NIDCR Grants Launch Tissue Regeneration Centers

Dentistry Today


The National Institute for Dental and Craniofacial Research (NIDCR) has awarded $2 million in grants to 10 research institutes and universities to establish tissue regeneration centers. These facilities will develop clinical applications in tissue engineering and regenerative medicine with dental, oral, and craniofacial tests.

“Tissue engineering studies mostly end up as basic papers published in scientific journals and rarely translate to clinical study in patients,” said Jeff Lotz, PhD, professor and vice chair of research in orthopedic surgery at the University of California, San Francisco (UCSF). The school is one of the 10 organizations receiving a grant.

NIDCR wanted to develop a new method to take what it considers to be mature technologies, ones that already have some evidence of efficacy, and then accelerate them to clinical trials,” Lotz said. “These resource centers are kind of that middle piece between developing the technology and actually putting it in patients.”

Tissue regeneration has significant potential for improving the outcomes of implant procedures. Inert implants, for example, may fail eventually. Active implants can more easily integrate with the body. Such technologies could be used to treat missing teeth, bone loss, clefts, oral mucosa, and just about any other tissue that would need healing.

“With bone grafts that are already vascularized, you don’t have to wait for the body to vascularize the graft on its own,” said Lotz. “This may reduce the morbidity of having to get a graft from the patient itself and moving that graft from a healthy area to the damaged area.”

The grants will be awarded in three stages. Stage 1, which will last for a year, will enable the recipients to develop a vision of their potential tissue regeneration center, along with a road map, organizational structure, and operational procedure for getting there. These awards will total about $150,000 each, or enough to assemble the interested parties.

Then, each recipient will have to compete for one of the stage 2 awards. Recipients will use these funds to identify and prioritize a clinical need as well as the interdisciplinary tissue regeneration teams that will be involved. These funds will be available for 3 to 4 years as the recipients move their concepts toward eventual product development.

“Stage 3 would award money to pay for the development of these technologies to clinical trials,” said Lotz. “It’s a multistep process, and during that process the plan is to winnow down the 10 centers to perhaps 2 or 3 nationally. There will be kind of a triage process as we move forward.”

Don’t expect cutthroat competition, though. The NIDCR anticipates plenty of collaboration between the recipients even as most of them are eliminated from consideration in future stages.

“If we’re going to go from 10 to 3 to 2, obviously if we can work together we might more likely get into stage 2 or stage 3,” said Lotz. “We’re in discussion with some of the other centers to identify whether there’s a good fit between the strengths and the gaps that we have versus others. I think it’s strategically a good idea to consider that.”

UCSF’s plans for the University of California Tissue Regeneration Center include work spread across 3 campuses. With its strong bioengineering program, the University of California at Davis will focus on developing existing and new animal models for preclinical testing. The University of California at Berkeley will use its expertise to develop biomaterials and the technologies that will characterize them.

“At UC San Francisco, our interest will be on the clinical side,” said Lotz. “We’ve got a very strong school of dentistry. Also, UCSF has a really great infrastructure for bringing novel technologies to a clinical practice. We have the Clinical & Translational Science Institute, which is specifically geared for this purpose.”

The University of Southern California (USC), another stage 1 recipient, will use its award to develop the Center for Dental, Oral and Craniofacial Tissue and Organ Regeneration (C-DOCTOR). Its researchers anticipate, for instance, developing 3-D printed dissolvable scaffolds that help organize stem cells for focused repair of damaged jawbones.

“Bone deficiency is a very common problem that patients face when they need an implant or when they have periodontal disease, traumatic injury, or a birth defect,” said Yang Chai, DDS, PhD, principal investigator of USC’s consortium. “Instead of stealing bone cells from other parts of the body, we’re going to be able to use stem cells to regenerate their own bone.”

“The nice thing about 3-D printing is you may be able to spatially integrate cells. You might be able to use materials with different physical properties,” said Lotz. “If you wanted graded tissue with bone on one end and cartilage on the other, you could pattern them outside the body and they’ll be more likely to produce the desired clinical result once they’re implanted.”

At the University of Michigan, the Michigan Regenerative Medicine Resource Center will include clinical teams that will work with technical advisory groups and data centers to assess what might be feasible clinically. It also will work with the Wyss Institute at Harvard University and the McGuire Institute in Houston.

“In recent years there have been major discoveries and advances in dentistry, medicine, biology, materials science, technology, and other fields,” said Dr. William Giannobile, leader of the Michigan Regenerative Medicine Resource Center. “NIDCR wants the Michigan Center and similar centers around the country to find ways to use those advances so clinicians can apply those discoveries to help their patients.”

Other grant recipients include Cedars-Sinai Medical Center; the Mayo Clinic; Tufts University; the University of California, Los Angeles; the University of Pennsylvania; the University of Pittsburgh; and the University of Virginia. These institutions don’t just have their eyes on the immediate grants, though. They also seek financial independence.

“We hope that these centers, and our center in particular, will become self-sustaining,” said Lotz. “As we verify clinical needs, recruit new technologies, and choose the best ones that match the clinical needs and bring them to clinical study, investors and industry who have an interest in commercialization will want to invest in their development.”

Success will lie in identifying the most pressing clinical need, however, and then assembling the right team across multiple disciplines. C-DOCTOR has enlisted representatives from endodontics, oral surgery, periodontics, and prosthodontics to suggest products based on cases they have seen in their own practices.

“The most significant part about this consortium is its emphasis on the translational aspects,” said Chai. “The NIDCR really wants us to build a product that can be used in patients.”

“These teams will be dedicated to selecting the most scientifically sound, clinically, and commercially applicable strategies to regenerate oral tissues,” said Dr. David Kohn, another leader with Michigan. “Our teams will take discoveries that show promise and provide the resources to advance the technologies to apply them more quickly than in the past.”

“A lot of times when scientists make a discovery that they think might have clinical value, they begin to develop that technology. Once they have this hammer, they look for nails,” said Lotz. “Our main goal is to identify where the need is the greatest and where adoption might be most well received.”

Another challenge lies in the preclinical studies, which cost money and are difficult to design, particularly if the researchers haven’t clarified what the clinical indication will be. Preclinical work needs to be driven by the clinical need and indication. And without good preclinical data showing that technology can work, it will fail.

“If we really can clarify the clinical need, what’s the value to the patient? And then we focus the technology development around those things that are more likely to end up with solutions that are going to be adopted because they have been shown to have value, shown to be cost effective,” said Lotz.

“The key goal of this center is to conduct those kinds of studies so that when we have a promising idea, we can check the boxes of all the required criteria that need to be met before we’re confident that a case study in patients is both safe and potentially effective,” Lotz said.

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