{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T13:53:37Z","timestamp":1774706017697,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["ERA-NET cofund, EuroNanoMed III, project 4NanoEARDRM"],"award-info":[{"award-number":["ERA-NET cofund, EuroNanoMed III, project 4NanoEARDRM"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["B56H18000140001"],"award-info":[{"award-number":["B56H18000140001"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["OND1365231"],"award-info":[{"award-number":["OND1365231"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Chitin nanofibrils (CNs) are an emerging bio-based nanomaterial. Due to nanometric size and high crystallinity, CNs lose the allergenic features of chitin and interestingly acquire anti-inflammatory activity. Here we investigate the possible advantageous use of CNs in tympanic membrane (TM) scaffolds, as they are usually implanted inside highly inflamed tissue environment due to underlying infectious pathologies. In this study, the applications of CNs in TM scaffolds were twofold. A nanocomposite was used, consisting of poly(ethylene oxide terephthalate)\/poly(butylene terephthalate) (PEOT\/PBT) copolymer loaded with CN\/polyethylene glycol (PEG) pre-composite at 50\/50 (w\/w %) weight ratio, and electrospun into fiber scaffolds, which were coated by CNs from crustacean or fungal sources via electrospray. The degradation behavior of the scaffolds was investigated during 4 months at 37 \u00b0C in an otitis-simulating fluid. In vitro tests were performed using cell types to mimic the eardrum, i.e., human mesenchymal stem cells (hMSCs) for connective, and human dermal keratinocytes (HaCaT cells) for epithelial tissues. HMSCs were able to colonize the scaffolds and produce collagen type I. The inflammatory response of HaCaT cells in contact with the CN-coated scaffolds was investigated, revealing a marked downregulation of the pro-inflammatory cytokines. CN-coated PEOT\/PBT\/(CN\/PEG 50:50) scaffolds showed a significant indirect antimicrobial activity.<\/jats:p>","DOI":"10.3390\/pharmaceutics13091440","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T21:48:01Z","timestamp":1631483281000},"page":"1440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Chitin Nanofibril Application in Tympanic Membrane Scaffolds to Modulate Inflammatory and Immune Response"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-8537","authenticated-orcid":false,"given":"Serena","family":"Danti","sequence":"first","affiliation":[{"name":"Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121 Firenze, Italy"},{"name":"Department of Civil and Industrial Engineering, University of Pisa, 56122 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-2039","authenticated-orcid":false,"given":"Shivesh","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahareh","family":"Azimi","sequence":"additional","affiliation":[{"name":"Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121 Firenze, Italy"},{"name":"Department of Civil and Industrial Engineering, University of Pisa, 56122 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-5544","authenticated-orcid":false,"given":"Mario","family":"Milazzo","sequence":"additional","affiliation":[{"name":"Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121 Firenze, Italy"},{"name":"The BioRobotics Institute, Scuola Superiore Sant\u2019Anna, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2641-1070","authenticated-orcid":false,"given":"Alessandra","family":"Fusco","sequence":"additional","affiliation":[{"name":"Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121 Firenze, Italy"},{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Ricci","sequence":"additional","affiliation":[{"name":"Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121 Firenze, Italy"},{"name":"Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2900-2694","authenticated-orcid":false,"given":"Lorenzo","family":"Zavagna","sequence":"additional","affiliation":[{"name":"Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121 Firenze, Italy"},{"name":"Linari Engineering s.r.l., 56121 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Linari","sequence":"additional","affiliation":[{"name":"Linari Engineering s.r.l., 56121 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3087-1240","authenticated-orcid":false,"given":"Giovanna","family":"Donnarumma","sequence":"additional","affiliation":[{"name":"Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121 Firenze, Italy"},{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9463-1502","authenticated-orcid":false,"given":"Andrea","family":"Lazzeri","sequence":"additional","affiliation":[{"name":"Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121 Firenze, Italy"},{"name":"Department of Civil and Industrial Engineering, University of Pisa, 56122 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1298-6025","authenticated-orcid":false,"given":"Lorenzo","family":"Moroni","sequence":"additional","affiliation":[{"name":"Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5935-6245","authenticated-orcid":false,"given":"Carlos","family":"Mota","sequence":"additional","affiliation":[{"name":"Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Berrettini","sequence":"additional","affiliation":[{"name":"Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121 Firenze, Italy"},{"name":"Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"ref_1","first-page":"101","article-title":"Structure and function of the tympanic membrane: A review","volume":"49","author":"Lim","year":"1995","journal-title":"Acta Otorhinolaryngol. Belg."},{"key":"ref_2","first-page":"Doc09","article-title":"Passive and active middle ear implants","volume":"8","author":"Beutner","year":"2009","journal-title":"GMS Curr. Top. Otorhinolaryngol. Head Neck Surg."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Monasta, L., Ronfani, L., Marchetti, F., Montico, M., Vecchi Brumatti, L., Bavcar, A., Grasso, D., Barbiero, C., and Tamburlini, G. (2012). Burden of disease caused by otitis media: Systematic review and global estimates. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036226"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/01.mao.0000176177.17636.53","article-title":"Determinants of hearing loss in perforations of the tympanic membrane","volume":"27","author":"Mehta","year":"2006","journal-title":"Otol. Neurotol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1055\/s-0030-1261960","article-title":"Tympanic membrane reconstruction with non-autogenous transplants and alloplastic materials","volume":"89","author":"Kaftan","year":"2010","journal-title":"Laryngo-Rhino-Otol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"025005","DOI":"10.1088\/1758-5090\/7\/2\/025005","article-title":"Multiscale fabrication of biomimetic scaffolds for tympanic membrane tissue engineering","volume":"7","author":"Mota","year":"2015","journal-title":"Biofabrication"},{"key":"ref_7","unstructured":"Moo-Young, M. (2019). Ear Tissue Engineering. Comprehensive Biotechnology, Elsevier. [3rd ed.]."},{"key":"ref_8","first-page":"1","article-title":"Mimicking the Human Tympanic Membrane: The Significance of Scaffold Geometry","volume":"2002082","author":"Anand","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Moscato, S., Rocca, A., D\u2019Alessandro, D., Puppi, D., Gramigna, V., Milazzo, M., Stefanini, C., Chiellini, F., Petrini, M., and Berrettini, S. (2020). Tympanic Membrane Collagen Expression by Dynamically Cultured Human Mesenchymal Stromal Cell\/Star-Branched Poly (\u03b5-Caprolactone) Nonwoven Constructs. Appl. Sci., 10.","DOI":"10.3390\/app10093043"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3109\/21695717.2015.1092372","article-title":"Tissue engineering of the tympanic membrane using electrospun PEOT\/PBT copolymer scaffolds: A morphological in vitro study","volume":"13","author":"Danti","year":"2015","journal-title":"Hear. Balanc. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1007\/s13346-020-00736-1","article-title":"Ciprofloxacin-loaded polymeric nanoparticles incorporated electrospun fibers for drug delivery in tissue engineering applications","volume":"10","author":"Anand","year":"2020","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0030-6665(05)70332-7","article-title":"Biomaterials for implantable middle ear hearing devices","volume":"34","author":"Dormer","year":"2001","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Danti, S., Trombi, L., Fusco, A., Azimi, B., Lazzeri, A., Morganti, P., Coltelli, M.-B., and Donnarumma, G. (2019). Chitin nanofibrils and nanolignin as functional agents in skin regeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112669"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"121","DOI":"10.6000\/1927-3037.2016.05.04.1","article-title":"Circular economy: A new horizon for bio-nanocomposites from waste materials","volume":"5","author":"Morganti","year":"2016","journal-title":"Int. J. Biotechnol. Wellness Ind."},{"key":"ref_15","first-page":"61","article-title":"Antibacterial and anti-inflammatory green nanocomposites","volume":"47","author":"Morganti","year":"2016","journal-title":"Chem. Eng. Trans."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/02648725.2010.10648156","article-title":"Structure and function of enzymes acting on chitin and chitosan","volume":"27","author":"Hoell","year":"2010","journal-title":"Biotechnol. Genet. Eng. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.carbpol.2014.02.090","article-title":"Wet spinning of fibers made of chitosan and chitin nanofibrils","volume":"108","author":"Yudin","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1177\/0021955X11402549","article-title":"Fabrication and characterization of melt-blended polylactide-chitin composites and their foams","volume":"47","author":"Rizvi","year":"2011","journal-title":"J. Cell. Plast."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.compositesa.2015.05.024","article-title":"Plasticized polylactic acid nanocomposite films with cellulose and chitin nanocrystals prepared using extrusion and compression molding with two cooling rates: Effects on mechanical, thermal and optical properties","volume":"83","author":"Herrera","year":"2016","journal-title":"Compos. Part A Appl. Sci. Manuf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.matdes.2015.12.083","article-title":"Functionalized blown films of plasticized polylactic acid\/chitin nanocomposite: Preparation and characterization","volume":"92","author":"Herrera","year":"2016","journal-title":"Mater. Des."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Herrera, N., Singh, A.A., Salaberria, A.M., Labidi, J., Mathew, A.P., and Oksman, K. (2017). Triethyl citrate (TEC) as a dispersing aid in polylactic acid\/chitin nanocomposites prepared via liquid-assisted extrusion. Polymers, 9.","DOI":"10.3390\/polym9090406"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1007\/s10570-017-1216-y","article-title":"Homogeneous dispersion of chitin nanofibers in polylactic acid with different pretreatment methods","volume":"24","author":"Li","year":"2017","journal-title":"Cellulose"},{"key":"ref_23","first-page":"42","article-title":"Effect of surface acetylated-chitin nanocrystals on structure and mechanical properties of poly (lactic acid)","volume":"131","author":"Zhang","year":"2014","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Coltelli, M.-B., Cinelli, P., Gigante, V., Aliotta, L., Morganti, P., Panariello, L., and Lazzeri, A. (2019). Chitin nanofibrils in poly (lactic acid) (PLA) nanocomposites: Dispersion and thermo-mechanical properties. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030504"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Morganti, P., Fusco, A., Paoletti, I., Perfetto, B., Del Ciotto, P., Palombo, M., Chianese, A., Baroni, A., and Donnarumma, G. (2017). Anti-inflammatory, immunomodulatory, and tissue repair activity on human keratinocytes by green innovative nanocomposites. Materials, 10.","DOI":"10.3390\/ma10070843"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9335","DOI":"10.1016\/S0032-3861(01)00453-0","article-title":"Poly (ethylene oxide)\/poly (butylene terephthalate) segmented block copolymers: The effect of copolymer composition on physical properties and degradation behavior","volume":"42","author":"Deschamps","year":"2001","journal-title":"Polymer"},{"key":"ref_27","first-page":"329","article-title":"New alloplastic tympanic membrane material","volume":"12","author":"Grote","year":"1991","journal-title":"Am. J. Otol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0142-9612(03)00495-2","article-title":"In vivo and in vitro degradation of poly (ether ester) block copolymers based on poly (ethylene glycol) and poly (butylene terephthalate)","volume":"25","author":"Deschamps","year":"2004","journal-title":"Biomaterials"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Azimi, B., Ricci, C., Fusco, A., Zavagna, L., Linari, S., Donnarumma, G., Hadrich, A., Cinelli, P., Coltelli, M.-B., and Danti, S. (2021). Electrosprayed Shrimp and Mushroom Nanochitins on Cellulose Tissue for Skin Contact Application. Molecules, 26.","DOI":"10.3390\/molecules26144374"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Azimi, B., Thomas, L., Fusco, A., Kalaoglu-Altan, O.I., Basnett, P., Cinelli, P., De Clerck, K., Roy, I., Donnarumma, G., and Coltelli, M.-B. (2020). Electrosprayed chitin nanofibril\/electrospun polyhydroxyalkanoate fiber mesh as functional nonwoven for skin application. J. Funct. Biomater., 11.","DOI":"10.3390\/jfb11030062"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1002\/lary.25102","article-title":"Effect of p H and oxygen on biofilm formation in acute otitis media associated NTH i clinical isolates","volume":"125","author":"Osgood","year":"2015","journal-title":"Laryngoscope"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1017\/S0022215100074703","article-title":"Long term results of middle ear reconstructive surgery","volume":"85","author":"Thorburn","year":"1971","journal-title":"J. Laryngol. Otol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"103541","DOI":"10.1016\/j.jmbbm.2019.103541","article-title":"De novo topology optimization of Total Ossicular Replacement Prostheses","volume":"103","author":"Milazzo","year":"2020","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/jbm.a.32447","article-title":"Development of tissue-engineered substitutes of the ear ossicles: PORP-shaped poly (propylene fumarate)-based scaffolds cultured with human mesenchymal stromal cells","volume":"92","author":"Danti","year":"2010","journal-title":"J. Biomed. Mater. Res.-Part A"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.clindermatol.2008.01.003","article-title":"Chitin nanofibrils for advanced cosmeceuticals","volume":"26","author":"Morganti","year":"2008","journal-title":"Clin. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.coi.2019.11.004","article-title":"Epithelial cells: Liaisons of immunity","volume":"62","author":"Larsen","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1081\/MC-120018022","article-title":"Formation of co-continuous structures in melt-mixed immiscible polymer blends","volume":"43","author":"Paul","year":"2003","journal-title":"J. Macromol. Sci.-Polym. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.carbpol.2014.06.043","article-title":"Rheological study of chitosan acetate solutions containing chitin nanofibrils","volume":"112","author":"Tishchenko","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Joseph, B., Mavelil Sam, R., Balakrishnan, P., Maria, H.J., Gopi, S., Volova, T., Fernandes, S.C.M., and Thomas, S. (2020). Extraction of Nanochitin from Marine Resources and Fabrication of Polymer Nanocomposites: Recent Advances. Polymers, 12.","DOI":"10.3390\/polym12081664"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, M., Xue, H., Feng, Z., Cheng, B., and Yang, H. (2017). Increase of tensile strength and toughness of bio-based diglycidyl ether of bisphenol A with chitin nanowhiskers. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177673"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.compositesa.2018.10.028","article-title":"Mechanical reinforcement and thermal properties of PVA tricomponent nanocomposites with chitin nanofibers and cellulose nanocrystals","volume":"116","author":"Irvin","year":"2019","journal-title":"Compos. Part A Appl. Sci. Manuf."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.carbpol.2018.03.074","article-title":"Effect of chitin nanofibrils on electrospinning of chitosan-based composite nanofibers","volume":"194","author":"Dobrovolskaya","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.carbpol.2013.09.012","article-title":"Electrospinning and characterization of chitin nanofibril\/polycaprolactone nanocomposite fiber mats","volume":"101","author":"Ji","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1901287","DOI":"10.1002\/adhm.201901287","article-title":"Electrospinning piezoelectric fibers for biocompatible devices","volume":"9","author":"Azimi","year":"2020","journal-title":"Adv. Healthc. Mater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1177\/00034894760850S221","article-title":"Biochemical characteristics of middle ear effusions","volume":"85","author":"Juhn","year":"1976","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1097\/00005537-200201000-00027","article-title":"Compositional difference in middle ear effusion: Mucous versus serous","volume":"112","author":"Chung","year":"2002","journal-title":"Laryngoscope"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0385-8146(00)00097-3","article-title":"Serous or mucoid effusion in the course of secretory otitis media: Influence of ion transport modulation","volume":"28","author":"Portier","year":"2001","journal-title":"Auris Nasus Larynx"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1001\/archotol.1990.01870010058017","article-title":"Lysozyme levels in middle ear effusion and serum in otitis media","volume":"116","author":"Harada","year":"1990","journal-title":"Arch. Otolaryngol. Neck Surg."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jones, M., Kujundzic, M., John, S., and Bismarck, A. (2020). Crab vs. Mushroom: A review of crustacean and fungal chitin in wound treatment. Mar. Drugs, 18.","DOI":"10.3390\/md18010064"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1007\/s10856-007-0127-0","article-title":"Gelatine\/PLLA sponge-like scaffolds: Morphological and biological characterization","volume":"8","author":"Lazzeri","year":"2007","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1021\/bm200248h","article-title":"Effect of electrospun fiber diameter and alignment on macrophage activation and secretion of proinflammatory cytokines and chemokines","volume":"12","author":"Saino","year":"2011","journal-title":"Biomacromolecules"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"De la Ossa, J.G., Fusco, A., Azimi, B., Esposito Salsano, J., Digiacomo, M., Coltelli, M.-B., De Clerck, K., Roy, I., Macchia, M., and Lazzeri, A. (2021). Immunomodulatory Activity of electrospun polyhydroxyalkanoate fiber scaffolds incorporating olive leaf extract. Appl. Sci., 11.","DOI":"10.3390\/app11094006"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1006\/cyto.2001.0946","article-title":"Regulation and role of interleukin 6 in wounded human epithelial keratinocytes","volume":"15","author":"Sugawara","year":"2001","journal-title":"Cytokine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/0003489492101S1006","article-title":"Immunologic characteristics of cytokines in otitis media with effusion","volume":"101","author":"Himi","year":"1992","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1111\/j.1469-0691.2010.03083.x","article-title":"High cytokine levels in perforated acute otitis media exudates containing live bacteria","volume":"16","author":"Skovbjerg","year":"2010","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.autrev.2005.03.006","article-title":"Transforming growth factor beta (TGF-beta) and autoimmunity","volume":"4","author":"Aoki","year":"2005","journal-title":"Autoimmun Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S1357-2725(99)00013-8","article-title":"Human beta-defensin-2","volume":"31","author":"Harder","year":"1999","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fcimb.2016.00194","article-title":"Antimicrobial peptides: An emerging category of therapeutic agents","volume":"6","author":"Mahlapuu","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"18016","DOI":"10.1038\/natrevmats.2018.16","article-title":"Nanofibrils in nature and materials engineering","volume":"3","author":"Ling","year":"2018","journal-title":"Nat. Rev. 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