Modulation of the mechanical properties of tissue engineered cartilage.
Cartilaginous constructs have been grown in vitro using chondrocytes, biodegradable polymer scaffolds, and tissue culture bioreactors. In the present work, we studied how the composition and mechanical properties of engineered cartilage can be modulated by the conditions and duration of in vitro cultivation, using three different environments: static flasks, mixed flasks, and rotating vessels. After 4-6 weeks, static culture yielded small and fragile constructs, while turbulent flow in mixed flasks induced the formation of an outer fibrous capsule; both environments resulted in constructs with poor mechanical properties. The constructs that were cultured freely suspended in a dynamic laminar flow field in rotating vessels had the highest fractions of glycosaminoglycans and collagen (respectively 75% and 39% of levels measured in native cartilage), and the best mechanical properties (equilibrium modulus, hydraulic permeability, dynamic stiffness, and streaming potential were all about 20% of values measured in native cartilage). Chondrocytes in cartilaginous constructs remained metabolically active and phenotypically stable over prolonged cultivation in rotating bioreactors. The wet weight fraction of glycosaminoglycans and equilibrium modulus of 7 month constructs reached or exceeded the corresponding values measured from freshly explanted native cartilage. Taken together, these findings suggest that functional equivalents of native cartilage can be engineered by optimizing the hydrodynamic conditions in tissue culture bioreactors and the duration of tissue cultivation.
Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, USA.
I
I
Martin
B
B
Obradovic
S
S
Treppo
A J
AJ
Grodzinsky
R
R
Langer
L E
LE
Freed
G
G
Vunjak-Novakovic
D000818:Animals; D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D001698:Biomedical Engineering / Q000379:methods*; D019149:Bioreactors; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism; D002417:Cattle; D018929:Cell Culture Techniques; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D012212:Rheology; D013997:Time Factors
D001672:Biocompatible Materials; D006025:Glycosaminoglycans; D003094:Collagen