In the last decade, three-dimensional (3D) printing has allowed the field of complex microfluidic channels to expand rapidly towards channels with variable cross-sections (i.e., beyond simple rounded media with a constant diameter) and channels. Whose trajectory can be outside a single plane and has gained numerous macro- and nanoscale manufacturing advances. Three-dimensional printing is being explored for various biomedical applications and the fabrication of nanomedicines using additive manufacturing techniques. Employing 3D-printed templates for macro-to-micro interfacing, a passively operated microfluidic device was designed. The research seeks to fabricate a biodevice that enables insulin microdosing, creating a subsystem like a microvalve and a microchannel matrix using additive manufacturing techniques. Our systems feature designs that enhance fluid dynamics without affecting the stability of the insulin. We propose using Humalog insulin in tropical climates (up to 30°C) without refrigeration for 28 days. The microvalve has a spiral trajectory with four outlet channels distributed along it. These channels align with the microchannels organized in a 10 mm x 15 mm matrix with 25 microchannels, each with a 770 µm internal diameter. The system delivers a dose of 2,3 mL in 6 minutes. We designed these systems for insulin micro-dosing, but they can also serve similar devices for other drugs.

Recent improvements within the fields of high-throughput screening and 3D tissue culture have provided the possibility of developing in vitro micro-tissue models that can be used to study diseases and screen potential new therapies. This paper reports a proof of concept study on the use of microvalve-based bioprinting to create laminar MSC-chondrocyte co-cultures as an in vitro model of autologous chondrocyte implantation (ACI), an established cellular therapy for osteoarthritis. Microvalve-based bioprinting uses microvalves to deposit cells suspended in a liquid in a consistent and repeatable manner. In this case MSCs and chondrocytes have been sequentially deposited into an insert based transwell system in order to create a laminar co-culture, with variations in the ratios of the cell types used to investigate the potential for MSCs to stimulate improved repair. Histological and indirect immunofluorescence staining revealed the formation of dense tissue structures within the chondrocyte and MSC-chondrocyte cell co-cultures, alongside the establishment of a proliferative region at the base of the tissue. No stimulatory or inhibitory effect in terms of ECM production was observed through the introduction of MSCs, although the potential for an immunomodulatory benefit remains. This proof-of-concept study therefore provides a novel method to enable the scalable production of therapeutically relevant micro-tissue models that can be used for in vitro research to optimise ACI procedures.