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Biomaterial sticks to injured tendons and releases anti-inflammatory drugs

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A biomaterial that firmly adheres to injured tendons and helps them glide while slowly releasing anti-inflammatory drugs could lead to more effective tendon repairs.

A collaborative research team led by David Mooney, founding core faculty member at Harvard’s Wyss Institute for Biologically Inspired Engineering has developed a new biomaterial-based tendon therapy that addresses key challenges in the regeneration process.

The two-sided biomaterial firmly adheres to tendons with one of its specifically engineered surfaces, while allowing normal gliding of healing tendons with its opposite mechanically tough yet elastic surface.

Janus Tough Adhesives (JTAs) can also act as high-capacity drug depots, slowly releasing small molecules into tendon tissue to help facilitate healing.

David Mooney said: “JTAs with their combination of tissue-specific capabilities offer a new opportunity to overcome current insufficiencies in tendon regeneration across multiple types of injuries, and could help many patients regain more normal tendon functions and mobility.

“Our exceptional partnership with multi-disciplinary research groups at Novartis, besides providing highly complementary technical, modelling and experimental expertise, also enabled us, for the first time, to optimise and apply a Tough Gel Adhesive for the local delivery of a small molecule drug, which was one of our early goals.”

JTAs are the latest example of biomaterial-based adhesives developed by Mooney’s team as part of their Tough Gel Adhesive platform technology, which originally was inspired by the tough mucus produced by the Dusky Arion slug.

First-author and postdoctoral fellow Benjamin Freedman said these features make them highly useful as tissue sealants and wound dressings, as current adhesive materials don’t fulfil these essential requirements.

“To create Tough Gel Adhesives tailored to tendon regeneration, we forward-engineered an alginate-polyacrylamide-based hydrogel into a two-sided biomaterial, essentially, by modifying one of its surfaces with a sugar known as chitosan, which we showed allows firm bonding to tendons.

“The unmodified side could simultaneously enable gliding under the continued friction tendons that are exposed during movement.

“Within this ‘Janus-faced’ hydrogel, we then loaded a model drug that could be slowly released and chemically reduce inflammation.”

To show that JTAs’ resilience and elasticity protected tendons and enabled them to glide, the researchers attached them to the flexor tendons of human cadaveric hands, extending and flexing the wrists over hundreds of cycles: they noticed no signs of wear or disintegration.

Freedman said: “Importantly when we applied JTAs to ruptured patellar tendons of rats, they remained in place over their three-week implantation and facilitated tendon healing.

“They also reduced the formation of scars by 25 per cent, compared to surgically repaired tendons that we didn’t treat with JTAs.

Scarring normally accompanies healing as a result of inflammation and causes long-term loss of tendon functionality.

Using a patellar injury model in rats, the researchers investigated the effects of a corticosteroid, an anti-inflammatory model drug, that was encapsulated and released in a sustained manner from JTAs.

Using imaging technologies and molecular immunoassays, they showed that, in the tendons treated with corticosteroid-loaded JTAs, the inflammation subsided significantly faster.

Freedman and his co-workers are developing JTAs as off-the-shelf biomaterials for easy use by surgeons. All the biomaterial components in JTAs, including chitosan, which is obtained from the shells of crustaceans, are biocompatible and already used in other medical applications.

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