Four-Dimensional Bioprinting: Harnessing Active Mechanics to Build with Living Inks.

Three-dimensional (3D) printing can be beneficial to tissue engineers and the regenerative medicine community because of its potential to rapidly build elaborate 3D structures from cellular and material inks. However, predicting changes to the structure and pattern of printed tissues arising from the mechanical activity of constituent cells is technically and conceptually challenging. This perspective is targeted to scientists and engineers interested in 3D bioprinting, but from the point of view of cells and tissues as mechanically active living materials.

Transcriptional regulation of living materials via extracellular electron transfer.

Engineered living materials combine the advantages of biological and synthetic systems by leveraging genetic and metabolic programming to control material-wide properties. Here, we demonstrate that extracellular electron transfer (EET), a microbial respiration process, can serve as a tunable bridge between live cell metabolism and synthetic material properties. In this system, EET flux from Shewanella oneidensis to a copper catalyst controls hydrogel cross-linking via two distinct chemistries to form living synthetic polymer networks.

A hybrid transistor with transcriptionally controlled computation and plasticity.

Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium Shewanella oneidensis that enable the transduction of biological computations to electrical responses.

MAGIC matrices: freeform bioprinting materials to support complex and reproducible organoid morphogenesis.

Organoids are powerful models of tissue physiology, yet their applications remain limited due to their relatively simple morphology and high organoid-to-organoid structural variability. To address these limitations we developed a soft, composite yield-stress extracellular matrix that supports optimal organoid morphogenesis following freeform 3D bioprinting of cell slurries at tissue-like densities. The material is designed with two temperature regimes: at 4 °C it exhibits reversible yield-stress behavior to support long printing times without compromising cell viability.

A Hybrid Transistor with Transcriptionally Controlled Computation and Plasticity.

Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium that enable the transduction of biological computations to electrical responses.

Programming the Self-Organization of Endothelial Cells into Perfusable Microvasculature.

The construction of three-dimensional (3D) microvascular networks with defined structures remains challenging. Emerging bioprinting strategies provide a means of patterning endothelial cells (ECs) into the geometry of 3D microvascular networks, but the microenvironmental cues necessary to promote their self-organization into cohesive and perfusable microvessels are not well known. To this end, we reconstituted microvessel formation by patterning thin lines of closely packed ECs fully embedded within a 3D extracellular matrix (ECM) and observed how different microenvironmental parameters influenced EC behaviors and their self-organization into microvessels.

Extracellular Electron Transfer Enables Cellular Control of Cu(I)-Catalyzed Alkyne-Azide Cycloaddition.

Extracellular electron transfer (EET) is an anaerobic respiration process that couples carbon oxidation to the reduction of metal species. In the presence of a suitable metal catalyst, EET allows for cellular metabolism to control a variety of synthetic transformations. Here, we report the use of EET from the electroactive bacterium for metabolic and genetic control over Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC).

Genetic Control of Radical Cross-linking in a Semisynthetic Hydrogel.

Enhancing materials with the qualities of living systems, including sensing, computation, and adaptation, is an important challenge in designing next-generation technologies. Living materials address this challenge by incorporating live cells as actuating components that control material function. For abiotic materials, this requires new methods that couple genetic and metabolic processes to material properties.

Extracellular Electron Transfer by Shewanella oneidensis Controls Palladium Nanoparticle Phenotype.

The relative scarcity of well-defined genetic and metabolic linkages to material properties impedes biological production of inorganic materials. The physiology of electroactive bacteria is intimately tied to inorganic transformations, which makes genetically tractable and well-studied electrogens, such as Shewanella oneidensis, attractive hosts for material synthesis. Notably, this species is capable of reducing a variety of transition-metal ions into functional nanoparticles, but exact mechanisms of nanoparticle biosynthesis remain ill-defined.

as a living electrode for controlled radical polymerization.

Metabolic engineering has facilitated the production of pharmaceuticals, fuels, and soft materials but is generally limited to optimizing well-defined metabolic pathways. We hypothesized that the reaction space available to metabolic engineering could be expanded by coupling extracellular electron transfer to the performance of an exogenous redox-active metal catalyst. Here we demonstrate that the electroactive bacterium can control the activity of a copper catalyst in atom-transfer radical polymerization (ATRP) via extracellular electron transfer.

High-titer antibody depletion enhances discovery of diverse serum antibody specificities.

The human antibody repertoire is a unique repository of information regarding infection, inflammation, and autoimmunity of the past, present, and future. However, antibodies can span vast ranges of concentrations with varying affinities and the repertoire is often heavily polarized by a few species. These complexities lead to difficulties detecting and characterizing low abundance antibody species that may be relevant to disease.