Journal
BIOMATERIALS
Volume 52, Issue -, Pages 452-462Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.01.073
Keywords
Cartilage tissue engineering; Scaffold-free constructs; Custom culture wells; Tissue rings; Microspheres
Funding
- National Institutes of Health [R01AR063194, T32AR007505]
- Medtronic Foundation
- NSF IGERT [DGE 1144804]
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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-beta 1-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. (C) 2015 Elsevier Ltd. All rights reserved.
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