Numerical Simulation of a Novel Laser-Assisted Method Enabling Multiscale Bio-Printing

Three-dimensional (3D) bio-printing has emerged as one of the most influential applications of printing technologies, aiming to address the increased demand for living constructs with long term mechanical and biological stability suitable for transplantation and drug screening applications [1]. Currently, an open challenge in the laser bioprinting field is the fabrication of living constructs of biologically relevant size (~cm3) with micrometric resolution, i.e., multiscale printing. The paper proposes a novel laser-assisted method that enables multiscale printing of 3D constructs. The method is inspired by studies in the field of laser-assisted drug injection [2]. We will discuss the bio-printing principle, involving a sequence of mechanisms (Figure 1): i) nanosecond (ns) pulsed laser (τ = 6 ns, λ = 532 nm) interaction with liquid, ii) cavitation, iii) bubble dynamics, iv) fluid structure interaction, and v) jet dynamics. We used a multiphysics simulation software (COMSOL) to numerically simulate the involved mechanisms. To calculate laser-induced bubble dynamics in a closed chamber, we solved the Rayleigh-Plesset differential equation coupled to a modified Tait equation of state, which accounts for the pressure increase in the chamber because of the laser-induced bubble expansion. We considered 20% conversion of the laser pulse energy to bubble energy, which is a value well documented in the literature [3]. We applied the calculated spatiotemporal dynamics of the bubble boundary as a moving wall to calculate fluid-membrane interaction and the resulting membrane velocity. The membrane velocity profile was then applied to a two-phase flow model to simulate the bio-ink ejection dynamics. We will present the dependence of the jet-dynamics on various key experimental conditions, including liquid rheological properties (dynamic viscosity: 0.89-26.85 mPa·s, density: 996.89-1190.4 kg/m3, laser energy: 5-500J). Finally, we will present an optimization study aiming to reproducible and controllable printing of bio-ink drops with the following characteristics: ejection velocity 5-50 m/s, volume 0.05-30 nL, at the kHz repetition rate regime. Our results demonstrate reliable high-resolution bio-printing for an extended bio-ink viscosity range, representing a model bio-ink that is currently impossible to print using a single conventional bio-printing technology.

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