10.1016/j.cej.2020.128144. DOI

Ahmadian Z., Correia A., Hasany M., Figueiredo P., Dobakhti F., Eskandari M.R., Hosseini S.H., Abiri R., Khorshid S., Hirvonen J., et al. A Hydrogen-Bonded Extracellular Matrix-Mimicking Bactericidal Hydrogel with Radical Scavenging and Hemostatic Function for pH-Responsive Wound Healing Acceleration. Adv. Healthc. Mater. 2021;10:e2001122. doi: 10.1002/adhm.202001122. PubMed DOI

Silva V.C., Silva A.M., Basílio J.A., Xavier J.A., do Nascimento T.G., Naal R.M., Del Lama M.P., Leonelo L.A., Mergulhão N.L., Maranhão F.C. New Insights for Red Propolis of Alagoas—Chemical Constituents, Topical Membrane Formulations and Their Physicochemical and Biological Properties. Molecules. 2020;25:5811. doi: 10.3390/molecules25245811. PubMed DOI PMC

Ditta L.A., Rao E., Provenzano F., Sanchez J.L., Santonocito R., Passantino R., Costa M.A., Sabatino M.A., Dispenza C., Giacomazza D., et al. Agarose/kappa-carrageenan-based hydrogel film enriched with natural plant extracts for the treatment of cutaneous wounds. Int. J. Biol. Macromol. 2020;164:2818–2830. doi: 10.1016/j.ijbiomac.2020.08.170. PubMed DOI

Back P.I., Balestrin L.A., Fachel F.N.S., Nemitz M.C., Falkembach M., Soares G., Marques M.D.S., Silveira T., Dal Pra M., Horn A.P., et al. Hydrogels containing soybean isoflavone aglycones-rich fraction-loaded nanoemulsions for wound healing treatment—In vitro and in vivo studies. Colloids Surf. B Biointerfaces. 2020;196:111301. doi: 10.1016/j.colsurfb.2020.111301. PubMed DOI

Sami D.G., Abdellatif A., Azzazy H.M.E. Turmeric/oregano formulations for treatment of diabetic ulcer wounds. Drug Dev. Ind. Pharm. 2020;46:1613–1621. doi: 10.1080/03639045.2020.1811305. PubMed DOI

Zhang W., Qi X., Zhao Y., Liu Y., Xu L., Song X., Xiao C., Yuan X., Zhang J., Hou M. Study of injectable Blueberry anthocyanins-loaded hydrogel for promoting full-thickness wound healing. Int. J. Pharm. 2020;586:119543. doi: 10.1016/j.ijpharm.2020.119543. PubMed DOI

Zhu Y., Hoshi R., Chen S., Yi J., Duan C., Galiano R.D., Zhang H.F., Ameer G.A. Sustained release of stromal cell derived factor-1 from an antioxidant thermoresponsive hydrogel enhances dermal wound healing in diabetes. J. Control. Release. 2016;238:114–122. doi: 10.1016/j.jconrel.2016.07.043. PubMed DOI

Sánchez-Abella L., Ruiz V., Pérez-San Vicente A., Grande H.-J., Loinaz I., Dupin D. Reactive oxygen species (ROS)-responsive biocompatible polyethylene glycol nanocomposite hydrogels with different graphene derivatives. J. Mater. Sci. 2021;56:10041–10052. doi: 10.1007/s10853-021-05919-w. DOI

Gallelli G., Cione E., Serra R., Leo A., Citraro R., Matricardi P., Di Meo C., Bisceglia F., Caroleo M.C., Basile S. Nano-hydrogel embedded with quercetin and oleic acid as a new formulation in the treatment of diabetic foot ulcer: A pilot study. Int. Wound J. 2020;17:485–490. doi: 10.1111/iwj.13299. PubMed DOI PMC

Zhang J., Zheng Y., Lee J., Hua J., Li S., Panchamukhi A., Yue J., Gou X., Xia Z., Zhu L., et al. A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing. Nat. Commun. 2021;12:1670. doi: 10.1038/s41467-021-21964-0. PubMed DOI PMC

Gugerell A., Gouya-Lechner G., Hofbauer H., Laggner M., Trautinger F., Almer G., Peterbauer-Scherb A., Seibold M., Hoetzenecker W., Dreschl C., et al. Safety and clinical efficacy of the secretome of stressed peripheral blood mononuclear cells in patients with diabetic foot ulcer-study protocol of the randomized, placebo-controlled, double-blind, multicenter, international phase II clinical trial MARSYAS II. Trials. 2021;22:10. doi: 10.1186/s13063-020-04948-1. PubMed DOI PMC

Hu C., Long L., Cao J., Zhang S., Wang Y. Dual-crosslinked mussel-inspired smart hydrogels with enhanced antibacterial and angiogenic properties for chronic infected diabetic wound treatment via pH-responsive quick cargo release. Chem. Eng. J. 2021;411:128564. doi: 10.1016/j.cej.2021.128564. DOI

Li H., Yin D., Li W., Tang Q., Zou L., Peng Q. Polydopamine-based nanomaterials and their potentials in advanced drug delivery and therapy. Colloids Surf. B. 2020;199:111502. doi: 10.1016/j.colsurfb.2020.111502. PubMed DOI

Cao M., Li J., Tang J., Chen C., Zhao Y. Gold Nanomaterials in Consumer Cosmetics Nanoproducts: Analyses, Characterization, and Dermal Safety Assessment. Small. 2016;12:5488–5496. doi: 10.1002/smll.201601574. PubMed DOI

Ben Haddada M., Gerometta E., Chawech R., Sorres J., Bialecki A., Pesnel S., Spadavecchia J., Morel A.-L. Assessment of antioxidant and dermoprotective activities of gold nanoparticles as safe cosmetic ingredient. Colloids Surf. B. 2020;189:110855. doi: 10.1016/j.colsurfb.2020.110855. PubMed DOI

Wang Y., Li M., Rong J., Nie G., Qiao J., Wang H., Wu D., Su Z., Niu Z., Huang Y. Enhanced orientation of PEO polymer chains induced by nanoclays in electrospun PEO/clay composite nanofibers. Colloid. Polym. Sci. 2013;291:1541–1546. doi: 10.1007/s00396-012-2875-8. DOI

Righi T.M., Almeida R.S., d’Ávila M.A. Electrospinning of Gelatin/PEO Blends: Influence of Process Parameters in the Nanofiber Properties. Macromol. Symp. 2012;319:230–234. doi: 10.1002/masy.201100137. DOI

Panzavolta S., Gioffrè M., Focarete M.L., Gualandi C., Foroni L., Bigi A. Electrospun gelatin nanofibers: Optimization of genipin cross-linking to preserve fiber morphology after exposure to water. Acta Biomater. 2011;7:1702–1709. doi: 10.1016/j.actbio.2010.11.021. PubMed DOI

Farokhzad O.C., Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3:16–20. doi: 10.1021/nn900002m. PubMed DOI

Sylvester M.A., Amini F., Tan C.K. Electrospun nanofibers in wound healing. Mater. Today Proc. 2020;29:1–6. doi: 10.1016/j.matpr.2020.05.686. DOI

Sahana T., Rekha P. Biopolymers: Applications in wound healing and skin tissue engineering. Mol. Biol. Rep. 2018;45:2857–2867. doi: 10.1007/s11033-018-4296-3. PubMed DOI

Mir M., Ali M.N., Barakullah A., Gulzar A., Arshad M., Fatima S., Asad M. Synthetic polymeric biomaterials for wound healing: A review. Prog. Biomater. 2018;7:1–21. doi: 10.1007/s40204-018-0083-4. PubMed DOI PMC

Andreu V., Mendoza G., Arruebo M., Irusta S. Smart dressings based on nanostructured fibers containing natural origin antimicrobial, anti-inflammatory, and regenerative compounds. Materials. 2015;8:5154–5193. doi: 10.3390/ma8085154. PubMed DOI PMC

Gao C., Zhang L., Wang J., Jin M., Tang Q., Chen Z., Cheng Y., Yang R., Zhao G. Electrospun nanofibers promote wound healing: Theories, techniques, and perspectives. J. Mater. Chem. B. 2021;9:3106–3130. doi: 10.1039/D1TB00067E. PubMed DOI

Lanno G.-M., Ramos C., Preem L., Putrinš M., Laidmäe I., Tenson T., Kogermann K. Antibacterial Porous Electrospun Fibers as Skin Scaffolds for Wound Healing Applications. ACS Omega. 2020;5:30011–30022. doi: 10.1021/acsomega.0c04402. PubMed DOI PMC

Coelho D.S., Veleirinho B., Alberti T., Maestri A., Yunes R., Dias P.F., Maraschin M. Nanomaterials: Toxicity, Human Health and Environment. BoD—Books on Demand; Norderstedt, Germany: 2018. Electrospinning technology: Designing nanofibers toward wound healing application; pp. 1–19.

Beznoska J., Uhlik J., Kestlerova A., Kralovic M., Divin R., Fedacko J., Benes J., Benes M., Vocetkova K., Sovkova V., et al. PVA and PCL nanofibers are suitable for tissue covering and regeneration. Physiol. Res. 2019;68:S501–S508. doi: 10.33549/physiolres.934389. PubMed DOI

Vocetkova K., Sovkova V., Buzgo M., Lukasova V., Divin R., Rampichova M., Blazek P., Zikmund T., Kaiser J., Karpisek Z., et al. A Simple Drug Delivery System for Platelet-Derived Bioactive Molecules, to Improve Melanocyte Stimulation in Vitiligo Treatment. Nanomaterials. 2020;10:1801. doi: 10.3390/nano10091801. PubMed DOI PMC

Vocetkova K., Buzgo M., Sovkova V., Bezdekova D., Kneppo P., Amler E. Nanofibrous polycaprolactone scaffolds with adhered platelets stimulate proliferation of skin cells. Cell Prolif. 2016;49:568–578. doi: 10.1111/cpr.12276. PubMed DOI PMC

Liu Y., Zhou S., Gao Y., Zhai Y. Electrospun nanofibers as a wound dressing for treating diabetic foot ulcer. Asian J. Pharm. Sci. 2019;14:130–143. doi: 10.1016/j.ajps.2018.04.004. PubMed DOI PMC

Hivechi A., Milan P.B., Modabberi K., Amoupour M., Ebrahimzadeh K., Gholipour A.R., Sedighi F., Amini N., Bahrami S.H., Rezapour A., et al. Synthesis and Characterization of Exopolysaccharide Encapsulated PCL/Gelatin Skin Substitute for Full-Thickness Wound Regeneration. Polymers. 2021;13:854. doi: 10.3390/polym13060854. PubMed DOI PMC

Zhu C., Cao R., Zhang Y., Chen R. Metallic Ions Encapsulated in Electrospun Nanofiber for Antibacterial and Angiogenesis Function to Promote Wound Repair. Front. Cell Dev. Biol. 2021;9:660571. doi: 10.3389/fcell.2021.660571. PubMed DOI PMC

Ahmed M., Zayed M., El-Dek S., Hady M.A., El Sherbiny D.H., Uskoković V. Nanofibrous ε-polycaprolactone scaffolds containing Ag-doped magnetite nanoparticles: Physicochemical characterization and biological testing for wound dressing applications in vitro and in vivo. Bioact. Mater. 2021;6:2070–2088. doi: 10.1016/j.bioactmat.2020.12.026. PubMed DOI PMC

Mirmajidi T., Chogan F., Rezayan A.H., Sharifi A.M. In vitro and in vivo evaluation of a nanofiber wound dressing loaded with melatonin. Int. J. Pharm. 2021;596:120213. doi: 10.1016/j.ijpharm.2021.120213. PubMed DOI

Dankova J., Buzgo M., Vejpravova J., Kubickova S., Sovkova V., Vyslouzilova L., Mantlikova A., Necas A., Amler E. Highly efficient mesenchymal stem cell proliferation on poly-epsilon-caprolactone nanofibers with embedded magnetic nanoparticles. Int. J. Nanomed. 2015;10:7307–7317. doi: 10.2147/IJN.S93670. PubMed DOI PMC

Graça M.F.P., de Melo-Diogo D., Correia I.J., Moreira A.F. Electrospun Asymmetric Membranes as Promising Wound Dressings: A Review. Pharmaceutics. 2021;13:183. doi: 10.3390/pharmaceutics13020183. PubMed DOI PMC

Joshi A., Xu Z., Ikegami Y., Yoshida K., Sakai Y., Joshi A., Kaur T., Nakao Y., Yamashita Y.-I., Baba H. Exploiting synergistic effect of externally loaded bFGF and endogenous growth factors for accelerated wound healing using heparin functionalized PCL/gelatin co-spun nanofibrous patches. Chem. Eng. J. 2021;404:126518. doi: 10.1016/j.cej.2020.126518. DOI

Sharma P., Kumar A., Dey A.D., Behl T., Chadha S. Stem cells and growth factors-based delivery approaches for chronic wound repair and regeneration: A promise to heal from within. Life Sci. 2021;268:118932. doi: 10.1016/j.lfs.2020.118932. PubMed DOI

Başaran D.D.A., Gündüz U., Tezcaner A., Keskin D. Topical delivery of heparin from PLGA nanoparticles entrapped in nanofibers of sericin/gelatin scaffolds for wound healing. Int. J. Pharm. 2021;597:120207. doi: 10.1016/j.ijpharm.2021.120207. PubMed DOI

Marshall C.D., Hu M.S., Leavitt T., Barnes L.A., Lorenz H.P., Longaker M.T. Cutaneous scarring: Basic science, current treatments, and future directions. Adv. Wound Care. 2018;7:29–45. doi: 10.1089/wound.2016.0696. PubMed DOI PMC

Mulholland E.J. Electrospun biomaterials in the treatment and prevention of scars in skin wound healing. Front. Bioeng. Biotechnol. 2020;8:481. doi: 10.3389/fbioe.2020.00481. PubMed DOI PMC

Basar A., Castro S., Torres-Giner S., Lagaron J., Sasmazel H.T. Novel poly (ε-caprolactone)/gelatin wound dressings prepared by emulsion electrospinning with controlled release capacity of Ketoprofen anti-inflammatory drug. Mater. Sci. Eng. C. 2017;81:459–468. doi: 10.1016/j.msec.2017.08.025. PubMed DOI

Atiyeh B.S., Amm C.A., El Musa K.A. Improved scar quality following primary and secondary healing of cutaneous wounds. Aesthetic Plast. Surg. 2003;27:411–417. doi: 10.1007/s00266-003-3049-3. PubMed DOI

Woo H., Joo O., Min J., Mi B., Jung H., Ri Y., Chae M., Hyeon S., Ren J., Seok C. Wound healing effect of electrospun silk fibroin nanomatrix in burn-model. Int. J. Biol. Macromol. 2016;85:29–39. PubMed

Hadjizadeh A., Ghasemkhah F., Ghasemzaie N. Polymeric scaffold based gene delivery strategies to improve angiogenesis in tissue engineering: A review. Polym. Rev. 2017;57:505–556. doi: 10.1080/15583724.2017.1292402. DOI

Venkataraman M., Nagarsenker M. Silver sulfadiazine nanosystems for burn therapy. AAPS PharmSciTech. 2013;14:254–264. doi: 10.1208/s12249-012-9914-0. PubMed DOI PMC

Kurowska A., Ghate V., Kodoth A., Shah A., Shah A., Vishalakshi B., Prakash B., Lewis S.A. Non-Propellant Foams of Green Nano-Silver and Sulfadiazine: Development and In Vivo Evaluation for Burn Wounds. Pharm. Res. 2019;36:1–18. doi: 10.1007/s11095-019-2658-8. PubMed DOI

Alipour R., Khorshidi A., Shojaei A.F., Mashayekhi F., Moghaddam M.J.M. Silver Sulfadiazine-loaded PVA/CMC Nanofibers for the Treatment of Wounds Caused by Excision. Fibers Polym. 2019;20:2461–2469. doi: 10.1007/s12221-019-9314-0. DOI

Ahmed M.E., Khalaf Z.Z., Ghafil J.A., Al-Awadi A.Q. Effects of Silver Nanoparticles on Biofilms of Streptococcus Spps. Exec. Ed. 2018;9:1216. doi: 10.5958/0976-5506.2018.02016.8. DOI

Pérez-Díaz M.A., Silva-Bermudez P., Jiménez-López B., Martínez-López V., Melgarejo-Ramírez Y., Brena-Molina A., Ibarra C., Baeza I., Martínez-Pardo M.E., Reyes-Frías M.L. Silver-pig skin nanocomposites and mesenchymal stem cells: Suitable antibiofilm cellular dressings for wound healing. J. Nanobiotechnol. 2018;16:1–16. doi: 10.1186/s12951-017-0331-0. PubMed DOI PMC

El-Deeb N.M., Abo-Eleneen M.A., Al-Madboly L.A., Sharaf M.M., Othman S.S., Ibrahim O.M., Mubarak M.S. Biogenically Synthesized Polysaccharides-Capped Silver Nanoparticles: Immunomodulatory and Antibacterial Potentialities Against Resistant Pseudomonas aeruginosa. Front. Bioeng. Biotechnol. 2020;8:643. doi: 10.3389/fbioe.2020.00643. PubMed DOI PMC

Ahumada M., Lazurko C., Khatoon Z., Goel K., Sedlakova V., Cimenci C.E., Zhang L., Mah T.-F., Franco W., Suuronen E.J. Multifunctional Nano and Collagen-Based Therapeutic Materials for Skin Repair. ACS Biomater. Sci. Eng. 2020;6:1124–1134. PubMed

Krutmann J., Schalka S., Watson R.E.B., Wei L., Morita A. Daily photoprotection to prevent photoaging. Photodermatol. Photoimmunol. Photomed. 2021 doi: 10.1111/phpp.12688. PubMed DOI

Neale R., Khan S., Lucas R., Waterhouse M., Whiteman D., Olsen C. The effect of sunscreen on vitamin D: A review. Br. J. Dermatol. 2019;181:907–915. doi: 10.1111/bjd.17980. PubMed DOI

Bikle D. Do sunscreens block vitamin D production? A critical review by an international panel of experts. Br. J. Dermatol. 2019;181:884. doi: 10.1111/bjd.18126. PubMed DOI PMC

Souto E.B., Fernandes A.R., Martins-Gomes C., Coutinho T.E., Durazzo A., Lucarini M., Souto S.B., Silva A.M., Santini A. Nanomaterials for skin delivery of cosmeceuticals and pharmaceuticals. Appl. Sci. 2020;10:1594. doi: 10.3390/app10051594. DOI

Dhapte-Pawar V., Kadam S., Saptarsi S., Kenjale P.P. Nanocosmeceuticals: Facets and aspects. Future Sci. OA. 2020;6:FSO613. doi: 10.2144/fsoa-2019-0109. PubMed DOI PMC

Cao M., Li B., Guo M., Liu Y., Zhang L., Wang Y., Hu B., Li J., Sutherland D.S., Wang L. In vivo percutaneous permeation of gold nanomaterials in consumer cosmetics: Implication in dermal safety assessment of consumer nanoproducts. Nanotoxicology. 2020;15:131–144. doi: 10.1080/17435390.2020.1860264. PubMed DOI

Beamer C.A. Mucosal Delivery of Drugs and Biologics in Nanoparticles. Springer; Berlin/Heidelberg, Germany: 2020. Toxicity of Nanomaterials to the Host and the Environment; pp. 233–245.

Sengupta J., Ghosh S., Datta P., Gomes A., Gomes A. Physiologically important metal nanoparticles and their toxicity. J. Nanosci. Nanotechnol. 2014;14:990–1006. doi: 10.1166/jnn.2014.9078. PubMed DOI

He Y., Zhang W., Guo T., Zhang G., Qin W., Zhang L., Wang C., Zhu W., Yang M., Hu X. Drug nanoclusters formed in confined nano-cages of CD-MOF: Dramatic enhancement of solubility and bioavailability of azilsartan. Acta Pharm. Sin. B. 2019;9:97–106. doi: 10.1016/j.apsb.2018.09.003. PubMed DOI PMC

Carnovale C., Bryant G., Shukla R., Bansal V. Identifying trends in gold nanoparticle toxicity and uptake: Size, shape, capping ligand, and biological corona. ACS Omega. 2019;4:242–256. doi: 10.1021/acsomega.8b03227. DOI

Ilić K., Hartl S., Galić E., Tetyczka C., Pem B., Barbir R., Milić M., Vrček I.V., Roblegg E., Pavičić I. Interaction of Differently Coated Silver Nanoparticles with Skin and Oral Mucosal Cells. J. Pharm. Sci. 2021;110:2250–2261. doi: 10.1016/j.xphs.2021.01.030. PubMed DOI

Guilger-Casagrande M., Germano-Costa T., Bilesky-José N., Pasquoto-Stigliani T., Carvalho L., Fraceto L.F., de Lima R. Influence of the capping of biogenic silver nanoparticles on their toxicity and mechanism of action towards Sclerotinia sclerotiorum. J. Nanobiotechnol. 2021;19:1–18. doi: 10.1186/s12951-021-00797-5. PubMed DOI PMC

Bengalli R., Colantuoni A., Perelshtein I., Gedanken A., Collini M., Mantecca P., Fiandra L. In vitro skin toxicity of CuO and ZnO nanoparticles: Application in the safety assessment of antimicrobial coated textiles. NanoImpact. 2021;21:100282. doi: 10.1016/j.impact.2020.100282. PubMed DOI

Hashempour S., Ghanbarzadeh S., Maibach H.I., Ghorbani M., Hamishehkar H. Skin toxicity of topically applied nanoparticles. Ther. Deliv. 2019;10:383–396. doi: 10.4155/tde-2018-0060. PubMed DOI

Electrospun Nanofibers Encapsulated with Natural Products: A Novel Strategy to Counteract Skin Aging