Overcoming Challenges in Engineering Large, Scaffold-Free Neocartilage with Functional Properties

Although numerous cartilage engineering methods have been described, few report generation of constructs greater than 4 cm 2 , which is the typical lesion size considered for cell-based therapies. Furthermore, current cell-based therapies only target focal lesions, while treatment of large nonisolat...

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Bibliographic Details
Published in:Tissue engineering. Part A 2018-11, Vol.24 (21-22), p.1652-1662
Main Authors: Huang, Brian J., Brown, Wendy E., Keown, Thomas, Hu, Jerry C., Athanasiou, Kyriacos A.
Format: Article
Language:English
Subjects:
Biomechanics
Biomedical engineering
Cartilage
Cell size
Chemical stimuli
Chondrocytes
Collagen
Cytochalasin D
Defects
Joint surgery
Knee
Lysyl oxidase
Mechanical properties
Original
Original Articles
Stem cells
Studies
Tissue engineering
Transforming growth factor-b1
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Summary:Although numerous cartilage engineering methods have been described, few report generation of constructs greater than 4 cm 2 , which is the typical lesion size considered for cell-based therapies. Furthermore, current cell-based therapies only target focal lesions, while treatment of large nonisolated lesions remains an area of great demand. The objective of this study was to scale up fabrication of self-assembled neocartilage from standard sizes of 0.2 cm 2 to greater than 8 cm 2 . Passaged sheep articular chondrocytes were self-assembled into 5 or 25-mm-diameter scaffoldless neocartilage constructs. The 25-mm-diameter constructs grew up to 9.3 cm 2 (areal scale-up of 23) and possessed properties similar to those of the 5-mm-diameter constructs; unfortunately, these large constructs were deformed and are unusable as a potential implant. A novel neocartilage fabrication strategy—employing mechanical confinement, a minute deadweight, and chemical stimulation (cytochalasin D, TGF-β1, chondroitinase-ABC, and lysyl oxidase-like 2 protein)—was found to successfully generate large (25-mm diameter) constructs with flat, homogeneous morphologies. Chemical stimulation increased collagen content and tensile Young's modulus 140% and 240% in the 25-mm-diameter constructs and 30% and 70% in the 5-mm-diameter constructs, respectively. This study not only demonstrated that exceedingly large self-assembled neocartilage can be generated with the appropriate combination of mechanical and chemical stimuli but also that its properties were maintained or even enhanced.
ISSN:1937-3341
1937-335X
DOI:10.1089/ten.tea.2017.0495