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Mechanically-induced regeneration

Skeletal muscle and satellite cells are sensitive to biophysical and microenvironmental cues, and there is evidence that physical manipulation of damaged muscle may promote recovery. David Mooney’s lab has used biphasic ferrogel scaffolds to create a system capable of massage-like compressions to promote muscle regeneration after severe injury. These scaffolds are implanted at the site of muscle injury, and an exterior magnetic field stimulates uniform cyclic compressions. Use of this system in a mouse model of severe muscle damage led to reduced fibrous capsule formation around the implants when compared to no treatment, as well as when compared to a similar compression treatment applied with an external pressure cuff. It also led to reduced fibrosis and inflammation in the injured muscle, enhanced muscle regeneration, and increase in mean muscle fiber size. Functionally, mice treated with cyclic mechanical compressions exhibited an increase in maximum contractile force of the injured muscle after two weeks. The ferrogels also exhibited an immunomodulatory role when stimulated, showing reduced levels of muscle-infiltrating inflammatory cells and macrophages.

 

Applications

Biphasic ferrogel scaffolds showed utility in a mouse model severe skeletal muscle injuries, which can lead to fibrosis, scarring, and loss of function. Currently, there is no therapeutic intervention that allows for a full functional restoration of severely injured muscle tissue. The improvement in muscle fiber size using this method, however, was of the same order of magnitude as cell and drug delivery approaches, and the functional gain was comparable to that of growth factor therapies. These biologic-based therapies, however, are limited by loss of local concentration, growth factor bioactivity, and regenerative potential associated. This provides a biologic-free system for a simple but effective alternative to cell-based therapies. Incorporation of cyclic mechanical compressions into existing drug and cell delivery systems could also potentially lead to new and better combination therapies. It could be used in other tissues and diseases for mechanically driven regeneration, and find a more broad utility in the field of regenerative medicine.

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