Bioprinting is an increasingly important way to create complex biomaterials that direct cell behavior, integrate living cells into bio-inert scaffolding, and even develop genetically programable matrices. The ability to fine-tune the cell microenvironments, however, has been limited.

A new method to bioprint microporous functional living materials using protein-based core-shell microgels appears to overcome those challenges.

Researchers at the University of Cambridge, Nanjing Tech University, and Cambridge University-Nanjing Centre of Technology and Innovation are developing cell-laden microgels to create tunable, microscopic building blocks with the functionalities of macroscopic living materials, according to a pre-print paper.

“The novelty of our work is that this is a bottom-up method to assemble micro-scale building blocks while using top-down extrusion 3D printing to construct robust macroscopic morphologies,” first author Yangteng Ou, a doctoral student at the Tuomas Knowles Lab at the University of Cambridge, tells GEN.

The team packed the aqueous cores of the microgel ink with microfluidically functionalized cells and used extrusion bioprinting to construct microporous protein-based annealed microgel (PAM) scaffolds. Using those scaffolds, scientists can control microporosity and, therefore, the transfer of nutrients and metabolites to the cells.

The microgels are somewhat elastic, making them suitable for bioprinting. Interparticle annealing resulted in PAM scaffolds with enhanced mechanical strength. Degradation times for the PAM scaffolds depends upon the size of the microgel used, with slower degradation associated with smaller microgel sizes. All the scaffolds degraded faster than bulk hydrogel, however. Consequently, the matrices may be engineered and used to control diffusion profiles of molecules in or out of the PAM scaffolds.

Because the scaffolds have varying properties, such as heterogeneously distributed cell populations at the microscale, “significantly enhanced bioactivities were observed in two typical microbial consortia models,” the researchers wrote. They speculate that the reason for the enhanced activities is related to the immobilization and compartmentalization of multi-species microbial communities within the scaffold, which allowed nutrients and metabolites to flow among species efficiently and prevented competitive growth.

The technology is in its early development phase. “The material (gelatin) is not perfectly stable with microbes,” Ou points out.

“We expect this method to be applicable for biofabrication and tissue engineering. That’s what we’ll be working on in the future,” he says. “We hope our work will inspire future works in biofabrication, as a new method for fabricating more complicated and physiologically relevant bio-structures for drug development, or more exciting applications.”