title: Engineered cartilaginous tubes for tracheal tissue replacement via self-assembly and fusion of human mesenchymal stem cell constructs.
abstract: There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted into a small animal model for airway defects. The modular, bottom up approach used to grow stem cell-based cartilaginous tubes in this report is a promising platform to engineer complex organs (e.g., trachea), with control over tissue size and geometry, and has the potential to be used to generate autologous tissue implants for human clinical applications.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA.
authors.forename: Anna D
authors.initials: AD
authors.lastname: Dikina
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Rd., Worcester, MA 01609, USA.
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Strobel
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Lai
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Rd., Worcester, MA 01609, USA.
authors.forename: Marsha W
authors.initials: MW
authors.lastname: Rolle
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA; Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA. Electronic address: eben.alsberg@case.edu.
authors.forename: Eben
authors.initials: E
authors.lastname: Alsberg
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001696:Biomechanical Phenomena; D002356:Cartilage / Q000737:chemistry* / Q000166:cytology; D020219:Chondrogenesis; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008863:Microspheres; D011108:Polymers / Q000737:chemistry; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014132:Trachea / Q000473:pathology* / Q000637:transplantation*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D053773:Transforming Growth Factor beta1; D005780:Gelatin
keywords: Cartilage tissue engineering; Custom culture wells; Microspheres; Scaffold-free constructs; Tissue rings
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