Making More Muscle – Innovating with Bioconstructs
by Adrienne Mueller, PhD
May 15, 2025
Traumatic injury frequently causes irreparable loss of tissue. Our body’s ability to regenerate lost tissue is limited. Stem cells – cells that have the potential to become any cell type – play a crucial role in tissue repair. Once injury occurs, the local muscle tissue produces a sequence of specific factors that direct the regeneration of damaged muscle by inducing muscle stem cells to grow and change as needed. However, when severe traumatic injuries occur, this process struggles to cope.
Our bodies repair systems cannot handle large amounts of muscle loss – which often results in tissue deformity and functional deficits. A strategy to overcome this problem and promote tissue generation is to transplant new muscle stem cells into the damaged tissue. However, previous efforts to implement this therapy have struggled, because the implanted cells do not grow or develop sufficiently.
Combining stem cells with novel biomaterials can help replace lost muscle tissue after traumatic injury.
Biomaterials are a promising new approach to improve tissue recovery using stem cells. Previous work has already shown that transplanting muscle stem cells in a matrix that mimics that of our own bodies improves the function of the transplanted cells. However, it’s not just the environment that matters for regeneration to flourish – it’s also the cues the stem cells receive, and when they are received. Stem cells need to be directed when to become active, when to grow, and when to develop into more specialized cells. These instructive cues are provided by growth factors, but delivering a single shot of growth factors at the site of injury often does more harm than good – because a large dose at a single time point is more like an overdose than the slow spread of growth factors during natural injury repair.
Although previous work has also attempted to allow the slow release of growth factors using media such as hydrogels, precise manipulation of timing has remained elusive.
In a recent study led by Di Wu, PhD, Ngan Huang, PhD, and Thomas A. Rando, MD, PhD, and published in Nature Materials, a team of investigators created a bioconstruct that orchestrates the release growth factors in a specific sequence and timing that is tailored to direct muscle regeneration.
The bioconstruct is made of a material that mimics the matrix found outside cells in our own bodies and is engineered to contain nanocapsules – thin layers of polymers - that allow a staged release growth factors to promote the growth and specialization of muscle stem cells. The investigators further showed in mice that use of their new bioconstruct with implanted stem cells enhances the formation of muscle fibers and new cells in damaged tissue - and even improved innervation and motor function. Additionally, the investigators then went the extra mile to assess the translational potential for their bioconstruct – would it work with human stem cells? And it does.
Overall, this groundbreaking study clearly shows the translational potential of phased-release bioconstructs for repairing traumatic injuries. Further, this study serves as a demonstration of the bioconstruct platform for directing stem cell behavior that can be extended to other translational applications and future therapies.
Additional Stanford Cardiovascular Institute-affiliated investigators who contributed to this work include Caroline Hu, Soochi Kim, Abhijnya Kanugovi, Joshua R. Wheeler, Iman Fathali, and Joseph B. Shrager.
Dr. Di Wu
Dr. Ngan Huang
Dr. Thomas Rando