Engineered Stem Cell Nano-mesh Regrows Rotator Cuff Tendon

A way to regenerate rotator cuff tendons after they’ve been torn that makes a stronger repair has been found by a team of researchers from the University of Connecticut. Rotator cuff problems are common, with about two million people afflicted and about 300,000 rotator cuff repair surgeries every year in the US.

Surgeons have developed many techniques to reconnect the tendon to the bone. The problem is that often they don’t stay reconnected.

Up to 60% of the time after surgery, there’s a re-rupture, according to Dr. Cato Laurencin, Van Dusen Distinguished Professor of Orthopaedic Surgery at U Conn Health. And that means more surgery, or learning to live with reduced mobility in the joint. Orthopaedic surgeons struggle with this constantly and would love to have a better way.

Stem Cell Nano-mesh

Every time you throw a ball, swing a golf club, reach for a jar on a shelf, or cradle a baby, you can thank your rotator cuff. This nest of tendons connecting your arm bone to your shoulder socket is a functional marvel, but it’s also prone to tearing.

Using a nano-textured fabric matrix seeded with stem cells, Laurencin and his colleagues were able to get torn rotator cuff tendons to regenerate in animals.

Not only did the tendons wrapped in the fabric make a better attachment to the bone, they were stronger overall, with a cell structure that looked more like natural, undamaged tissue. Tendons repaired with a purely surgical technique healed with a more disorganized cell structure, which made the tendon itself weaker.

Non-augmented and augmented rat supraspinatus repair model (A) Modified MasonAllen stitch described by Soslowsky. Purple indicates suture, * indicates areas of stress. (B) Integrated matrix augmentation model for supraspinatus tendon repair. Green indicates the side of cell seeding in matrix/rMSC group. Credit: M. Sean Peach, et al/PLOS

The combination of the “nano-mesh” with stem cells seems to be critical. Surgeons will sometimes inject stem cells into rotator cuff repairs, but results from this technique are mixed. Stem cells alone don’t necessarily stick around at the surgery site.

Adding the mesh changes that.

The mesh, made of a nanostructured polymer combining polylactic acid (PCL) and polyphosphazene (PNEAmPh) — pioneered in Laurencin’s laboratory — provides an attractive habitat for the stem cells to hunker down. Once they settle into the rotator cuff location, the stem cells began sending out signals directing other cells to align and grow into tendon tissue.

Rotator Cuff Tissue Regeneration

Insertion morphology of repair

Insertion morphology of repair, matrix augmentation and matrix/rMSC repair of rat supraspinatus tendons.
Native (CON) tendons (A) demonstrate a gradual transition from parallel oriented collagenous tendon tissue to bone with a cartilage intermediate. Repair (R) (B) and matrix augmented (R+S) (C) insertions have an abrupt transition. Matrix/rMSC repair (R+S+C) (D) insertions demonstrate a transition and organization similar to the intact tendon. Representative samples at 12-weeks post-surgery stained with Masson’s trichrome. Matrix/sutures are located on the surface plane above the tendon-bone insertion and are present at both 6 (not shown) and 12-weeks. Yellow arrow indicates the bone-tendon axis. Scale bars 200 μm. Credit: M. Sean Peach, et al, PLOS

Images taken at six and twelve weeks in animals show that torn rotator cuff tissue reorganizes under the influence of the matrix and stem cells. Once the tendon is fully regenerated the polymer matrix can dissolve.

“We hope to use this technology to create new methodologies in rotator cuff repair,” Laurencin says.

And if the polymer mesh plus stem cell technique proves durable in human rotator cuff tendons, Laurencin won’t stop there.

“Being able to regenerate complex soft tissues like the rotator cuff is an important step, but we have even bigger goals,” Laurencin says.

Their results have already laid the groundwork for regenerating tendons in other joints, including the knee. His long-term project is called the Hartford Engineering a Limb Project or H.E.A.L. Funded by a National Institutes of Health Pioneer Award, an Emerging Frontiers Grant from the National Science Foundation, and grants from the state of Connecticut, his project aims to eventually regrow entire joints and limbs.

Peach MS, Ramos DM, James R, Morozowich NL, Mazzocca AD, Doty SB, et al. (2017)
Engineered stem cell niche matrices for rotator cuff tendon regenerative engineering
PLoS ONE 12(4): e0174789. doi:10.1371/journal.pone.0174789

Image: University of Connecticut

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