Researchers Regenerate Skull Tissue Using Stem Cells and 3D Printed Scaffolding

Dentistry Today


Surgeons perform more than 5,000 cranioplasties each year on patients who have experienced critical size cranial defects resulting from congenital defects, head trauma, or tumor removals, according to the Herman Ostrow School of Dentistry at the University of Southern California (USC).

Traditional materials used to correct these deficits have been bone grafts from other human beings or the patients themselves or metal or plastic plates, none of which are ideal, the researchers said.

“Current solutions have quite a few drawbacks,” said Yang Chai, PhD, DDS, associate dean of research and one of the study’s authors. “So we saw this really unique need in the market for patients with large skull defects.”

Undesirable outcomes could include the patient’s body rejecting another person’s bone tissue, the surgeon not being able to harvest enough of the patient’s own bone tissue to cover the defect, or a titanium or a synthetic plate not growing along with a pediatric patient’s skull.

Now, the researchers are closer to developing a new regenerative therapy alternative, according to the school. Building upon prior work using a mouse model, the researchers fully healed critical size defects in swine using dental pulp neural crest mesenchymal stem cells and a 3D printed scaffold. 

The larger animal, swine, has a head size, skull thickness, and healing rate similar to human beings, bringing the therapeutic intervention close to actual patient care translation, the school said.

“Not only did we regenerate bone, but we have seen evidence that this newly generated bone is capable of the normal breakdown and buildup of bone cells over time, called bone turnover, which is not possible with current treatments,” said lead author and research lab specialist Zoe Johnson.

In the study, the regenerated bone formed a smooth, calvarial surface with both fully functional and aesthetically satisfying results, the researchers said.

The researchers now plan to file with the US Food and Drug Administration, which could either order further study or approve the project to go into phase I clinical trials.

If successful, the researchers said, the discovery could have major impacts on the quality of life for patients with critical size cranial defects.

“Craniofacial bones quite literally determine a person’s interface with the world. They protect vital organs that allow us to observe our environment and respond to it,” Johnson said.

The project is one of the latest from a multimillion-dollar research endeavor spearheaded by USC called the Center for Dental, Oral and Craniofacial Tissue and Organ Regeneration (C-DOCTOR).

C-DOCTOR is a consortium of California academic institutions whose mission is to become a sustainable, comprehensive national center that enables the clinical translation of innovative regenerative therapies to replace dental, oral, and craniofacial tissues or organs lost to congenital disorders, traumatic injuries, disease, and medical procedures.

“Regenerative medicine had always seemed like science fiction to me,” said Johnson. “Seeing results like ours, quality bone regenerated across an injury that would not have healed on its own, made fiction feel a little more like reality.”

“The driving force for our work is really about how we can improve patient care,” said Chai. “We want to be able to generate new approaches that will really reduce the pain and suffering for our patients. All of our effort, really, starts with the question, what can we do to make the patient care better for tomorrow?”

The study, “Mesenchymal Stem Cells and Three-Dimensional-Osteoconductive Scaffold Regenerate Calvarial Bone in Critical Size Defects in Swine,” was published by Stem Cells Translational Medicine.

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