Professor’s Big-Picture Ideas for Tissue Engineering Backed by Prestigious AFIRM III Award

George Christ is not the kind of person to hang back and work on a portion of a puzzle. Christ, a professor of biomedical engineering and orthopedic surgery at the University of Virginia, is drawn to tackle large challenges in his field and complete them as quickly as possible—especially because his work in regenerative medicine has the potential to transform the lives of soldiers and accident victims crippled by massive muscle injury.

It is because of the breadth of his vision that the Department of Defense awarded him a prestigious AFIRM III grant from the Armed Forces Institute of Regenerative Medicine to develop solutions to devastating muscle loss injuries.

  • George Christ, tissue engineering expert

    In a new AFIRM III grant from the Armed Forces Institute for Regenerative Medicine, George Christ is developing a system for regenerating muscle tissue that functions and behaves like the tissue it replaces. Christ is a professor of biomedical engineering and the Mary Muilenburg Stamp Professor of Orthopaedic Research at the University of Virginia.

  • Collage photo of three professors who won a grant from BioFabUSA, a non-profit research organization dedicated to rapidly advancing biomanufacturing technologies

    Christ announced this year a new partnership with the Advanced Regenerative Manufacturing Institute’s BioFabUSA program for a new tissue foundry, a custom-designed tissue incubation system, or bioreactor, that will be used to automate the growth of muscle stem cells into implantable tissue patches. Here he is pictured here with project partners UVA Engineering professors Gavin Garner, left, and Shayn Peirce-Cottler, center.

  • George Christ, tissue engineering expert in the lab

    Christ is also the is the recipient of a Coulter Translational Research Partnership-funded project to define the ideal oxygen and pH requirements in a tissue manufacturing environment.

Making the Vision a Reality

Christ also is a recent recipient of a Coulter Translational Research Partnership-funded project to define the ideal oxygen and pH requirements in a tissue manufacturing environment. He also announced this year a new partnership with the Advanced Regenerative Manufacturing Institute’s BioFabUSA program for a new tissue foundry, a custom-designed tissue incubation system, or bioreactor, that will be used to automate the growth of muscle stem cells into implantable tissue patches.

An expert in tissue engineering, Christ understands the complexity of the biology needed to regenerate and replace damaged or destroyed tissue. He also realizes that exceptional expertise and persistence are required to translate discovery into practical therapy.

He knows that achieving a project of this scope and ambition transcends the ability of any single person.

Six years ago, Christ moved his research program to the University of Virginia because the biomedical engineering community gave Christ the platform he needed to engage world-class colleagues like professors Silvia Blemker and Shayn Peirce-Cottler; to recruit innovators from leading universities and bioscience companies; and to enlist specialists from the world of regulation and manufacturing.

“With its emphasis on translation, UVA encourages thinking in terms of end-to-end solution,” Christ said.

The Case for Urgency

The signature weapon of the wars in Iraq and Afghanistan is the improvised explosive device. These roadside bombs often produce extensive muscle damage that far exceeds the body’s regenerative capacity. The wounds, known as volumetric muscle loss injuries, are both disfiguring and debilitating.

On the civilian side, gunshot wounds, car accidents, equipment injuries, rotator cuff injury and genetic anomalies like cleft palate leave similar losses that require bridging with healthy, functional muscle tissue. Because there is no viable way to replace so much missing tissue, people have no choice but to live with their wounds and disabilities.

For Christ, this is not an acceptable state of affairs. Motivated by society’s common debt of gratitude to wounded veterans and the potential to bring these advances to the general population, he approaches the challenge with a sense of urgency.

“It can take as long as 20 years to bring a new regenerative technology to market,” he said. “We are trying to cut the process to seven to 10 years at most.”

"It can take as long as 20 years to bring a new regenerative technology to market. We are trying to cut the process to seven to 10 years at most."

George Christ, Professor of biomedical engineering and orthopedic surgery

A Trusted Partner in Leading Multi-Institution, Multi-Investigator Projects

The strategies Christ has devised to accelerate this process are clearly on display in his latest grant from the Armed Forces Institute for Regenerative Medicine, a $2 million AFIRM III award. In addition to bringing his own expertise to bear, Christ has assembled a group of outstanding researchers with mutually reinforcing expertise in regenerative medicine to explore novel approaches to treatment.

Christ’s ability to call on such eminent engineers and scientists and the selection of the UVA team for an AFIRM III awards speak to the strength of the regenerative medicine program that he has catalyzed here.

“To be selected to be part of AFIRM III is quite an honor,” Christ said. “It speaks to the decade or so that we have already committed to developing and evaluating novel and more effective tissue engineering and regenerative medicine platforms, more recently incorporating the computational modeling that colleagues Silvia Blemker and Shayn Peirce-Cottler are pioneering, as well as our expanding network of collaborators around the globe.”

"My goal is to build completely native tissue, and to do so, I will need the best materials and the best people available at every step of the way. That kind of multidisciplinary collaboration is something that UVA has always done well."

George Christ, Professor of biomedical engineering and orthopedic surgery

Building Muscle Tissue that Can Bridge a Large Wound

At the core of the AFIRM III grant is the group that Christ has gathered to build a system for regenerating muscle. It includes Lisa Larkin, a professor of biomedical engineering at the University of Michigan; Kevin Healy, a professor of bioengineering at the University of California at Berkeley; and Luke Burnett, CEO and chief science officer at KeraNetics, an advanced biomaterials company in Winston-Salem, North Carolina.

Larkin is creating what she calls skeletal muscle units to replace lost tissue in large wounds. These are a composite engineered tissue product. They consist of skeletal muscle with bone tendon ends and functional interfaces between muscle and tendon (myotendinous junction) and tendon and bone (enthesis). However, successful repair using Larkin’s muscle units has been limited by scarring from fibrosis.

Healy and Burnett have each developed a therapeutic hydrogel that could mitigate fibrosis and promote healing. Working with Christ, Healy and Washington State University collaborator Glenn Prestwich have developed Volumatrix™, a hyaluronic acid-based hydrogel that embodies material features more favorable for robust muscle regeneration.

Burnett’s keratin-based hydrogel, KeraGenics® Muscle, takes a different approach, providing a more favorable environment for cell infiltration and tissue repair.

Christ proposes to test each hydrogel with Larkin’s muscle units to assess their value in promoting integration with surrounding muscle and improving functional outcomes.

opens portrait of Professor Silvia Blemker

Silvia Blemker will use the massive data set collected as part of the AFIRM III award to build multi-scale models that connect volume, structure and material properties to force generation. Blemker is a professor of biomedical engineering and mechanical and aerospace engineering at UVA.

Building Muscle that Functions Like the Tissue it Replaces

Christ is not simply interested in developing a system for regenerating muscle tissue. His goal is to create one that functions and behaves like the tissue the system replaces.

For this, he is relying on the expertise of Silvia Blemker, a professor of biomedical engineering and mechanical and aerospace engineering at UVA and a specialist in finite element modeling of muscle tissue. Blemker will use the massive data set collected to build multi-scale models that connect volume, structure and material properties to force generation.

“The computer models make predictions that help design the most meaningful experiments to be performed in cell, tissue and animal model systems,” Blemker said. “The models also provide critical insight into the outcome of experiments, providing mechanistic information, which is exciting and beneficial.”

“Silvia’s work gives us the basis for improved understanding of the nature of the functional deficits associated with a muscle loss injury as well as the characteristics of regeneration needed to recover this function,” Christ said. “In other words, it gives us an objective standard for evaluating our results across multiple potential muscle injuries and many therapeutic solutions and possibilities.”

Christ will also be turning to another UVA colleague, Shawn Russell, an assistant professor of orthopedic surgery and mechanical and aerospace engineering at UVA. Russell will provide further insight about the impact of these treatments on gait and range of motion. Functional regeneration must not only improve the force of contraction but must also restore more natural movement.

"[Professor Silvia Blemker's work] gives us an objective standard for evaluating our results across multiple potential muscle injuries and many therapeutic solutions and possibilities."

George Christ, Professor of biomedical engineering and orthopedic surgery

Setting the Stage for the Challenges that Lie Ahead

In addition to the work on muscle, Christ’s team will examine the effectiveness of nerve repair technologies developed by Chief Scientist Simon Archibald and Senior Director of R&D Sunil Saini at Integra LifeSciences, a company that develops technology for surgical applications. The goal is to set the stage for the simultaneous nerve and muscle repair that is necessary for successfully treating volumetric muscle loss injuries.

Lastly, the award includes collaborators from the Department of Defense-funded Advanced Regenerative Manufacturing Institute. Chief Regulatory Officer Richard McFarland will provide guidance on regulatory issues, and Chief Technology Officer Thomas Bollenbach will provide advanced biomanufacturing expertise. The idea is to conduct research from the start with product development and commercialization in mind.

“My goal is to build completely native tissue, and to do so, I will need the best materials and the best people available at every step of the way,” Christ said. “That kind of multidisciplinary collaboration is something that UVA has always done well.”