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HOUSTON, U.S.: Patients who suffer loss of mandibular bone because of cancer, infection, trauma or congenital disease are left with bony defects that are both esthetically and functionally challenging. Researchers from Rice University have developed a technique to generate engineered tissue customized to the specific defect: implanting a 3-D printed bioreactor against a rib. The stem cells and blood vessels from the rib grow a natural bone material that is tailored to the patient and can be transplanted to the mandible.
The goal of the research was to advance craniofacial reconstruction by taking advantage of the body’s natural healing powers. The technique has been developed to replace current reconstruction techniques that use autogenous bone graft tissue harvested from different areas, such as the lower leg, hip and shoulder.
“A major innovation of this work is leveraging a 3-D printed bioreactor to form bone grown in another part of the body while we prime the defect to accept the newly generated tissue,” said co-author Dr. Antonios Mikos, Louis Calder Professor of Bioengineering and Chemical and Biomolecular Engineering at the university.
The researchers made a rectangular defect in the mandibles of sheep. They created a template for 3-D printing and printed an implantable mold and a spacer, both made of PMMA, also known as bone cement. The goal of the spacer was to promote healing and prevent scar tissue from filling the defect site.
They removed enough bone from the animal model’s rib to expose the periosteum, which served as a source of stem cells and vasculature to seed scaffold material inside the mold. Test groups included crushed rib bone and synthetic calcium phosphate materials to make the biocompatible scaffold.
The mold, with the rib side open to create a tight interface, stayed in place for nine weeks before removal and transfer to the site of the defect, replacing the spacer. In the animal models, the new bone knitted to the old and soft tissue grew around and covered the site.
“We chose to use ribs because they’re easily accessed and a rich source of stem cells and vessels, which infiltrate the scaffold and grow into new bone tissue that matches the patient,” Mikos stated. “There’s no need for exogenous growth factors or cells that would complicate the regulatory approval process and translation to clinical applications.”
According to Mikos, using PMMA for the mold and spacer was a simple decision, as it has been regulated as a medical device for biological applications for decades. In World War II, when PMMA was used as a windshield for fighter planes, doctors noticed that shards embedded in injured pilots did not cause inflammation and thus considered it benign.
“We’re delighted to bring together this diversely talented team and deliver promising outcomes to the future healing of the wounded warrior and other patients in need of advanced treatments for the jaw and face,” Mikos said.
The study, titled “Biomaterials-aided mandibular reconstruction using in vivo bioreactors,” was published online in Proceedings of the National Academy of Sciences of the United States of America on March 18, 2019, ahead of inclusion in an issue.