August 2021

Bioengineering Approach Shown to Regenerate Functional Muscle

The dECM-MA derived from porcine skeletal muscles is combined with PVA fibrillation, which provides the topographical cues for proper cellular alignment when bioengineering rat muscles. Image courtesy of Sang Jin Lee.

Researchers from Wake Forest Institute for Regenerative Medicine and 2 South Korean institutions—Sungkyunkwan University and Chonnam National University—have developed an efficient technique for muscle regeneration and functional restoration in injured rats. The group expanded on a method they previously developed using muscle-specific materials derived from an organism’s tissues (dECM-MA) to construct bioinks, which are materials used for 3D printing tissue.

The researchers combined dECM-MA from pigs’ skeletal muscles with poly(vinyl alcohol) (PVA) fibrillation, a technique that provides cues to the molecules in the bioink to guide them to their target tissue and ensure they are properly aligned. By optimizing the PVA to enable stable, viable, well-aligned cell structures, the researchers were able to improve muscle regeneration and function restoration.

“One major benefit over previous approaches is the self-alignment of muscle cells in the 3D structure without any supporting components,” said Wake Forest Associate Professor Sang Jin Lee, PhD. “This could allow us to fabricate more clinically relevant bioengineered muscle constructs.”

The technique was tested on rats with injured foot muscles. When compared with uninjured rats of the same age and rats with the same injury but no treatment, the rats treated with the muscle regeneration technique showed over 80% muscle function restoration. Moreover, the bioengineered muscles integrated well with the rats’ neural and vascular systems. These promising results suggest combining dECM-MA with PVA is a clinically feasible method for achieving large-scale tissue regeneration, provided the damage does not extend to nearby cells from which the tissue materials can be derived.

“This advanced bioprinting approach for bioengineering functional skeletal muscle constructs may be an effective therapeutic option for treating extensive muscle defect injuries with accelerated innervation and vascularization,” Lee said.

Since the technique requires cells from the patient, the group anticipates some hurdles in translating the methodology for human subjects, where it will be especially beneficial for systems that require cellular-level alignment, like cardiac and skeletal muscles. In the meantime, they plan to continue preclinical trials on larger, more clinically relevant muscle constructs in larger animals, such as rabbits, dogs, and pigs.

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