Traumatic muscle injury can be accompanied by volumetric muscle loss (VML), often leading to permanent loss of function. Until recently, experimental treatments that support muscle regeneration have faced several important limitations, including the challenge of delivering sufficient healing cells to the trauma site and the inability of traditional tissue transplants to adapt to the specific geometry of muscle defects.
A recent study led by Ngan F. Huang, Ph.D., senior author and associate professor of cardiothoracic surgery (research) in the Stanford Department of Cardiothoracic Surgery, highlights a unique approach her research team has developed to potentially address this issue and treat VML. Unlike traditional methods that use artificial frames or “scaffolds” to hold cells in place, Dr. Huang’s efforts focus on “scaffold-free” techniques. Using a simple mold-based approach, researchers grew dense muscle tissue with customizable geometries and sizes. This method allowed more healing cells to be packed into the affected area, where they self-organized within the mold and activated the regeneration process.
Dr. Huang’s paper, “Geometrically tunable scaffold-free muscle bioconstructs to treat volumetric muscle loss,” was featured on the cover of the journal. advanced healthcare materials, Published on March 10, 2026.
Custom “muscle patch” to treat injuries
In the body, muscles are held together by secreted extracellular matrix proteins. These proteins create a natural 3D scaffold structure that gives the tissue its shape, Dr. Huang said.
Many regenerative approaches focus on delivering cells to the site of trauma by constructing a “frame” or scaffold from biomaterials. So when researchers manipulate tissue in the lab to treat muscle injuries, they use biomaterials to mimic the extracellular matrix, Dr. Huang explained.
However, Dr. Huang and her team recognized a significant drawback to this approach. That means biomaterials occupy a significant volume. “Instead, we decided to omit the external biomaterial so that we could pump more healing cells into that volume,” she said.
She pointed out that even without biomaterials, cells can still secrete their own extracellular matrix naturally. Because traumatic muscle loss involves the loss of large numbers of cells within a defined amount of muscle damage, researchers recognized that recruiting sufficient numbers of cells is a challenge. Dr. Huang believed that removing the external biomaterial would free up more space for the cells to naturally form their own scaffold, allowing for the delivery of more healing muscle cells.
This scaffold-free tissue engineering approach has been tested in previous studies, but Dr. Huang and her team advanced it by creating custom “muscle patches” that can be adapted to any unique injury.
Our custom molding technology allows you to easily design any shape for your tissue structure, including shapes that form letters or words such as “Stanford.” ”
Ngan F. Huang, Ph.D., Stanford Associate Professor of Cardiothoracic Surgery (Research), Cardiothoracic Surgery
Important discoveries in the treatment of muscle injuries
Their research revealed several important discoveries regarding potential treatments for massive muscle damage. First, Dr. Huang noted that scaffold-free tissue allows cells to self-organize before implantation, resulting in gene and protein expression that resembles a more robust muscle identity. This is in contrast to traditional cell therapy strategies, where cells are detached from a dish and injected into the body as floating cells.
“We believe that the preformed cell-to-cell interactions provided by these scaffold-free tissues allow cells to communicate with each other, ultimately resulting in more effective muscle cells,” said Dr. Huang.
Another important finding showed that scaffold-free structures can be geometrically adjusted upon contact and integrated with the damaged area. This provides proof of principle that smaller modular shapes can be integrated into larger, more complex shapes.
A vision for the future of muscle repair
Researchers in Huang’s lab hope this work will have major clinical benefits. They envision using this strategy to build a library of scaffold-free tissue shapes that can serve as building blocks.
In the future, Dr. Huang believes it will be possible to combine this technology with robotic assistance, traditional clinical imaging modalities, and AI. With robot assistance, you can input the shape of your muscle injury and design a map to fill the missing area with a customized shape.
“This allows us to generate more complex shapes,” Dr. Huang said. “From a scalability perspective, modular shapes form building blocks to larger, more complex shapes that can be customized for each patient.”
In this scenario, robotic assistance allows precise placement of various shapes, eliminating the need for a surgeon to perform precise placement. “Of course, a surgeon is still needed to supervise the robot and intervene if necessary,” she says.
The figure shows the biofabrication of scaffold-free customizable modular shapes for tissue engineering.
Future directions in the treatment of muscle loss
Regarding the next steps and direction of this research, Dr. Huang and her team will focus on integrating modular shapes to build more complex shapes. Other organizational components are also added. Muscles are made up of many different types of cells, including blood vessels and nerves. They also plan to apply the technique to modular shapes that incorporate blood vessels, nerves, and muscle structures to achieve more complex tissues.
Dr. Huang thinks this approach could be applied to other areas of muscle regeneration. “Although this strategy is demonstrated here for muscle defects, we envision this modular tissue construction approach being applied to cardiovascular tissues such as the heart in the future,” she said.
This publication is a collaboration with researchers and members of the Stanford Heart and Vascular Institute and the VA Palo Alto Healthcare System. Authors of this paper include Dr. Bugra Ayan; Gaoxian Chen, Ph.D. Dr. Ishita Jain. Xia Chen, MD. Gladys Chan. caroline fu. Renato Reyes. and Dr. Beu P. Oropeza.
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Reference magazines:
Ayan, B. Others. (2025). Geometrically adjustable scaffold-free muscle bioconstructs to treat volumetric muscle loss. Advanced healthcare materials. DOI: 10.1002/adhm.202501887. https://advanced.onlinelibrary.wiley.com/doi/10.1002/adhm.202501887
