Silicon nanochip could treat traumatic muscle loss

Tissue nanotransfection is a minimally invasive nanochip device that can reprogram tissue function by applying a harmless electric spark to deliver specific genes in a fraction of a second.

A new study, published in Nature Partner Journals Regenerative Medicine, tested tissue nanotransfection-based gene therapy as a treatment, with the goal of delivering a gene known to be a major driver of muscle repair and regeneration. They found that muscle function improved when tissue nanotransfection was used as a therapy for seven days following volumetric muscle loss in rats. It is the first study to report that tissue nanotransfection technology can be used to generate muscle tissue and demonstrates its benefit in addressing volumetric muscle loss.

Volumetric muscle loss is the traumatic or surgical loss of skeletal muscle that results in compromised muscle strength and mobility. Incapable of regenerating the amount of lost tissue, the affected muscle undergoes substantial loss of function, thus compromising quality of life. A 20 percent loss in mass can result in an up to 90 percent loss in muscle function.

Current clinical treatments for volumetric muscle loss are physical therapy or autologous tissue transfer (using a person's own tissue), the outcomes of which are promising but call for improved treatment regimens.

"We are encouraged that tissue nanotransfection is emerging as a versatile platform technology for gene delivery, gene editing and in vivo tissue reprogramming," said Chandan Sen, director of the Indiana Center for Regenerative Medicine and Engineering, associate vice president for research and Distinguished Professor at the IU School of Medicine. "This work proves the potential of tissue nanotransfection in muscle tissue, opening up a new avenue of investigational pursuit that should help in addressing traumatic muscle loss. Importantly, it demonstrates the versatility of the tissue nanotransfection technology platform in regenerative medicine."

Sen also leads the regenerative medicine and engineering scientific pillar of the IU Precision Health Initiative and is lead author on the new publication.

The Indiana Center for Regenerative Medicine and Engineering is home to the tissue nanotransfection technology for in vivo tissue reprogramming, gene delivery and gene editing. So far, tissue nanotransfection has also been achieved in blood vessel and nerve tissue. In addition, recent work has shown that topical tissue nanotransfection can achieve cell-specific gene editing of skin wound tissue to improve wound closure.

Other study authors include Andrew Clark, Subhadip Ghatak, Poornachander Reddy Guda, Mohamed S. El Masry and Yi Xuan, all of IU, and Amy Y. Sato and Teresita Bellido of Purdue University.

This work was supported by Department of Defense Discovery Award W81XWH-20-1-251. It is also supported in part by NIH grant DK128845 and Lilly Endowment INCITE (Indiana Collaborative Initiative for Talent Enrichment).