Liquid-embedded (bio)printing of alginate-free, standalone, ultrafine, and ultrathin-walled cannular structures

Abstract

While there has been considerable success in the three-dimensional bioprinting of relatively large standalone filamentous tissues, the fabrication of solid fibers with ultrafine diameters or those cannular featuring ultrathin walls remains a particular challenge. Here, an enabling strategy for (bio)printing of solid and hollow fibers whose size ranges could be facilely adjusted across a broad spectrum, is reported, using an aqueous two-phase embedded (bio)printing approach combined with specially designed cross-linking and extrusion methods. The generation of standalone, alginate-free aqueous architectures using this aqueous two-phase strategy allowed freeform patterning of aqueous bioinks, such as those composed of gelatin methacryloyl, within the immiscible aqueous support bath of poly(ethylene oxide). Our (bio)printing strategy revealed the fabrication of standalone solid or cannular structures with diameters as small as approximately 3 or 40 μ m, respectively, and wall thicknesses of hollow conduits down to as thin as <5 μ m. With cellular functions also demonstrated, we anticipate the methodology to serve as a platform that may satisfy the needs for the different types of potential biomedical and other applications in the future, especially those pertaining to cannular tissues of ultrasmall diameters and ultrathin walls used toward regenerative medicine and tissue model engineering.

Dissecting the Interplay Mechanism among Process Parameters toward the Biofabrication of High‐Quality Shapes in Embedded Bioprinting

“…[32,38] During high-speed bioprinting, bubbles may be introduced into the support bath along the printing path, which affects the bioprinting process and constrains the printing speed. [96] Since the nozzle moves through the support bath, a welldefined fiber morphology could be obtained by balancing printing speed and rheological properties. A comprehensive list of parameters (i.e., printing speed, nozzle size, etc.)…”

Organ bioprinting: progress, challenges and outlook

“…Currently, embedded bioprinting has become one of the mainstream techniques to fabricate vascular tissues/organs. In a recent study, Tang et al 119 generated a freestanding and alginatefree cannula tissue with an ultra-fine lumen (3-40 mm) and ultra-thin walls (5 mm) using an embedded bioprinting process, in which the polyethylene oxide (PEO) was employed as the support bath and GelMA as the aqueous bioink. To reproduce both the external geometry and internal vascular structure of an organ simultaneously, Fang et al 120 developed a technique termed sequential printing in reversible ink templates (SPIRIT), where the biphasic bioink of GelMA (i.e., microgel phase and hydrogel phase) served as both a bioink and a support bath to enable the embedded bioprinting.…”

“…In a recent study, Tang et al . 119 generated a freestanding and alginate-free cannula tissue with an ultra-fine lumen (3–40 μm) and ultra-thin walls (5 μm) using an embedded bioprinting process, in which the polyethylene oxide (PEO) was employed as the support bath and GelMA as the aqueous bioink. To reproduce both the external geometry and internal vascular structure of an organ simultaneously, Fang et al .…”

Versatile xanthan gum-based support bath material compatible with multiple crosslinking mechanisms: rheological properties, printability, and cytocompatibility study

“…While some polymeric solution [10] and hydrogel systems have been developed as support baths for extrusion-based bioprinting with their respective advantages and drawbacks as summarized in table 1, there are several outstanding challenges and technical gaps remaining. First, the preparation of hydrogel support materials can be time-consuming and technically complicated.…”