Tunable and Compartmentalized Multimaterial Bioprinting for Complex Living Tissue Constructs

Abstract

Recapitulating inherent heterogeneity and complex microarchitectures within confined print volumes for developing implantable constructs that could maintain their structure in vivo has remained challenging. Here, we present a combinational multimaterial and embedded bioprinting approach to fabricate complex tissue constructs that can be implanted postprinting and retain their three-dimensional (3D) shape in vivo. The microfluidics-based single nozzle printhead with computer-controlled pneumatic pressure valves enables laminar flow-based voxelation of up to seven individual bioinks with rapid switching between various bioinks that can solve alignment issues generated during switching multiple nozzles. To improve the spatial organization of various bioinks, printing fidelity with the z-direction, and printing speed, self-healing and biodegradable colloidal gels as support baths are introduced to build complex geometries. Furthermore, the colloidal gels provide suitable microenvironments like native extracellular matrices (ECMs) for achieving cell growths and fast host cell invasion via interconnected microporous networks in vitro and in vivo. Multicompartment microfibers (i.e., solid, core−shell, or donut shape), composed of two different bioink fractions with various lengths or their intravolume space filled by two, four, and six bioink fractions, are successfully printed in the ECM-like support bath. We also print various acellular complex geometries such as pyramids, spirals, and perfusable branched/linear vessels. Successful fabrication of vascularized liver and skeletal muscle tissue constructs show albumin secretion and bundled muscle mimic fibers, respectively. The interconnected microporous networks of colloidal gels result in maintaining printed complex geometries while enabling rapid cell infiltration, in vivo.

Review on Porous Scaffolds Generation Process: A Tissue Engineering Approach

“…Multimaterial nozzles can control the flow of different bioinks through different paths or deposition rates, 133 as in Figure 6e. This is also known as parallel printing, advantaging the coaxial nozzle in the sense of using more than two materials.…”

“…(e) Multimaterial head for extrusion of up to six different materials. Reproduced from ref . Copyright 2022 American Chemical Society.…”

A dive into the bath: embedded 3D bioprinting of freeform in vitro models

“…68 Moreover, ECM-like colloidal gel-based support bath offered a microenvironment to enhance the spatial organization of bioinks, printing fidelity and speed to build complex constructs. 68 Current fabrication strategies of organ-mimetic constructs for therapeutic applications have shown limited success due to the challenges in the recapitulation of human scale, complex microarchitectures with densely packed, multiple cell types of functional native tissues. 69,70 Considering that the main aim of bioengineered in vitro models is to recreate key functional hallmarks of human tissues and organs, the same limitations apply to these systems.…”

“…Organoids have been recently proposed as building blocks for the production of physiologically relevant constructs, 43,62,68,69 as they show unique self-organization potential and specific tissue mimetic features. 70 For instance, sacrificial bioprinting in a support matrix made of organ building blocks (OBBs) produced from induced pluripotent stem cell derived (iPSC) organoids, creates scalable, perfusable tissue mimetic constructs with vascular networks.…”

Multimaterial Hydrogel 3D Printing

“…Hassan et al performed coaxial extrusion printing in a colloidal gel support bath, allowing for the preparation of delicate multimaterial tissue structures. [148] Up to seven bioinks could be printed during a single job, with the option of individual or side-by-side extrusion. The degradable support gel was shown to facilitate fast cell growth and host cell invasion upon implantation.…”