Search

Geometric and structural integrity often deteriorate in 3D printed cell-laden constructs over time due to cellular compaction and hydrogel shrinkage. This study introduces a new approach that synergizes the advantages of cell compatibility of biological hydrogels and mechanical stability of elastomeric polymers for structure fidelity maintenance upon stereolithography and extrusion 3D printing. Enabling this advance is the composite bioink, formulated by integrating elastomeric microparticles from poly(octamethylene maleate (anhydride) citrate) (POMaC) into biologically derived hydrogels (fibrin, gelatin methacryloyl (GelMA), and alginate). The composite bioink enhanced the elasticity and plasticity of the 3D printed constructs, effectively mitigating tissue compaction and swelling. It exhibited a low shear modulus and a rapid crosslinking time, along with a high ultimate compressive strength and resistance to deformation from cellular forces and physical handling; this was attributed to packing and stress dissipation of elastomeric particles, which was confirmed via mathematical modelling. Enhanced functional assembly and stability of human iPSC-derived cardiac tissues and primary vasculature proved the utility of the composite bioink in tissue engineering. In vivo implantation studies revealed that constructs containing POMaC particles exhibited improved resilience against host tissue stress, enhanced angiogenesis, and infiltration of pro-reparative macrophages.

The heterogeneity of diseased tissue causes major challenges in the detection and treatment of disease. Such challenges have motivated the development of tools for single-cell isolation and analysis. However, many cell isolation methods in microfluidics rely on the use of cell-labeling steps or expose cells to potentially harmful forces. Here, we present a microfluidic method for label-free control of cell-encapsulating biocompatible droplets using negative magnetophoresis. Our system is distinguished from previous microfluidic diamagnetic sorting approaches by the encapsulation of the cells inside droplets, which isolates the cells from the magnetic continuous phase. The droplet phase is comprised of cells suspended in their growth culture medium, and all of the magnetic content is contained in the oil-based continuous phase. At a flow-focusing junction, empty droplets and cell-encapsulating droplets are both generated and surrounded by the magnetic continuous phase. Cell encapsulation produces a size distinction between empty droplets and cell-encapsulated droplets. Through the application of a permanent magnet to the system, diamagnetic size-based sorting of empty droplets from cell-encapsulated droplets is achieved with a purity of ∼84% in a single pass. Additionally, since the encapsulated cells are completely isolated from the magnetic content in the continuous phase, 88% cell-viability is observed after a two-hour incubation period. If combined with a single-cell assay, this system can provide label-free isolation of viable cells at a high purity for subsequent downstream analysis.