Bioengineering neocartilage grafts of human articular chondrocytes in a custom-built microfluidic perfusion bioreactor with integrated ultrasound standing wave trap.
For over a decade, advancements in ultrasound-enhanced drug delivery strategies have 3 demonstrated remarkable success in providing targeted drug delivery for a broad range of diseases.
4In order to achieve enhanced drug delivery, these strategies harness the mechanical effects from 5 bubble oscillations (i.e., cavitation) of a variety of exogenous cavitation agents. Recently, solid 6 cavitation agents have emerged due to their capacity for drug-loading and sustained cavitation 7 duration. Unlike other cavitation agents, solid cavitation agents stabilize gaseous bubbles on 8 hydrophobic surface cavities. Thus, the design of these particles are crucial. In this review, we 9 provide an overview of the different designs for solid cavitation agents such as nanocups, 10 nanocones, and porous structures as well as the current status of their development. Considering 11 the numerous advantages of solid cavitation agents, we anticipate further innovations for this new 12 type of cavitation agent across a broad range of biomedical applications.
Bioacoustofluidics can be used to trap and levitate cells within a fluid channel, thereby facilitating scaffold-free tissue engineering in a 3D environment. In the present study, we have designed and characterised an acoustofluidic bioreactor platform, which applies acoustic forces to mechanically stimulate aggregates of human articular chondrocytes in long-term levitated culture. By varying the acoustic parameters (amplitude, frequency sweep, and sweep repetition rate), cells were stimulated by oscillatory fluid shear stresses, which were dynamically modulated at different sweep repetition rates (1-50 Hz). Furthermore, in combination with appropriate biochemical cues, the acoustic stimulation was tuned to engineer human cartilage constructs with structural and mechanical properties comparable to those of native human cartilage, as assessed by immunohistology and nano-indentation, respectively. The findings of this study demonstrate the capability of acoustofluidics to provide a tuneable biomechanical force for the culture and development of hyaline-like human cartilage constructs in vitro.
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