The University of Iowa has been a long-standing world leader in caring for patients born with orofacial clefts and other disfiguring craniofacial abnormalities. These efforts were initially led by William Olin who pioneered clinical techniques for treating cleft lip and palate patients. Lina Moreno, associate professor and chair of the orthodontics, now spearheads the university's research and clinical efforts to care for these children. Kyungsup Shin, associate professor and graduate program director of orthodontics, is drawing from this rich history and expanding it with his own cleft palate research.
The National Institutes of Health (NIH) and the National Institute for Dental and Craniofacial Research (NIDCR) awarded Shin and his research team a $3.2M grant for their project developing a new reconstruction technique for orofacial cleft using biomimetic bone scaffolds and a real-time imaging platform in a rabbit model.
Cleft lip and/or palate is one of the most common craniofacial birth defects, affecting 1.25 out of 1000 live births. Those with this condition often have functional complications, such as difficulty speaking, swallowing, hearing, malocclusion, and aesthetic challenges. The condition often requires life-long management.
The current standard practice for treating cleft lip and palate is reconstruction of the affected areas by harvesting bone tissue from elsewhere in a patient’s body (autologous bone graft). This intervention prevents the patient’s body from immune rejection of the bone graft. Nevertheless, it involves invasive surgery to harvest the bone, which often involves surgical burden and risk of infection from where the bone was harvested. Additionally, it can be challenging to fit the graft precisely into the area and significant bone loss can result after the graft. Therefore, in many cases, this technique cannot successfully reconstruct the area in a way that addresses all the functional and aesthetic challenges each patient faces.
Shin and his team are addressing these problems by developing a novel delivery strategy for a patient’s own stem or progenitor cells along with a unique system for monitoring the success of the intervention. Since this technique uses a patient’s own stem or progenitor cells, if this new approach can be successfully translated to human patients in the future, it—like an autologous bone graft—will not be immunologically rejected by a patient. Furthermore, since bone is not harvested from the patient, there is no additional surgical burden, risk of infection at the site, or limitations on the amount of bone at the donor site available. This project is one step in a larger project to develop an alternative treatment for children who have cleft lip and palate.
“The main novelty of our project is to use personalized biomimetic scaffolds that are printed by a 3D printer so that they fit the unique dimensions of each patient’s affected area. If this new approach can be developed and translated to the clinical setting in the future, it will be another way of overcoming the limitations of the current clinical approaches,” Shin said.
The second novel aspect is his team’s use of a real-time near-infrared (NIR) fluorescence imaging platform to monitor bone regeneration and the degradation of the biomimetic scaffold. This monitoring system will help the team ensure the predictability of the intervention so that the treatment can address each patient's functional and aesthetic needs during the treatment. This project builds on Shin's previous work, which was supported by departmental start-up funds, the seed grant program at the College of Dentistry, and a series of research funds supported by the American Association of Orthodontists Foundation (AAOF).
“I am honored to be playing a small role in helping these patients and their families,” Shin said. “Parents and siblings are dedicated to caring for these children. Their efforts encourage all of us, clinicians and scientists, to work even harder to find better ways of caring for them.”
The project will be conducted by a collaborative, multi-institutional team involving Shin and Sang Jin Lee (associate professor at Wake Forest University) as principal investigators, and Xian Jin Xie, Doug Fredericks and Emily Peterson as co-investigators.