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The materials, known as semi-interpenetrating polymer networks (SIPNs), were produced at Duke University in North Carolina. The new approach could make versatile materials for biologically compatible applications such as time-delayed drug delivery systems.
The concept of SIPNs has been around for more than 100 years, and the materials have been used in automotive parts, medical devices, moulding compounds and engineering plastics. The materials include one or more polymers assembled around another polymer scaffold, in such a way that they become interlocked without chemical bonding, meaning they cannot be pulled apart.
Conventional manufacturing methods involve producing the constituent monomers, then mixing them together in the right chemical conditions to control their assembly into large networks, in a process called polymerisation.
“When it works, it's a fantastic platform that can incorporate different functionalities into the self-assembled layer for biomedical or environmental applications,” said biomedical engineer Professor Lingchong You. “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 research, Zhuojun Dai – a former researcher in You’s lab and current associate professor at the Shenzhen Institute of Synthetic Biology in China – used ‘swarmbots’ to do just that. The living cells were programmed to produce monomers called elastin-like polypeptides (ELPs) within their walls, and to explode once they reached a certain density. The ELPs self-assemble into a polymer chain when mixed, entangling themselves within the polymeric microcapsules containing the cells to form SIPNs.
The team first demonstrated the technique by integrating a fluorescent protein, proving the system can lock substances into place. After the successful demonstration, they turned their attention to engineering a useful drug delivery system.
“You could replace the fluorescent marker with anything that has a function you want to feature,” said You. “We decided to touch on antibiotics, because it's one of the other focuses of our lab.”
Beta-lactam antibiotics, such as penicillin and its derivatives, are some of the most commonly used antibiotics in the world. They are also often overused, and can have negative effects such as destroying the natural microbiome within our intestines.
To demonstrate one way in which cell-built SIPNs could be useful, the researchers filled the materials with beta-lactamase, which can degrade beta-lactam antibiotics. By injecting the newly ‘functionalised’ SIPNs into mice, the researchers showed the platform could slowly release the otherwise short-lived protective molecule to help gut microbiomes ward off negative side effects from antibiotics.
“Nobody has used living cells as a factory to produce monomers in real-time for SIPNs before,” said 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.”
The research was published in Nature Communications.
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