Aqueous two-phase system enabled advances for biofabrication

Tissue Engineering is a field aimed at restoring, maintaining, or improving tissue function. While much progress has been made in recent decades, replicating the complexity of tissues, as well as achieving proper vascularization, has not yet been realized. One route that was involved in this progress is the use of 3D (bio)printing to replicate complex and locally defined features. Here, many techniques such as extrusion and light based approaches have been developed, yet still lacking the ability to get close to nature’s complexity.

This thesis introduces the use of aqueous two-phase systems (ATPS) to facilitate the use of particularly extrusion-based printing of low viscous solutions. First, aqueous two-phase enabled low viscosity 3D (LoV3D) bioprinting is introduced, leveraging the stable interface between liquids for printing of solid strands, or hollow perfusable channels and interconnected networks. Via a simple chemical modification, these channels can be functionalized to include cell-guiding moieties or to be mechanically tunable on demand, aiding in achieving higher construct complexity. While hollow channels are interesting for the replication of pre-vascularized tissues for in vivo applications, they can also be utilized for in vitro models. Here, alginate tyramine is introduced as an ATPS forming material that can be easily fabricated and printed into to create channels, that dilate under pressure, aiming to introduce actuation into e.g., Organ-on-Chip systems. To replicate not only larger vessels but also aid in the combination of macro and micro vasculature, the combination with microgel-based baths was explored to connect larger supply vessels to capillary beds.

Overall, this thesis aims at highlighting how the use of aqueous two-phase systems can simplify existing techniques and help introduce complexity in a facile and widely applicable manner.