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Flink Fast! Here’s a Biodesign Paper for Happy ID Holidays

We’ve often reported about the biomimetics revolution, in which human engineers try to imitate biological designs. In a sense, biomimicry is a form of plagiarism, like copying another student’s science project. Here is another revolution that’s less like plagiarism and more like partnership. Why imitate bacteria when we can join forces with them?

3D printing has already opened up fantastic new ways of designing things using information to control the arrangement of building blocks. Just supply the materials and the design, and the printer can construct almost any shape. Often the materials are resins or metal powders, but almost any substance could work. That gave researchers in Zurich and Dublin an idea: Why not print with bacteria? Their open-access paper in Science Advances announces a new design revolution: “3D printing of bacteria into functional complex materials.”

Despite recent advances to control the spatial composition and dynamic functionalities of bacteria embedded in materials, bacterial localization into complex three-dimensional (3D) geometries remains a major challenge. We demonstrate a 3D printing approach to create bacteria-derived functional materials by combining the natural diverse metabolism of bacteria with the shape design freedom of additive manufacturing. To achieve this, we embedded bacteria in a biocompatible and functionalized 3D printing ink and printed two types of “living materials” capable of degrading pollutants and of producing medically relevant bacterial cellulose. With this versatile bacteria-printing platform, complex materials displaying spatially specific compositions, geometry, and properties not accessed by standard technologies can be assembled from bottom up for new biotechnological and biomedical applications. [Emphasis added.]

As long as you provide living space in a “biocompatible medium,” the bacteria are perfectly happy to generate cellulose or degrade pollutants within their little condos, and engineers can build the condos in any shape they want. The possibilities are endless:

Bacteria are able to thrive in virtually any ecological niche because of their adaptive and diverse metabolic activity. Owing to such a metabolic diversity, richer than in any other types of organisms, bacteria create, for example, physical matter in the form of biofilms that warrant survival even in hostile environments. Biofilms adapt their mechanical properties under stress to match conditions imposed by the surrounding environment with a great diversity of biopolymer. During growth in biofilms, bacteria can also form and degrade a plethora of compounds, which are often used to synthesize chemicals, biopolymers, enzymes, and proteins relevant for the food, medical, and chemical industries. Moreover, bacteria are able to form calcium carbonate, magnetites, and biopolymers, which could lead to a new generation of biomineralized composites, biodegradable plastics, and functional materials for biomedical applications. This provides these microorganisms with a wide spectrum of functional properties that hold potential for a variety of novel applications.

Think, for instance, how this could help solve the problem of plastic in the oceans. Put plastic-degrading bacteria into floating, biodegradable platforms and turn them loose in the North Pacific Gyre. Or print collagen-making bacteria into a scaffold to repair bones or tendons. Who knows what lies ahead? This team had better be filing patents!

In particular, bacterial cellulose has been found to be extremely useful in the medical industry because of its cell biocompatibility, making it ideal for tissue engineering. So far, bacterial cellulose has been manufactured in situ in the form of surface-patterned implants, ear transplants, and potential blood vessels by diffusing oxygen through nanopatterned and 3D-shaped silicone molds. In these examples, biofilms have been mainly formed in a nonimmobilized state at a variety of surfaces and interfaces by depositing a layer of bacteria initially suspended in a fluid culture medium on the desired substrate. Immobilizing bacteria in a viscoelastic matrix that could be free-formed into intricate geometries and combined with different microorganisms to achieve spatial cellular and chemical composition control would enable the fabrication of materials with thus far inaccessible dynamic functionalities.

Here is a double-design story. Humans design the scaffolds, and bacteria design the goods. Our information coded in computer programs designs the molds, and their information coded in DNA designs the functional enzymes or proteins.

Earlier attempts at creating biological structures required injecting bacteria into molds after the fact. These engineers found a way to print the structure in one step with “functional living ink” — which they dub “Flink.”

Here, we report on a 3D printing platform that enables the digital fabrication of free-standing cell-laden hydrogels with full control over the spatial distribution and concentration of cells or microbes in complex and self-supporting 3D architectures. To this end, we develop and study a functional living ink, called “Flink,” that is a biocompatible immobilization medium that exhibits the viscoelastic properties required for 3D printing of various cells through multimaterial direct ink writing (DIW). The freedom of shape and material composition provided by this printing technique is combined with the metabolic response of microorganisms to enable the digital fabrication of bacteria-derived living materials featuring unprecedented functionalities, such as adaptive behavior, pollutant degradation, and structure formation in the form of cellulose reinforcement. As a novel additive manufacturing approach, Flink 3D printing opens the possibility to combine different organisms and chemistries in a single process, allowing for the digital shaping of living materials into new geometries and adaptive functional architectures.

The heroes of the story are the bacteria. Programming the mold is the easy part. Designing an enzyme or a protein from scratch would require arranging hundreds or thousands of DNA letters, transcribing them into RNA strands, and using molecular factories called ribosomes to translate them into proteins that will fold properly (sometimes with help from chaperone machines). It’s easier to let the bacteria do that. The humans controlling the printer are glorified chicken ranchers who build the chicken coops and let the birds do the hard part — laying eggs. But oh, the possibilities! Will medics on the field re-grow skin on burn victims by applying Flink bandages? Will Flink bobbers clean up oil spills? Think Flink!

Two examples of living materials are presented here to demonstrate the possible functionalities arising from the metabolic activity and growth of bacteria embedded within 3D-printed structures. As a first example, the phenol degradation capability of Pseudomonas putida immobilized in a 3D-printed lattice is demonstrated for bioremediation applications. A second example shows the growth of A. xylinum in a complex-shaped 3D-printed architecture that enables the in situ formation of bacterial cellulose relevant for biomedical applications.

Most of the paper deals with the practical problems the team had to solve to get Flink to work. In the conclusion, they show why every hospital (or plastic surgery clinic) is going to want its own Flink printer:

Given the emerging importance of bacterial cellulose as skin replacements and as tissue envelops in organ transplantation the possibility to form bacterial cellulose in any desired 3D shape allows us to apply the decellularized cellulose onto the site of interest without risking the detachment of the skin graft upon movement. The in situ formation of reinforcing cellulose fibers within the hydrogel is particularly attractive for regions under mechanical tension, such as the elbow and knee, or when administered as a pouch onto organs to prevent fibrosis after surgical implants and transplantations. Cellulose films grown in complex geometries precisely match the topography of the site of interest, preventing the formation of wrinkles and entrapments of contaminants that could impair the healing process. We envision that long-term medical applications will benefit from the presented multimaterial 3D printing process by locally deploying bacteria where needed.

We won’t get into worries about uses in biological warfare at this time; that’s a moral issue best addressed by our bioethicist colleague Wesley J. Smith or by defense strategists. But for entrepreneurs with beneficial motives, the future looks bright for this design partnership that will use living materials to make the world a better place.