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Cells construct living composite polymers for biomedical functions: Initial demonstration builds drug delivery system that protects the gut microbiome from antibiotics

Biomedical engineers at Duke University have demonstrated that a category of interwoven composite supplies referred to as semi-interpenetrating polymer networks (sIPNs) might be produced by living cells. The strategy may make these versatile supplies extra biologically appropriate for biomedical functions corresponding to time-delayed drug delivery programs.

The analysis seems on-line on June 8 in the journal Nature Communications.

The idea of sIPNs has been round for greater than 100 years and has been utilized in automotive components, medical gadgets, molding compounds and engineering plastics. The normal concept is for a number of polymers to assemble round one other polymer scaffold in such a means that they grow to be interlocked. Even although the polymers will not be chemically bonded, they can’t be pulled aside and kind a brand new materials with properties better than the easy sum of its components.

Traditional strategies for manufacturing sIPNs sometimes contain producing the constituent components referred to as monomers and mixing them collectively in the proper chemical situations to regulate their meeting into massive networks in a course of referred to as polymerization.

“When it works, it’s a fantastic platform that can incorporate different functionalities into the self-assembled layer for biomedical or environmental applications,” stated Lingchong You, professor of biomedical engineering at Duke. “But the process is often not as biocompatible as you might want. So we thought why not use living cells to synthesize the second layer to make it as biocompatible as possible?”

In the new paper, Zhuojun Dai, a former postdoc in the You lab who’s now an affiliate professor at the Shenzhen Institute of Synthetic Biology, makes use of a platform that the lab has been creating for a number of years referred to as “swarmbots” to just do that.

The swarmbots are living cells that are programmed to supply organic molecules inside their partitions after which explode as soon as their inhabitants reaches a sure density. In this case, they’re programmed to supply monomers referred to as elastin-like polypeptides (ELPs) fused to useful options referred to as SpyTag and SpyCatcher. These two molecular buildings kind a lock-and-key system, permitting the ELPs to self-assemble right into a polymer chain when combined. As they develop, these polymers entangle themselves with the polymeric microcapsules containing the cells to kind sIPNs.

Each monomer can comprise a number of SpyTags or SpyCatchers and can be fused to proteins that generate a readout or have particular features. It’s type of like making a chain-link fence out of many tiny allure bracelets that have room for clasps and charms.

The researchers first program the cells to fill this accessorizable function with a fluorescent protein to show that the system can lock them into place. After that profitable demonstration, they flip their consideration to engineering a helpful drug delivery system with their new invention.

“You could replace the fluorescent marker with anything that has a function you want to feature,” stated You. “We decided to touch on antibiotics because it’s one of the other focuses of our lab.”

Beta-lactam antibiotics, corresponding to penicillin and its derivatives, are a few of the mostly used antibiotics in the world. They’re additionally usually overused and might have detrimental results corresponding to destroying the pure microbiome that lives inside our guts.

To display a technique through which their new cell-built sIPNs may very well be helpful, the researchers fill the accessorizable spot with beta-lactamase, which might degrade beta-lactam antibiotics. By injecting the newly functionalized sIPNs into mice, the researchers confirmed the platform may slowly launch the in any other case short-lived protecting molecule to assist the mice’s gut microbiomes keep at bay detrimental unwanted effects from the antibiotics.

“Nobody has used living cells as a factory to produce monomers in real-time for sIPNs before,” stated You. “The proof-of-principle demonstration shows that, not only can we fabricate these types of functional materials with live cells, but they can exhibit medically relevant functions.”

Story Source:

Materials supplied by Duke University. Original written by Ken Kingery. Note: Content could also be edited for type and size.

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