3D nanostructures improve skeletal muscle regeneration

May 28, 2019

By Megan Mayerle, PhD

Our muscles get stronger though repeated cycles of injury and repair. Exercise damages muscle, but at the same time activates muscle stem cells that differentiate into new skeletal muscle fibers, repairing and strengthening the tissue. However sometimes the amount of damage done to muscle is too much, and, unable to properly heal, chronically inflamed scar tissue forms. In order to heal from this type of damage, the body must not only produce new skeletal muscle cells, it must also make sure that these cells orient properly to contract.

In a study recently published in Communications Biology, Stanford Cardiovascular Institute researchers Karina Nakayama, Ngan Huang, and colleagues describe a method to fabricate skeletal muscle using spatially patterned bioengineered scaffolds. These scaffolds help newly formed skeletal cell muscles align, and when implanted into a damaged area, help mice recover from injury.

The researchers created aligned nanofibrillar scaffolds and then seeded them with myoblasts and endothelial cells, the cell types that make up skeletal muscle tissue. The nanofibrillar scaffolds organized the cells, producing long skeletal muscle myotubules capable of contracting strongly and consistently. Alignment also affected cellular gene expression, inducing differential transcriptional pathways that may regulate how engineered muscle behaves.

To test this engineered muscle, the scientists injured mice and then transplanted their aligned engineered skeletal muscle to the site of injury. Encouragingly, the aligned tissue integrated into the site of injury without significant scarring. It also aided in tissue revascularization, which is critical for recovery from injury.

This method shows great translational promise, as the researchers were also able to show that human cells aligned on bioengineered scaffolds functioned similarly to the mouse cells and highlights the importance of how cells are positioned in 3D in regenerative medicine approaches.

Stanford researchers who contributed to this study include Karina H. Nakayama, Marco Quarta, Patrick Paine, Cynthia Alcazar, Ioannis Karakikes, Victor Garcia, Oscar Abilez, Thomas Rando, and Ngan Huang. Funding was provided by the Alliance for Regenerative Rehabilitation Research and Training (AR3T) Award P2CHD086843, NIH grants R01 HL127113, R01 HL142718, K99 HL136701, and P01 AG036695, the California Institute of Regenerative Medicine, the Department of Defense, and the Department of Veterans Affairs (REAP and RR&D Merit Reviews, grants 1I01BX002310 and 1I01BX004259).

Dr. Karina H. Nakayama

Dr. Ngan Huang