Initial demonstration builds drug delivery system that protects gut microbiome from antibiotics

Biomedical engineers at Duke University have demonstrated that a class of interwoven composite materials called semi-interpenetrating polymer networks (sIPNs) can be produced by living cells. The approach could make these versatile materials more biologically compatible for biomedical applications such as delayed drug delivery systems.

The research appears online June 8 in the journal Nature Communication.

The concept of SIPN has been around for over 100 years and has been used in automotive parts, medical devices, molding compounds and engineering plastics. The general idea is that one or more polymers assemble around another polymer scaffold in such a way that they fit together. Even though the polymers are not chemically bonded, they cannot be separated and form a new material with properties greater than the simple sum of its parts.

Traditional methods of making SIPNs generally involve producing the building blocks called monomers and mixing them under the right chemical conditions to control their assembly into large networks in a process called polymerization.

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

In the new article, Zhuojun Dai, a former post-doctoral fellow at the You lab who is now an associate professor at the Shenzhen Institute for Synthetic Biology, uses a platform the lab has been developing for several years called “swarmbots” to do just that. that.

Swarmbots are living cells that are programmed to produce biological molecules inside their walls and then explode once their population reaches a certain density. In this case, they are programmed to produce monomers called elastin-like polypeptides (ELP) fused to functional characteristics called SpyTag and SpyCatcher. These two molecular structures form a lock and key system, allowing PELs to self-assemble into a polymer chain when mixed together. As they grow, these polymers intermingle with the polymeric microcapsules containing the cells to form sIPNs.

Each monomer can contain multiple SpyTags or SpyCatchers and can also be fused to proteins that generate a read or have specific functions. It’s a bit like making a chain link fence out of many small charm bracelets that have room for clasps and charms.

The researchers first program the cells to fulfill this accessorizable characteristic with a fluorescent protein to prove that the system can lock them in place. After this successful demonstration, they turn to designing a useful drug delivery system with their new invention.

“You can replace the fluorescent marker with anything that has a function that you want to present,” You said. “We decided to tackle antibiotics because it is one of the other axes of our laboratory.”

Beta-lactam antibiotics, such as penicillin and its derivatives, are among the most commonly used antibiotics around the world. They are also often overused and can have negative effects such as destroying the natural microbiome that lives in our intestines.

To demonstrate one way their new cellular sIPNs could be useful, the researchers are filling the accessorizable spot with beta-lactamase, which can degrade beta-lactam antibiotics. By injecting the newly functionalized sIPNs into mice, the researchers showed that the platform could slowly release the otherwise short-lived protective molecule to help the gut microbiomes of mice avoid negative side effects of antibiotics.

“No one has used living cells as a factory to produce real-time monomers for sIPNs before,” You said. “The proof-of-principle demonstration shows that not only can we make these types of functional materials with living cells, but they can exhibit medically relevant functions.”

Source of the story:

Materials provided by duke university. Original written by Ken Kingery. Note: Content can be changed for style and length.


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