{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:25:59Z","timestamp":1790141159594,"version":"4.0.1"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Combining multiple drugs or biologically active substances for wound healing could not only resist the formation of multidrug resistant pathogens, but also achieve better therapeutic effects. Herein, the hydrophobic fluoroquinolone antibiotic ciprofloxacin (CIP) and the hydrophilic broad-spectrum antibiotic tetracycline hydrochloride (TH) were introduced into the coaxial polycaprolactone\/gelatin (PCL\/GEL) nanofiber mat with CIP loaded into the PCL (core layer) and TH loaded into the GEL (shell layer), developing antibacterial wound dressing with the co-delivering of the two antibiotics (PCL-CIP\/GEL-TH). The nanostructure, physical properties, drug release, antibacterial property, and in vitro cytotoxicity were investigated accordingly. The results revealed that the CIP shows a long-lasting release of five days, reaching the releasing rate of 80.71%, while the cumulative drug release of TH reached 83.51% with a rapid release behavior of 12 h. The in vitro antibacterial activity demonstrated that the coaxial nanofiber mesh possesses strong antibacterial activity against E. coli and S. aureus. In addition, the coaxial mats showed superior biocompatibility toward human skin fibroblast cells (hSFCs). This study indicates that the developed PCL-CIP\/GEL-TH nanofiber membranes hold enormous potential as wound dressing materials.<\/jats:p>","DOI":"10.3390\/ijms23031895","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T23:37:48Z","timestamp":1644363468000},"page":"1895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Synergistic Effect of Co-Delivering Ciprofloxacin and Tetracycline Hydrochloride for Promoted Wound Healing by Utilizing Coaxial PCL\/Gelatin Nanofiber Membrane"],"prefix":"10.3390","volume":"23","author":[{"given":"Mengxia","family":"Lin","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control Technology, College of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control Technology, College of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control Technology, College of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7892-7381","authenticated-orcid":false,"given":"Dan","family":"Xia","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control Technology, College of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyong","family":"Liang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control Technology, College of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruodan","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/j.1524-475X.2009.00543.x","article-title":"Human skin wounds: A major and snowballing threat to public health and the economy","volume":"17","author":"Sen","year":"2009","journal-title":"Wound Repair Regen."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Akita, S. (2019). Wound Repair and Regeneration: Mechanisms, Signaling. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246328"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1080\/01926230701584189","article-title":"Novel Insights into Wound Healing Sequence of Events","volume":"35","author":"Solomonik","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s12325-017-0478-y","article-title":"Chronic Wound Healing: A Review of Current Management and Treatments","volume":"34","author":"Han","year":"2017","journal-title":"Adv. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"115839","DOI":"10.1016\/j.carbpol.2020.115839","article-title":"Wound healing and antimicrobial effect of active secondary metabolites in chitosan-based wound dressings: A review","volume":"233","author":"Moeini","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12905","DOI":"10.1021\/acsnano.0c03855","article-title":"Synthetic Polymeric Antibacterial Hydrogel for Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing: Nanoantimicrobial Self-Assembly, Drug- and Cytokine-Free Strategy","volume":"14","author":"Liu","year":"2020","journal-title":"ACS Nano"},{"key":"ref_7","first-page":"721","article-title":"Bioactive antiinflammatory antibacterial hemostatic citrate-based dressing with macrophage polarization regulation for accelerating wound healing and hair follicle neogenesis","volume":"6","author":"Liu","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jiph.2016.08.007","article-title":"Antibiotic resistance","volume":"10","author":"Frieri","year":"2017","journal-title":"J. Infect. Public Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112","DOI":"10.21037\/atm.2019.12.91","article-title":"Increased multidrug resistant isolates: New clinical burdens for 66 hospitals in Shanghai, 2015 to 2017","volume":"8","author":"Lin","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.addr.2015.10.022","article-title":"Recent advances of cocktail chemotherapy by combination drug delivery systems","volume":"98","author":"Hu","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.addr.2014.10.027","article-title":"Therapeutic strategies to combat antibiotic resistance","volume":"78","author":"Brooks","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/j.burns.2015.03.013","article-title":"Biodegradable soy wound dressings with controlled release of antibiotics: Results from a guinea pig burn model","volume":"41","author":"Egozi","year":"2015","journal-title":"Burns"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.ejps.2012.08.006","article-title":"Antibacterial fluoroquinolone antibiotic-containing fibrous materials from poly(l-lactide-co-d,l-lactide) prepared by electrospinning","volume":"47","author":"Toncheva","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.ijbiomac.2018.12.085","article-title":"Evaluation of electrospun poly (vinyl alcohol)-based nanofiber mats incorporated with Zataria multiflora essential oil as potential wound dressing","volume":"125","author":"Ardekani","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jconrel.2015.10.049","article-title":"Nanoparticles and nanofibers for topical drug delivery","volume":"240","author":"Goyal","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s13770-017-0075-9","article-title":"Electrospun Collagen Nanofibers and Their Applications in Skin Tissue Engineering","volume":"14","author":"Law","year":"2017","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"885","DOI":"10.2147\/IJN.S78675","article-title":"Sustained release of vancomycin from novel biodegradable nanofiber-loaded vascular prosthetic grafts: In vitro and in vivo study","volume":"10","author":"Liu","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1007\/s10856-010-4048-y","article-title":"Electro-spinning of PLGA\/PCL blends for tissue engineering and their biocompatibility","volume":"21","author":"Nguyen","year":"2010","journal-title":"J. Mater. Sci.-Mater. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"37381","DOI":"10.1021\/acsami.9b07053","article-title":"Triple PLGA\/PCL Scaffold Modification Including Silver Impregnation, Collagen Coating, and Electrospinning Significantly Improve Biocompatibility, Antimicrobial, and Osteogenic Properties for Orofacial Tissue Regeneration","volume":"11","author":"Qian","year":"2019","journal-title":"Acs Appl. Mater. Interfaces"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.biomaterials.2016.11.018","article-title":"Three dimensional electrospun PCL\/PLA blend nanofibrous scaffolds with significantly improved stem cells osteogenic differentiation and cranial bone formation","volume":"115","author":"Yao","year":"2017","journal-title":"Biomaterials"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.msec.2019.109768","article-title":"Smart electrospun nanofibers containing PCL\/gelatin\/graphene oxide for application in nerve tissue engineering","volume":"103","author":"Heidari","year":"2019","journal-title":"Mater. Sci. Eng. C-Mater. Biol. Appl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s42242-020-00095-3","article-title":"Fabrication and characterization of 3D printed biocomposite scaffolds based on PCL and zirconia nanoparticles","volume":"4","author":"Wang","year":"2021","journal-title":"Bio-Des. Manuf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.msec.2016.10.083","article-title":"Electrospun polycaprolactone\/gelatin composites with enhanced cell-matrix interactions as blood vessel endothelial layer scaffolds","volume":"71","author":"Jiang","year":"2017","journal-title":"Mater. Sci. Eng. C-Mater. Biol. Appl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1039\/C4CS00226A","article-title":"Electrosprayed nanoparticles and electrospun nanofibers based on natural materials: Applications in tissue regeneration, drug delivery and pharmaceuticals","volume":"44","author":"Sridhar","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ejps.2018.07.002","article-title":"Fast dissolving drug delivery membrane based on the ultra-thin shell of electrospun core-shell nanofibers","volume":"122","author":"Li","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pant, B., Park, M., and Park, S.J. (2019). Drug Delivery Applications of Core-Sheath Nanofibers Prepared by Coaxial Electrospinning: A Review. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11070305"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.addr.2016.04.019","article-title":"Poly(lactic acid) nanofibrous scaffolds for tissue engineering","volume":"107","author":"Santoro","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ijpharm.2019.118590","article-title":"Novel lavender oil and silver nanoparticles simultaneously loaded onto polyurethane nanofibers for wound-healing applications","volume":"569","author":"Sofi","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/adfm.202170042","article-title":"Nanogel Encapsulated Hydrogels As Advanced Wound Dressings for the Controlled Delivery of Antibiotics","volume":"31","author":"Fan","year":"2021","journal-title":"Adv. Funct. Mater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1800299","DOI":"10.1002\/adfm.201800299","article-title":"Rapid Sterilization and Accelerated Wound Healing Using Zn2+ and Graphene Oxide Modified g-C3N4 under Dual Light Irradiation","volume":"28","author":"Li","year":"2018","journal-title":"Adv. Funct. Mater."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"128805","DOI":"10.1016\/j.cej.2021.128805","article-title":"Rapid bacteria capturing and killing by AgNPs\/N-CD@ZnO hybrids strengthened photo-responsive xerogel for rapid healing of bacteria-infected wounds","volume":"414","author":"Huang","year":"2021","journal-title":"Chem. Eng. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1002\/mabi.201600108","article-title":"Electrospun Gelatin Fibers with a Multiple Release of Antibiotics Accelerate Dermal Regeneration in Infected Deep Burns","volume":"16","author":"Chen","year":"2016","journal-title":"Macromol. Biosci."},{"key":"ref_33","first-page":"12","article-title":"Evaluation of sustained ciprofloxacin release of biodegradable electrospun gelatin\/poly(glycerol sebacate) mat membranes for wound dressing applications","volume":"13","author":"Najafabadi","year":"2018","journal-title":"Asia-Pac. J. Chem. Eng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.carbpol.2013.01.059","article-title":"Antimicrobial electrospun membranes of chitosan\/poly(ethylene oxide) incorporating poly(hexamethylene biguanide) hydrochloride","volume":"94","author":"Dilamian","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1088\/0957-4484\/17\/9\/041","article-title":"Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs","volume":"17","author":"Taepaiboon","year":"2006","journal-title":"Nanotechnology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/mabi.200900168","article-title":"The Development of Genipin-Crosslinked Poly(caprolactone) (PCL)\/Gelatin Nanofibers for Tissue Engineering Applications","volume":"10","author":"Kim","year":"2010","journal-title":"Macromol. Biosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cej.2020.126518","article-title":"Exploiting synergistic effect of externally loaded bFGF and endogenous growth factors for accelerated wound healing using heparin functionalized PCL\/gelatin co-spun nanofibrous patches","volume":"404","author":"Joshi","year":"2021","journal-title":"Chem. Eng. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9988","DOI":"10.1021\/acsami.8b01855","article-title":"Estradiol-Loaded Poly(epsilon-caprolactone)\/Silk Fibroin Electrospun Microfibers Decrease Osteoclast Activity and Retain Osteoblast Function","volume":"10","author":"Steffi","year":"2018","journal-title":"Acs Appl. Mater. Interfaces"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ijpharm.2021.120313","article-title":"Fabrication of ciprofloxacin-loaded chitosan\/polyethylene oxide\/silica nanofibers for wound dressing application: In vitro and in vivo evaluations","volume":"597","author":"Hashemikia","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Uhljar, L.E., Kan, S.Y., Radacsi, N., Koutsos, V., Szabo-Revesz, P., and Ambrus, R. (2021). In Vitro Drug Release, Permeability, and Structural Test of Ciprofloxacin-Loaded Nanofibers. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13040556"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ejpb.2021.02.009","article-title":"Controlled release of tetracycline hydrochloride from poly (omega-pentadecalactone-co-epsilon-caprolactone)\/gelatin nanofibers","volume":"162","author":"Turan","year":"2021","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"43188","DOI":"10.1021\/acsami.9b15219","article-title":"Electrospun Polymer Composite Membrane with Superior Thermal Stability and Excellent Chemical Resistance for High-Efficiency PM2.5 Capture","volume":"11","author":"Yang","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jcis.2020.05.081","article-title":"Polyacrylonitrile\/polyimide composite sub-micro fibrous membranes for precise filtration of PM0.26 pollutants","volume":"578","author":"Zhou","year":"2020","journal-title":"J. Colloid Interface Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.pmatsci.2016.09.006","article-title":"Advances in electrospun skin substitutes","volume":"84","author":"Dias","year":"2016","journal-title":"Prog. Mater. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"22142","DOI":"10.1021\/acsami.1c00798","article-title":"Rayleigh Instability-Driven Coaxial Spinning of Knotted Cell-Laden Alginate Fibers as Artificial Lymph Vessels","volume":"13","author":"Majidi","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s10965-020-02265-4","article-title":"Biodegradable poly(lactic acid)\/poly(butylene succinate) Nanofibrous membrane with Core-shell structure and high density for improved mechanical properties","volume":"27","author":"Huang","year":"2020","journal-title":"J. Polym. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Keshvardoostchokami, M., Majidi, S.S., Huo, P., Ramachandran, R., Chen, M., and Liu, B. (2021). Electrospun Nanofibers of Natural and Synthetic Polymers as Artificial Extracellular Matrix for Tissue Engineering. Nanomaterials, 11.","DOI":"10.3390\/nano11010021"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.progpolymsci.2011.05.003","article-title":"Current research on the blends of natural and synthetic polymers as new biomaterials: Review","volume":"36","author":"Sionkowska","year":"2011","journal-title":"Prog. Polym. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1515\/ntrev-2020-0105","article-title":"Degradable tough chitosan dressing for skin wound recovery","volume":"9","author":"Kong","year":"2020","journal-title":"Nanotechnol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.msec.2015.02.015","article-title":"Hydrophilic PCU scaffolds prepared by grafting PEGMA and immobilizing gelatin to enhance cell adhesion and proliferation","volume":"50","author":"Shi","year":"2015","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.apsusc.2019.02.189","article-title":"Investigations on the antimicrobial activity and wound healing potential of ZnO nanoparticles","volume":"479","author":"Kaushik","year":"2019","journal-title":"Appl. Surf. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1177\/0885328217749962","article-title":"Core-shell poly(lactide-co-epsilon-caprolactone)-gelatin fiber scaffolds as pH-sensitive drug delivery systems","volume":"32","author":"Sang","year":"2018","journal-title":"J. Biomater. Appl."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1469-0691.2007.01946.x","article-title":"Associated antimicrobial resistance in Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes","volume":"14","author":"Wimmerstedt","year":"2008","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.ijbiomac.2018.09.122","article-title":"Preparation of biocompatible wound dressings with long-term antimicrobial activity through covalent bonding of antibiotic agents to natural polymers","volume":"123","author":"Hu","year":"2019","journal-title":"Int. J. Biol. Macromol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1895\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:15:59Z","timestamp":1760134559000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,8]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031895"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031895","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,8]]}}}