[Image above] Tears in the rotator cuff are one of the most common injuries related to tendons and muscles in the adult population. Regenerative engineering methods may help improve treatment of such tears. Credit: Pexels
Of the hundreds of muscles that make up a human’s muscular system, the rotator cuff is notorious as one of the most common areas for tendon-and-muscle-related injuries in adults.
The rotator cuff is a group of muscles and tendons that surround the shoulder joint. They keep the head of the upper arm bone firmly within the shallow socket of the shoulder.
An estimated two to four million people in the United States experience some type of rotator cuff problem every year, particularly partial or complete tears that separate the tendons from the bone.
Following a tear, the tendons and muscles will begin to retract, and associated degenerative changes will begin to set in, including muscle atrophy, fat accumulation, and fibrosis formation.
There currently is no way to reverse the muscle degenerative changes, so most rotator cuff repair procedures focus solely on reattaching the tendons to the shoulder joint. But the success of these surgeries is hindered by the remaining fat accumulation and muscle atrophy, which increase the chances of retear.
Thus, developing regenerative engineering approaches to treat muscle degeneration is essential to improve treatment and long-term recovery success for patients with rotator cuff tears.
In a recent paper published in Proceedings of the National Academy of Sciences, University of Connecticut School of Medicine researchers led by Cato Laurencin, ACerS Fellow and Albert and Wilda Van Dusen Distinguished Professor of Orthopaedic Surgery, presented a new regenerative engineering method based on graphene for treating rotator cuff tears.
They explain that graphene offers several potential benefits to muscle regeneration.
- Promotes myogenesis. Myogenesis is the formation of skeletal muscular tissue. Several studies indicate that electroconductive materials like graphene can significantly promote myoblast proliferation and differentiation, even without the use of external electrical stimulation. (Myoblasts are the embryonic precursors of muscle cells.)
- Increases intracellular calcium levels. Studies show that high concentrations of calcium ions stimulate myogenesis, but it can reduce intracellular calcium levels, which inhibits myoblast differentiation and proliferation. Electroactive materials like graphene may help increase intracellular calcium levels.
- Inhibits lipid formation. Several studies suggest a graphene matrix may have an inhibitory effect on lipid (fat) formation.
“These effects provide strong motivations for using graphene matrices for reducing fat formation after massive rotator cuff tendon tears,” the researchers write.
Using a fiber production method called electrospinning, they fabricated an aligned nanofibrous structure composed of graphene nanoplatelets and poly(l-lactic acid). They then tested the potential of this mesh by trying to grow muscle on it in a petri dish.
The petri dish experiment proved very successful regarding all three potential benefits listed above.
- The researchers observed alignment of myoblasts along the nanofiber direction, which suggests the matrices induced cellular orientation. This alignment provides an essential topographical cue to enhance myoblast growth and differentiation, in addition to the electrical cues. These combined cues resulted in high differentiation and maturation of myoblasts into myotubes (multinucleated fibers).
- They detected higher intracellular calcium ion levels in myoblasts on the graphene-polymer matrix, which correlated with the enhanced myotube formation.
- They confirmed that graphene suppressed lipid production, which suggests the inhibitory effect of graphene on adipogenesis (the formation of fat-laden cells).
Following this experiment, the researchers investigated the efficacy of using the graphene-polymer matrix to treat rats who had chronic rotator cuff tears with muscle atrophy.
Overall, histological analysis showed the matrix implantation induced a reversal of muscle degeneration. Additionally, histological staining of the internal organs showed no obvious tissue damage, inflammation, toxicological effects, or any material accumulation in the organs at 8 and 16 weeks after matrix implantation.
Finally, the researchers used histological staining to investigate the effect of matrix implantation on tendon healing. They found that addressing the muscle degeneration reduced retraction stress on the tendon and improved tendon healing.
“The [current] goal of massive rotator cuff tendon tear treatment is to improve tendon morphology and tensile properties. Here, we showed that reversing rotator cuff muscle degeneration is the real key to addressing the real problem,” the researchers conclude.
A UConn press release reports that the next step is studying the matrix in a large animal. Eventually, the researchers hope to develop the technology in humans.
This work was funded by NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant No. DP1AR068147 and National Science Foundation Emerging Frontiers in Research and Innovation Grant No. 1332329.
The paper, published in Proceedings of the National Academy of Sciences, is “Muscle degeneration in chronic massive rotator cuff tears of the shoulder: Addressing the real problem using a graphene matrix” (DOI: 10.1073/pnas.220810611).