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Bio-Based Material Shown to Aid Tendon Repair

Dusky Marion sea slug

Dusky arion sea slug (Distant Hill Gardens, Flickr. https://www.flickr.com/photos/59898141@N06/15034182409)

3 Jan. 2022. Academic and industry researchers demonstrated in lab animals a tough material derived from natural sources that speeds repair of injured tendons. A team from the Wyss Institute for Biologically Inspired Engineering at Harvard University and Novartis Institutes for BioMedical Research or NIBR, part of global drug maker Novartis, describe their material and experiments in today’s issue of the journal Nature Biomedical Engineering (paid subscription required).

Tendons are the soft tissue connecting muscles to bones that allow free movement of joints. With advancing age, however, tendons can degenerate and break down from wear and tear, and as a result, older individuals are more susceptible to tendon injuries. Likewise, tendons can tear from intense strain of athletics, with tendons in the shoulder, hand and forearm, knee, and ankle (Achilles tendon) susceptible to injury.

Researchers in the Wyss Institute biomedical engineering lab of David Mooney study materials that aid in regeneration of cells and tissue. Among those materials is a hydrogel, a water-based polymer, inspired by a tough, resilient substance released by the dusky arion sea slug. That hydrogel, with physical properties resembling human cartilage, is made from two types of biocompatible polymers: alginate from seaweed used today as a food thickener, and and polyacrylamide used in water treatment plants and soft contact lenses.

For repairing tendons, the team needed to give the material the ability to both stick tightly to an injured tendon, and enable free movement of the joint. Postdoctoral researcher and first author Benjamin Freedman explains in a Wyss Institute statement, “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.”

Drug delivery added for tendon repair

Freedman and colleagues first tested the two-sided material they call Janus tough adhesives, or JTAs, in the lab with tendons and joints from pigs and human cadavers, simulating life-like conditions. In the next series of tests, the researchers applied the material to live lab rats, with ruptured patellar tendons in the knee. Freedman says JTAs “remained in place over their three-week implantation and facilitated tendon healing. They also reduced the formation of scars by 25 percent, compared to surgically repaired tendons that we didn’t treat with JTAs.”

The researchers tested JTAs for one more property, the ability to deliver drugs to the injury site. The team added an anti-inflammatory corticosteroid drug to JTAs on some of the injured lab rats, with inflammation in the recipients of drug-aided JTAs subsiding faster than rats receiving JTAs without the drugs.

The capability for sustained release of drugs to injuries is one of the interests for Novartis in the technology. “The combination of active pharmaceutical ingredients with Janus tough adhesives,” notes Michaela Kneissel who heads musculoskeletal disease research at NIBR, “has the potential to become a promising avenue for such an adaptive therapy, with release and activity of pharmaceutical ingredients gated by the JTAs to better facilitate tendon repair and regeneration.”

As reported by Science & Enterprise in March 2018, Novartis previously licensed a biomaterial for drug delivery from Mooney’s lab at Wyss Institute. In this case, the company acquired rights to a biocompatible material designed for delivery of treatments that invoke the immune system to fight cancer.

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