{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:39:47Z","timestamp":1788777587708,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della Salute","award":["08016518"],"award-info":[{"award-number":["08016518"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Ossiculoplasty is a surgical operation performed to restore auditory transmission through the reconstruction of the ossicular chain using prosthetics. Tissue bioengineering has assumed a pivotal role in implementing alternatives to conventional ossicular middle ear replacement prostheses, to overcome extrusion while preserving acoustic properties. This in vitro study aims to explore, for the first time in current literature, the feasibility of a biohybrid middle ear prosthesis, composed of titanium surrounded by a bone extracellular matrix as bio-coating. We have hereby studied the adhesion and proliferation of human adipose-derived mesenchymal stem cells (hASC) on titanium scaffolds in vitro. Moreover, we identified the osteogenic differentiation of hASC using an immunofluorescence assay to analyze osteoblasts\u2019 gene expression profiles (Alp, Runx2, Col1a1, Osx, and Bglap), and we counted the presence of collagen as a marker of hASC\u2019s ability to secrete an extracellular matrix. We utilized scanning electron microscopy to evaluate the presence of an extracellular matrix on the scaffolds. Our preliminary data demonstrated the titanium\u2019s ability to support human adipose-derived mesenchymal stem cell colonization, proliferation, and osteoblastic differentiation, in order to obtain a biohybrid device. Our experience seems encouraging; thus, we advocate for further in vivo research to corroborate our results regarding bone transplantation.<\/jats:p>","DOI":"10.3390\/jfb14120561","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T03:53:52Z","timestamp":1701230032000},"page":"561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Titanium Biohybrid Middle Ear Prostheses: A Preliminary In Vitro Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Mario","family":"Mosconi","sequence":"first","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Carlotto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7545-7337","authenticated-orcid":false,"given":"Laura","family":"Caliogna","sequence":"additional","affiliation":[{"name":"Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela","family":"Berni","sequence":"additional","affiliation":[{"name":"Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Gastaldi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy"},{"name":"Centre for Health Technologies, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1275-0653","authenticated-orcid":false,"given":"Michele","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Civil Engineering and Architecture (DICAr), University of Pavia, Via Ferrata 3, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6473-4482","authenticated-orcid":false,"given":"Alice Maria","family":"Brancato","sequence":"additional","affiliation":[{"name":"Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Bina","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Minervini","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Malpede","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Chiara","family":"Stellato","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-4570","authenticated-orcid":false,"given":"Francesco","family":"Lazzerini","sequence":"additional","affiliation":[{"name":"Otolaryngology, ENT Audiology and Phoniatrics Unit, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6900-1306","authenticated-orcid":false,"given":"Luca","family":"Bruschini","sequence":"additional","affiliation":[{"name":"Otolaryngology, ENT Audiology and Phoniatrics Unit, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Benazzo","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Canzi","sequence":"additional","affiliation":[{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Department of Otorhinolaryngology, University of Pavia, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/MAO.0000000000003772","article-title":"Ossicular chain reconstruction with titanium prostheses: A systematic review and meta-analysis","volume":"44","author":"Kortebein","year":"2023","journal-title":"Otol. Neurotol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"000348942311599","DOI":"10.1177\/00034894231159969","article-title":"Which is better for ossiculoplasty following tympanomastoidectomy: Polycel\u00ae or Titanium?","volume":"132","author":"Kim","year":"2023","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3567","DOI":"10.1007\/s00405-023-07849-6","article-title":"Comparison of partial vs. total ossicular chain reconstruction using titanium prosthesis: A retrospective cohort study","volume":"280","author":"Faramarzi","year":"2023","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.joto.2021.08.002","article-title":"FDA MAUDE database analysis of titanium middle ear prosthesis","volume":"17","author":"Carey","year":"2022","journal-title":"J. Otol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s12070-011-0472-7","article-title":"Ossiculoplasty: Revisited","volume":"65","author":"Mudhol","year":"2013","journal-title":"Ind. J. Otolaryngol. Head Neck Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1017\/S0022215114002023","article-title":"Long-term outcome of ossiculoplasty using autogenous mastoid cortical bone","volume":"128","author":"Yu","year":"2014","journal-title":"J. Laryngol. Otol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1007\/s12070-018-1369-5","article-title":"Comparison of Ossiculoplasty Using Autograft Ossicle Versus Allograft (Teflon)","volume":"71","author":"Hajela","year":"2019","journal-title":"Ind. J. Otolaryngol. Head Neck Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"708","DOI":"10.3109\/00016489.2011.556662","article-title":"Titanium versus non-titanium prostheses in ossiculoplasty: A meta-analysis","volume":"131","author":"Zhang","year":"2011","journal-title":"Acta Otolaryngol."},{"key":"ref_9","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_10","unstructured":"Sanna, M., Hiroshi, S., Mancini, F., Russo, A., Taibah, A., and Falcioni, M. (2018). Middle Ear and Mastoid Microsurgery, Thieme."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1067\/mhn.2001.120397","article-title":"Reconstruction of the Ossicular Chain with Titanium Implants","volume":"125","author":"Dalchow","year":"2001","journal-title":"Otolaryngol.-Head Neck Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1097\/MLG.0b013e31817bd807","article-title":"Titanium versus nontitanium prostheses in ossiculoplasty","volume":"118","author":"Coffey","year":"2008","journal-title":"Laryngoscope"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.anl.2020.11.019","article-title":"Limitations of non-echo planar diffusion weighted magnetic resonance imaging (non-EPI MRI) in cholesteatoma surveillance after ossicular chain reconstruction. A prospective study","volume":"48","author":"Liktor","year":"2021","journal-title":"Auris Nasus Larynx."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s10544-009-9293-9","article-title":"Novel biological\/biohybrid prostheses for the ossicular chain: Fabrication feasibility and preliminary functional characterization","volume":"11","author":"Danti","year":"2009","journal-title":"Biomed. Microdev."},{"key":"ref_15","first-page":"1343","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":"2009","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18284","DOI":"10.1038\/s41598-020-75385-y","article-title":"Osteogenic potential of human adipose derived stem cells (hASCs) seeded on titanium trabecular spinal cages","volume":"10","author":"Caliogna","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s40883-018-0064-0","article-title":"Physical stimulations for bone and cartilage regeneration","volume":"4","author":"Huang","year":"2018","journal-title":"Regen. Eng. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.14639\/0392-100X-suppl.1-43-2023-09","article-title":"Current trends on subtotal petrosectomy with cochlear implantation in recalcitrant chronic middle ear disorders","volume":"43","author":"Canzi","year":"2023","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"415","DOI":"10.5152\/iao.2022.21360","article-title":"Functional outcomes of single-stage ossiculoplasty in chronic otitis media with or without cholesteatoma","volume":"18","author":"Park","year":"2022","journal-title":"J. Int. Adv. Otol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/coa.12987","article-title":"Comparative study of new autologous material, bone-cartilage composite graft, for ossiculoplasty with Polycel\u00ae and Titanium","volume":"43","author":"Kong","year":"2018","journal-title":"Clin. Otolaryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/MAO.0b013e31826bf16d","article-title":"Allograft tympanoplasty: A historical perspective","volume":"34","author":"Farr","year":"2013","journal-title":"Otol. Neurotol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.anorl.2010.11.005","article-title":"Titanium ossicular chain replacement prostheses: Prognostic factors and preliminary functional results","volume":"128","author":"Mardassi","year":"2011","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Canzi, P., Carlotto, E., Bruschini, L., Minervini, D., Mosconi, M., Caliogna, L., Ottoboni, I., Chiapperini, C., Lazzerini, F., and Forli, F. (2023). Extrusion and Dislocation in Titanium Middle Ear Prostheses: A Literature Review. Brain Sci., 13.","DOI":"10.20944\/preprints202309.0912.v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s004050000300","article-title":"Closed tympanoplasty in cholesteatoma surgery: Long-term (10 Years) hearing results using cartilage ossiculoplasty","volume":"258","author":"Quaranta","year":"2001","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1016\/j.biomaterials.2008.02.025","article-title":"The influence of an in vitro generated bone-like extracellular matrix on osteoblastic gene expression of marrow stromal cells","volume":"29","author":"Pham","year":"2008","journal-title":"Biomaterials"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.bbrc.2016.01.112","article-title":"TIEG1 enhances Osterix expression and mediates its induction by TGF\u03b2 and BMP2 in osteoblasts","volume":"470","author":"Subramaniam","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"133","DOI":"10.4248\/BR201302003","article-title":"Osteogenesis of adipose-derived stem cells","volume":"1","author":"Grottkau","year":"2013","journal-title":"Bone Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1002\/jcp.26042","article-title":"The roles of signaling pathways in bne repair and regeneration","volume":"233","author":"Majidinia","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Barberi, J., and Spriano, S. (2021). Titanium and protein adsorption: An overview of mechanisms and effects of surface features. Materials, 14.","DOI":"10.3390\/ma14071590"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s12070-021-02634-5","article-title":"Current Application and Future Prospects of 3D Printing in Otorhinolaryngology\u2014A Narrative Review","volume":"74","author":"Tiwari","year":"2022","journal-title":"Ind. J. Otolaryngol. Head Neck Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6737345","DOI":"10.1155\/2016\/6737345","article-title":"Adipose-derived stem cells for tissue rngineering and regenerative medicine applications","volume":"2016","author":"Dai","year":"2016","journal-title":"Stem Cells Int."}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/14\/12\/561\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:33:09Z","timestamp":1760131989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/14\/12\/561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,29]]},"references-count":31,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["jfb14120561"],"URL":"https:\/\/doi.org\/10.3390\/jfb14120561","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,29]]}}}