Abstract
To date, the outcomes of cartilage repair have been inconsistent and have frequently yielded mechanically inferior fibrocartilage, thereby increasing the chances of damage recurrence. Implantation of constructs with biochemical composition and mechanical properties comparable to natural cartilage could be advantageous for long-term repair. This study attempted to create such constructs, in vitro, using tissue engineering principles. Bovine synoviocytes were seeded on nonwoven polyethylene terephthalate fiber scaffolds and cultured in chondrogenic medium for 4 weeks, after which uniaxial compressive loading was applied using an in-house bioreactor for 1 h per day, at a frequency of 1 Hz, for a further 84 days. The initial loading conditions, determined from the mechanical properties of the immature constructs after 4 weeks in chondrogenic culture, were strains ranging between 13% and 23%. After 56 days (sustained at 84 days) of loading, the constructs were stained homogenously with Alcian blue and for type-II collagen. Dynamic compressive moduli were comparable to the high end values for native cartilage and proportional to Alcian blue staining intensity. We suggest that these high moduli values were attributable to the bioreactor setup, which caused the loading regime to change as the constructs developed, that is, the applied stress and strain increased with construct thickness and stiffness, providing continued sufficient cell stimulation as further matrix was deposited. Constructs containing cartilage-like matrix with response to load similar to that of native cartilage could produce long-term effective cartilage repair when implanted.
Highlights
Cartilage damage can eventually lead to osteoarthritis, causing pain and reduced joint mobility, seriously compromising the affected individual’s quality of life.[1]
The principles of tissue engineering would be followed in creating such cartilage constructs, where appropriate mechanical stimulation would be applied onto cells seeded onto a suitable 3D scaffold to promote a chondrocyte-like phenotype and matrix
The objectives of this study were, to (1) determine appropriate parameters for mechanical stimulation, namely the range of strains to be applied on the constructs; (2) develop a method for implementing the desired mechanical stimulation; (3) compare the compressive properties of the constructs that were subjected to this mechanical stimulus with those of nonloaded controls and native cartilage; and (4) potentially identify any histological characteristics of the constructs that might be associated with their compressive properties
Summary
Cartilage damage can eventually lead to osteoarthritis, causing pain and reduced joint mobility, seriously compromising the affected individual’s quality of life.[1] It is well recognized that cartilage has a poor capacity for spontaneous self-repair, which is, in part, because of its low cellularity and the lack of vascular and lymphatic systems necessary for efficient healing. It is well documented that biochemical stimulation is a prerequisite for successful differentiation/redifferentiation of cells and desired tissue deposition.[5] Mechanical stimulation is a highly influential factor in the formation of tissue, especially musculoskeletal tissue.[6] In order for mechanical loading to elicit a desired mechanotransductive effect on a cartilage-like construct, the following criteria need to be met:
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