Sonochemical Degradation of Gelatin Methacryloyl to Control Viscoelasticity for Inkjet Bioprinting.

Inkjet printing enables the mimicry of the microenvironment of natural complex tissues by patterning cells and hydrogels at a high resolution. However, the polymer content of an inkjet-printable bioink is limited as it leads to strong viscoelasticity in the inkjet nozzle. Here it is demonstrated that sonochemical treatment controls the viscoelasticity of a gelatin methacryloyl (GelMA) based bioink by shortening the length of polymer chains without causing chemical destruction of the methacryloyl groups. The rheological properties of treated GelMA inks are evaluated by a piezo-axial vibrator over a wide range of frequencies between 10 and 10 000 Hz. This approach enables to effectively increase the maximum printable polymer concentration from 3% to 10%. Then it is studied how the sonochemical treatment effectively controls the microstructure and mechanical properties of GelMA hydrogel constructs after crosslinking while maintaining its fluid properties within the printable range. The control of mechanical properties of GelMA hydrogels can lead fibroblasts more spreading on the hydrogels. A 3D cell-laden multilayered hydrogel constructs containing layers with different physical properties is fabrictated by using high-resolution inkjet printing. The sonochemical treatment delivers a new path to inkjet bioprinting to build microarchitectures with various physical properties by expanding the range of applicable bioinks.

High-Frequency Rheological and Piezo-Voltage Waveform Characterization of Inkjet-Printed Polymer-Based Dopant-Source Inks.

This work focuses on developing an understanding of the rheological properties of polymer-based dopant-source inks at the timescales relevant to inkjet printing and their corresponding roles in determining the production of defect-free droplets. Ink-specific optimization of printing processes for phosphorus and boron dopant-source inks with different compositions is demonstrated. Rheological flow curves measured by a piezo axial vibrator (PAV) were used to study the changes in complex viscosity (η*) and in the elastic (G') and viscous (G″) components of the shear modulus (G*) with respect to changes in frequency (from fmin = 1 kHz to fmax = 10 kHz) to obtain an insight into the high-frequency behaviour of inks, as well as the effects of temperature (25 °C and 45 °C) and the natural aging time of the inks. Inks demonstrating complex viscosity η*min ≥ 2 mPas to η*max ≤ 20 mPas and an elastic modulus G' ≤ 20 Pa, produced droplets with negligible defects. Of the three rheological parameters (η*, G' and G″), the elastic component (G') of the shear modulus was observed to have the greatest significance in determining the stability and homogeneity of ink droplets, thus dictating the quality of the printed structures. The reliability and stability of droplet formation were further investigated through voltage waveform simulation using an oscilloscope.

2D and 3D inkjet printing of biopharmaceuticals - A review of trends and future perspectives in research and manufacturing.

There is an ongoing global shift in pharmaceutical business models from small molecule drugs to biologics. This increase in complexity is in response to advancements in our diagnoses and understanding of diseases. With the more targeted approach coupled with its inherently more costly development and manufacturing, 2D and 3D printing are being explored as suitable techniques to deliver more personalised and affordable routes to drug discovery and manufacturing. In this review, we explore first the business context underlying this shift to biopharmaceuticals and provide an update on the latest work exploring discovery and pharmaceutics. We then draw on multiple disciplines to help reveal the shared challenges facing researchers and firms aiming to develop biopharmaceuticals, specifically when using the most commonly explored manufacturing routes of drop-on-demand inkjet printing and pneumatic extrusion. This includes separating out how to consider mechanical and chemical influences during manufacturing, the role of the chosen hardware and the challenges of aqueous formulation based on similar challenges being faced by the printing industry. Together, this provides a review of existing work and guidance for researchers and industry to help with the de-risking and rapid development of future biopharmaceutical products.