Ultrasound-responsive collagen scaffolds for tissue engineering

Homogeneous nutrient distribution throughout three-dimensional (3-D) scaffolds remains a key challenge in tissue engineering. The buildup of cells on scaffold edges and rapid nutrient uptake along the periphery often cause large regions of the centre to be left unoccupied by cells. Microstreaming associated with acoustic cavitation has been exploited to enhance mass transport in oncological drug delivery and transdermal vaccination, making it an attractive mechanism for promoting nutrient and oxygen distribution in tissue engineering scaffolds. In this work, we seek to use protein cavitation nuclei to synthesize ultrasound-responsive collagen scaffolds. Cavitation nuclei were embedded into the scaffold during fabrication and then exposed to 0.5 MHz focused ultrasound at peak negative pressures ranging from 0.5 to 2.7 MPa to induce inertial cavitation. Acoustic data was collected using passive cavitation detection (PCD) and post processed to isolate harmonics and broadband emissions. We compare the benefits and disadvantages of including cavitation nuclei in the scaffold fabrication process versus adding them to surrounding media during ultrasound exposure, discussing potential use of embedded protein nuclei to induce cell migration and differentiation. Additionally, we examine the effects of cavitation, exposure time, and peak negative pressure on the microstructure of collagen scaffolds, namely, pore size, interconnectivity, and percolation diameter.