Stepping Strong Innovator Award recipients Su-Ryon Shin, PhD, and Indranil Sinha, MD, are working together to restore skeletal muscle mass and function using 3-D bioprinting

When a person suffers a traumatic muscle injury – from a motorcycle crash, for instance, or an incendiary device explosion – there is no way to regenerate the muscle that has been lost. When the injury heals, instead of new muscle, scar tissue forms. Plastic surgeon Indranil Sinha, MD, had the spark of an idea for how to help these patients. He thought that perhaps by injecting skeletal muscle stem cells at sites of injury, he could help patients regrow lost or damaged muscle. In 2014, Sinha received a Stepping Strong Innovator Award to test out his idea in the lab. But he encountered setbacks. The stem cells wouldn’t grow and muscle wouldn’t heal. Sinha investigated further and found that growth factors critical for regeneration simply weren’t present where they needed to be and without them, muscles couldn’t grow back. But as Sinha’s promising idea began to fizzle, something rekindled it.

The next year, Sinha joined a panel to judge the 2015 finalists for the Stepping Strong Innovator Awards competition. That’s where he heard BWH bioengineer Su-Ryon Shin, PhD, present on her work using 3-D bioprinting. Sinha sought her out immediately after the presentations, and the two started talking about their projects, and how they could help one another – and, ultimately, patients who had sustained muscle trauma injuries. Their conversation has continued ever since. In 2017, the two previous-award winners received an additional Stepping Strong grant of $100,000 to join forces to continue their work together.

Failure is the Mother of Success

On a recent winter afternoon, Shin arrived in Sinha’s office with happy news to share: one of her recent grant submissions had been scored. Sinha beamed and congratulated his collaborator, and told her he had good news too: his K76 had received a high score as well and the two shared a moment of relief and elation. But those moments of achievement stand out to both investigators in part because it has been so challenging to get here. For two years, Shin and Sinha have experienced an essential and often unspoken part of science: failure.

“Nothing in the first half of my Stepping Strong grant worked. Even when I saw Su-Ryon’s presentation, there was never a guarantee that bringing our ideas together would work either,” said Sinha. “But the Stepping Strong grant gave us the ability to try something no one had ever done before. It was a safe space in which to fail, and then try something new again. Together, we’ve been able to accomplish what neither of us could have done alone.”

Sinha speaks passionately about the needs of his patients. Unlike other diseases or injury where treatment exists but may be limited, for muscle trauma, there are currently no treatments. This means that investigators like Sinha and Shin cannot follow in the footsteps of others to build on their work; instead, they need to create entirely new approaches.

Shin is a trained bioengineer whose laboratory across the river in Cambridge includes state-of-the-art equipment, including a 3-D printer, for creating entirely new materials. These “scaffolds” can mimic the architectural structure of skeletal muscle, and be loaded with cells or molecules that can be slowly released in the body overtime.

Shin and her colleagues have designed many types of hydrogels – flexible, gel-like materials – over the years for medical applications. Based on discussions with Sinha, Shin has created a hydrogel loaded with stem cells as well as the growth factors whose absence Sinha had uncovered in his initial work. Their design process is iterative – initially, the hydrogel was too Jello-like for Sinha to suture it to a wound, so Shin redesigned it to be more like fabric.

Sinha and Shin visit one another’s laboratories and their teams have virtual meetings to share new insights across the lab and clinic. Other collaborations have sprung up across their teams too – Sinha is also working on a project with one of Shin’s colleagues on bone regrowth.

“We want to decrease that gap between clinicians and engineers,” said Shin. “The conversations I’ve had with the people I’ve met through the Stepping Strong network are so useful for me and have led to new funding and new collaborations.”

Early results from their work has been encouraging, although additional research is, of course, needed. In the meantime, Sinha, Shin and their collaborators have been able to leverage the data from the projects carried out using Stepping Strong Innovator Award funding to apply for federal grants, and have collectively garnered more than $5.6 million to continue their work.