New “bio-ink” brings science fiction into reality

  When it comes to printing, just like printing in our common sense, 3D printing also needs “ink”. In fact, the role of “ink” in 3D printing is crucial. In the past, 3D printing inks were mainly plastic or powder materials. With the gradual increase in the application fields of 3D printing, there are various types of 3D printing “inks”, the most striking of which is the “bio-ink”
  Harvard Medical School . Professor Y. Shrike Zhang’s research group has published many influential achievements in the field of 3D printing. Professor Zhang’s research areas include bioprinting and the construction and application of organ-on-a-chip platforms. He has published more than 260 research papers and reviews in related fields. Including journals such as PNAS, Science, Nat.Rev.Mater., Nat.Rev.MethodsPrimers, Nat.Rev.Nephrol., Matter, Nat.Commun., Nat.Protoc., AdvMater, etc. published as the first or corresponding author, among which More than 45 cover articles; research results have been reported by BBC, FoxNews, TheBostonGlobe/STATNews and other media.

  Professor Zhang was listed by Stanford University as one of the top 2% scientists in the world, and was selected as a Clarivate Analytics Highly Cited Scientist. The IEEE Optoelectronics Society Young Investigator Award is established to recognize young researchers (under the age of 35) who have made outstanding technical contributions to optoelectronics (broadly defined). At the same time, Professor Zhang serves as the editor-in-chief, associate editor or editorial board of more than 20 journals, and has won more than 40 international and regional awards.
  Recently, Professor Y. Shrike Zhang and his collaborating team published a new type of bioink in Nature Communications, which is expected to achieve self-healing of materials. In traditional bio-ink, bacteria or other microbial cells are usually added to the ink, that is, biology is only one of the ingredients of the ink’s formulation. The new bioink jointly developed by Professor Zhang and his collaborating team creatively utilizes genetic engineering, that is, by genetically engineering E. Together, and after some proper processes, a new type of bio-ink was finally invented. In this bio-ink, bacteria are not only used as components of the ink, but also directly secrete and manufacture the ink itself. Based on this principle, the biological material printed by this ink can theoretically secrete new fibers through corresponding chemical stimulation. for self-repair.
  This work was completed by the team of Professor Zhang and Associate Professor Neil Joshi of the Institute of Life Systems at Northeastern University. Among them, Josh’s team was responsible for transforming E. coli to obtain engineering bacteria that can make bioinks. Professor Zhang’s team assisted in the printing work. Finally, through the cooperation of the two teams, they obtained this new type of bioink and verified its printability. and functionality.
  Bioinks need to have adjustable mechanical strength, high cell viability and better printing clarity. The team imagined that, instead of embedding microorganisms in a bioink that mimics the extramatrix, could it be possible to use the extramatrix of the microorganism itself to form a bioink?
  In nature, the outer matrix of microorganisms can still achieve interfacial adhesion and maintain its necessary growth in harsh environments, and a CsgA nanofiber plays a key role in it. CsgA nanofibers are formed by self-assembly of CsgA monomer protein, which is rich in β-sheet structure, which can make the nanofiber structure regular, and the regular structure can provide the material with better environmental tolerance, such as high and low temperature resistance It is stable in acid-base solution and has good friction and wear performance.

  However, the ink composed of CsgA nanofibers alone is not viscous enough. Inspired by the coagulation cascade, the team thought of the α short chain structure at the N-terminus of fibrin and the γ short chain structure at the C-terminus of fibrin. One of the two short chains is like a ball-shaped handle and the other is like a hole, and the two protein domains can be twisted together to form a structure similar to a bracelet.
  Then, based on the assumption, the Josh team used genetic engineering to functionalize the CsgA monomer protein, and connected the α short chain and the γ short chain to the N-terminus and C-terminus of the CsgA monomer protein, respectively. While maintaining its own function, it does not affect the ability of CsgA protein itself to self-assemble to form nanofibers, but it introduces non-covalent crosslinks between nanofibers to enhance mechanical stability and maintain shear-thinning properties. Finally, after some processes, this new type of bio-ink is made.
  The genetic engineering mentioned in this article is generally used in the field of biology. In short, it uses some tool enzymes to splicing and recombining genes, so that foreign genes can be stably inherited and express the traits that humans want according to human wishes. We can understand genes with different functions as different modules, and combine different modules according to our needs to obtain the desired biological function.
  Using the idea of ​​genetic engineering, the team then installed growth regulation modules and modules that secrete special substances on the genes of bacteria. When stimulated by corresponding chemical substances, these modules begin to perform their functions, and the bacteria show corresponding biological functions. reaction.
  The team printed two sets of 3D structures with living components with the new bioink, and then successfully induced the 3D structures to produce an active material that can sequester toxic substances through chemical induction, and the other set of 3D structures was successfully secreted under chemical induction. anticancer substances.

  Referring to the application prospects of this new type of bio-ink, Professor Zhang is very excited. He and his team hope that in the future, the 3D structures printed by this new type of ink can help people to achieve self-healing of building materials or other previously impossible in harsh environments. Implemented active function.
  A very important feature of this paper is that it uses the programmable principle of microbial genes to rationally control the mechanical properties of bioinks, and at the same time endows 3D printed structures with many tunable biological functions.
  The results of this paper also bring more possibilities to the field of living materials. Imagine that in the future, we will create a “golden bell” tailored for cancer tissues, this golden bell will continuously secrete anti-cancer substances, so that cancer cells have nowhere to spread; or in the future we will live in 3D printed houses, When the house is damaged, there is no need to add another brick and tile, the building material itself can be perfectly “self-healing”, and even the kitchen material can have a special functional area for secreting milk protein.