High-throughput ultrasound-based volumetric 3D printing for tissue engineering

Cardiovascular diseases are the leading cause of death globally. Efficient drug testing and disease models are needed to reduce their death toll. Myocardial cell constructs, e.g. spheroids, organoids, or organs on a chip, hold promise as disease models and can reduce animal testing. Unfortunately, cell constructs often lack the natural spatial complexity of their in-vivo counterparts, and consequently the cells remain immature and non-differentiated. Although, 3D printing offers great flexibility regarding the printed structure some limitations apply: the printing process is either slow, or not suited for printing the small-scale nested structures needed to create viable and functional myocardial cell constructs. To 3D bio print viable myocardial cell constructs, we must therefore break through several roadblocks limiting the potential of bioprinting. Our solution, coined SONOCRAFT, combines rapid volumetric 3D printing technology with ultrasonic particle manipulation to create centimetre-long aligned cardiac constructs within hydrogels. An artificial vasculature, incorporated within the hydrogel matrix, assures perfusion with oxygen and nutrients. Acoustic particle manipulation our tool of choice for cell manipulation as it is cheap, biocompatible, label-free and achieves the required resolution. To reach the objectives SonoPrint is equipped with a range of advanced features: (i) an acoustophoresis chamber for precise cell patterning in 3D; (ii) microfluidic nozzles for injecting multiple cell types; (iii) moveable printheads for flexible cell deposition; (iv) a temperature-controlled cell culture incubator; and (v) full automation for user-friendly operation. The visionary SONOCRAFT holds potential to transform tissue engineering, regenerative medicine, drug screening, and disease modelling with its technological breakthroughs overcoming current limitations in the field.