title: Multiscale fabrication of biomimetic scaffolds for tympanic membrane tissue engineering.
abstract: The tympanic membrane (TM) is a thin tissue able to efficiently collect and transmit sound vibrations across the middle ear thanks to the particular orientation of its collagen fibers, radiate on one side and circular on the opposite side. Through the combination of advanced scaffolds and autologous cells, tissue engineering (TE) could offer valuable alternatives to autografting in major TM lesions. In this study, a multiscale approach based on electrospinning (ES) and additive manufacturing (AM) was investigated to fabricate scaffolds, based on FDA approved copolymers, resembling the anatomic features and collagen fiber arrangement of the human TM. A single scale TM scaffold was manufactured using a custom-made collector designed to confer a radial macro-arrangement to poly(lactic-co-glycolic acid) electrospun fibers during their deposition. Dual and triple scale scaffolds were fabricated combining conventional ES with AM to produce poly(ethylene oxide terephthalate)/poly(butylene terephthalate) block copolymer scaffolds with anatomic-like architecture. The processing parameters were optimized for each manufacturing method and copolymer. TM scaffolds were cultured in vitro with human mesenchymal stromal cells, which were viable, metabolically active and organized following the anisotropic character of the scaffolds. The highest viability, cell density and protein content were detected in dual and triple scale scaffolds. Our findings showed that these biomimetic micro-patterned substrates enabled cell disposal along architectural directions, thus appearing as promising substrates for developing functional TM replacements via TE.
authors.affiliation: Laboratory of Temporal Bone Dissection and Otologic Tissue Engineering (OtoLab), Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, Pisa, Italy. Institute for Biomedical Technology & Technical Medicine (MIRA), Tissue Regeneration Department, University of Twente, Enschede, The Netherlands. Laboratory of Bioactive Polymeric Materials for Biomedical and Environmental Applications (BIOLab), Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy. Institute for Technology Inspired Regenerative Medicine (MERLN), Complex Tissue Regeneration Department, Maastricht University, Maastricht, The Netherlands.
authors.forename: Carlos
authors.initials: C
authors.lastname: Mota
authors.forename: Serena
authors.initials: S
authors.lastname: Danti
authors.forename: Delfo
authors.initials: D
authors.lastname: D'Alessandro
authors.forename: Luisa
authors.initials: L
authors.lastname: Trombi
authors.forename: Claudio
authors.initials: C
authors.lastname: Ricci
authors.forename: Dario
authors.initials: D
authors.lastname: Puppi
authors.forename: Dinuccio
authors.initials: D
authors.lastname: Dinucci
authors.forename: Mario
authors.initials: M
authors.lastname: Milazzo
authors.forename: Cesare
authors.initials: C
authors.lastname: Stefanini
authors.forename: Federica
authors.initials: F
authors.lastname: Chiellini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moroni
authors.forename: Stefano
authors.initials: S
authors.lastname: Berrettini
mesh_terms: D032701:Biomimetics; D001854:Bone Marrow Cells / Q000166:cytology; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014432:Tympanic Membrane / Q000033:anatomy & histology / Q000473:pathology
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid