Generating Mechanically Stable, Pediatric, and Scaffold-Free Nasal Cartilage Constructs In Vitro.
Traditional methods of cartilage tissue engineering rely on the use of scaffolds. Although successful chondrogenesis has been reported in scaffold-based constructs, the use of exogenous materials has limited their application due to eliciting host immunogenic responses and potentially resulting in construct failure. As a result, tissue engineering approaches, which aim to generate scaffold-free cartilaginous constructs, have become of particular interest. Here, we generated stable three-dimensional scaffold-free cartilaginous constructs by cultivating expanded pediatric nasal chondrocyte multilayers in a slow turning lateral vessel bioreactor system under chemically defined media. Bioreactor cultivation resulted in increased construct cellularity, fourfold tissue thickness, and 200% sulfated glycosaminoglycan deposition with respect to static culture equivalent cultures. These improvements led to significantly enhanced mechanical and biochemical properties of bioreactor-cultivated constructs, allowing them to support their own weight, while static culture constructs remained fragile. Consequently, bioreactor-cultivated constructs closely resembled native nasal cartilage tissue histologically, mechanically, and biochemically. We propose that this method of cartilage construct formation could be used to obtain readily available human scaffold-free cartilaginous constructs.
1 Program in Developmental and Stem Cell Biology, Research Institute , Hospital for Sick Children, Toronto, Ontario, Canada .
Pedram
P
Akbari
2 Department of Chemical Engineering, Ryerson University , Toronto, Ontario, Canada .|3 Institute for Biomedical Engineering, Science and Technology, Ryerson University and St. Michael's Hospital , Toronto, Ontario, Canada .
Stephen D
SD
Waldman
4 Department of Otolaryngology-Head and Neck Surgery, Hospital for Sick Children, University of Toronto , Toronto, Ontario, Canada .
Evan J
EJ
Propst
4 Department of Otolaryngology-Head and Neck Surgery, Hospital for Sick Children, University of Toronto , Toronto, Ontario, Canada .
Sharon L
SL
Cushing
3 Institute for Biomedical Engineering, Science and Technology, Ryerson University and St. Michael's Hospital , Toronto, Ontario, Canada .
Joanna F
JF
Weber
1 Program in Developmental and Stem Cell Biology, Research Institute , Hospital for Sick Children, Toronto, Ontario, Canada .
Herman
H
Yeger
1 Program in Developmental and Stem Cell Biology, Research Institute , Hospital for Sick Children, Toronto, Ontario, Canada .
Walid A
WA
Farhat
D000293:Adolescent; D019149:Bioreactors; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002648:Child; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis / Q000502:physiology*; D004425:Ear Cartilage / Q000166:cytology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D055171:Nasal Cartilages / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
bioreactor; cartilage; human; nasal; scaffold free