In a breakthrough that could radically improve the care of people who suffer severe trauma to the face or skull, a team of scientists repaired a hole in a mouse’s skull by re-growing bone.

A joint team of the University of Chicago and Northwestern University researchers declared the results a resounding success. Using a powerful combination of technologies, they were able to regenerate the skull bone with supporting blood vessels in just the specific area where it was needed. The process worked more rapidly than previous methods and did not develop scar tissue.

Guillermo Ameer, professor of surgery at Feinberg School of Medicine and a professor of biomedical engineering at Northwestern’s McCormick School of Engineering, described the results as very exciting.

The research was published in the journal PLOS One and was supported by the National Institute of Dental and Craniofacial Research, the China Scholarship Council, the National Center for Advancing Translational Sciences and the Chicago Community Trust. The article’s corresponding author is Russell Reid, an associate professor of surgery at the University of Chicago Medical Center.

Reid and his long-time collaborator Dr. Tong-Chuan He, together with colleagues in Hyde Park brought the biological and surgical skills and knowledge to the table. Zari P. Dumanian, who is affiliated with the medical center’s surgery department, was the paper’s first author.

Ameer described the project as a true collaborative team effort in which Northwestern’s Regenerative Engineering Laboratory provided the biomaterials expertise.

Defects in, or Injuries to the skull or facial bones are very challenging to treat. The surgeon often needs to graft bone from the patient’s ribs, pelvis, or elsewhere, which is a painful procedure in itself. Complications increase if the area of injury is big, or if the graft needs to be contoured to the angle of the cranial curve or the jaw.

If all goes well with this new approach, painful bone grafting may well become obsolete.

The researchers conducted the experiment by harvesting skull cells from a mouse and engineering them to manufacture a potent protein to promote bone growth. They then used Ameer’s hydrogel to contain and deliver these cells to the affected area. The hydrogel acted like a temporary scaffolding. Ameer explained that the combination of all three technologies resulted in the results being so successful. Using skull cells or calvaria from the subject meant that the cells weren’t rejected by the body.

BMP proteins promote bone cell growth and BMP9 has been shown to do so more rapidly than other types.

BMP9 also appeared to improve the creation of blood vessels in the area. Ameer noted that being able to deliver skull cells that are capable of rapidly re-growing bone to the affected site safely promises a therapy that might be more surgeon friendly. Delivering them in vivo, as opposed to using them to grow bone in the laboratory, makes the process a lot faster. It also means that the process is not too complicated to scale up for patients.









The scaffolding hydrogel developed in Ameer’s laboratory, called PPCN-g, is a material based on citric acid. PPCN-g is a liquid that becomes a gel-like elastic material when it is warmed to body temperature. The liquid contains cells capable of producing bone and Ameer explained that when it is applied, it would conform to the shape of the bone defect to make a perfect fit. It then stays in place as a gel, localizing the cells to the site for the length of the repair. The PPCN-g is reabsorbed by the body as the bone regrows. The team found that these cells make natural looking bone in the presence of the PPCN-g. The new bone in that location is very similar to normal bone.

The three-part method was successful on a number of fronts.

The quality of the regenerated bone was better.

The bone growth was limited to the area defined by the scaffolding.

The old and new bone were continuous with no scar tissue.

The area healed very quickly.

The potential would be huge if the procedure can be adapted to treat people with aggressive cancers that have affected the face or skull, or those that have suffered trauma from car accidents. Surgeons will also be given a much sought after alternative option.

Ameer explained that the reconstruction procedure is a lot simpler when you can harvest a few cells, engineer them to produce the BMP9 protein, blend them in the PPCN-g solution, and then apply it to the bone defect site where you want it to kick-start the new bone growth process.

Although the technology is years away from being used in humans, proof of concept was demonstrated. Large faults in the skull that would normally not heal on their own could be healed using a protein, cells and a new hydrogel that come together in an entirely new way. The team is excited about the findings and their potential implications on the future of reconstructive surgery.