Faculty published more than 200 research papers in leading journals in 20219 min read

Ann Arbor, Mich., Jan. 10, 2022 – With more than $23 million in annual research expenditures, the University of Michigan School of Dentistry generates a wide range of scientific research, from testing new biomaterials and exploring regenerative bone techniques to gaining new insight into how head-and-neck cancer cells resist chemotherapy.

Research led by faculty and staff is highlighted each year in leading scientific journals, helping to generate new knowledge in the oral health sciences and related fields that impacts people around the country and the world with improved health and outcomes.

“Our research mission is to promote an integration of basic, translational, clinical and health services research, along with associated educational programs, to stimulate discoveries and their implementation into practice,” said Vesa Kaartinen, Associate Dean for Research. “We want to encourage discoveries at every stage of their development into practice. This effort can be seen in the range, diversity and output of literature our faculty publish each year.”

In 2021, the school’s faculty published more than 200 papers, articles and reviews. Here are some of the top papers, based on high impact journal ratings, with links to their PubMed abstracts (with dental school faculty/staff noted in bold):

• Journal of Experimental Medicine: Squamous cell carcinoma subverts adjacent histologically normal epithelium to promote lateral invasion.  This paper documents the way cancer can subvert otherwise normal epithelium to promote invasion of small populations of tumor cells. This invasion of small tumor nests under adjacent histologically normal epithelium is associated with increased risk for recurrence and shorter remission of cancer.  This discovery was found to be consistent in both mouse models and human cells and it opens new possibilities for therapeutic strategies to reduce tumor recurrence.  Authors: Priyanka Singh, Rajat Banerjee, Songlin Piao, Marcell Costa de Medeiros, Emily Bellile, Min Liu, Dilna Damodaran Puthiya Veettil, Ligia Schmitd, Nickole Russo, Erika Danella, Ronald Inglehart,Kyriel M Pineault, Deneen Wellik, Greg Wolf, Nisha D’Silva.
• Biomaterials: Macropore design of tissue engineering scaffolds regulates mesenchymal stem cell differentiation fate.  This paper describes three-dimensional scaffold-based microenvironments toward the development of a tissue engineering-based treatment for craniosynostosis, a debilitating birth defect. It is characterized by the premature fusion of cranial bones resulting from loss of stem cells located in suture tissue between growing bones. The hypothesis is that scaffold pore size influences the regenerative fate of the cell-scaffold microenvironment towards stemness or differentiation, by modulating cell and tissue phenotype. The results indicate that provision of scaffolds containing regions of different pore sizes is a useful tissue engineering strategy to maintain stemness of cranial suture cells while also promoting cranial bone growth.  Authors:  W Benton Swanson, Maiko Omi, Zhen Zhang, Hwa Kyung Nam, Younghun Jung, Gefei Wang, Peter Ma, and Nan Hatch, Yuji Mishina.
• Advanced Healthcare Materials: A Highly Ordered, Nanostructured Fluorinated CaP-Coated Melt Electrowritten Scaffold for Periodontal Tissue Regeneration.  Focused on solutions for periodontitis, a chronic inflammatory, bacteria-triggered disorder affecting nearly half of American adults, this paper investigates how 3D printing techniques to build cell-based scaffolds can lead to periodontal regeneration. Highly ordered scaffolds engineered via Melt ElectroWriting (MEW) can be personalized to enable tissue-specific differentiation of progenitor cells. This guides simultaneous and coordinated regeneration of soft and hard periodontal tissues, while providing antimicrobial protection.  Authors: Arwa Daghrery, Jessica Ferreira, Isaac de Souza Araújo, Brian Clarkson, George Eckert, Sarit Bhaduri, Jos Malda, Marco Bottino.
• ACS Applied Materials Interfaces: Personalized and Defect-Specific Antibiotic-Laden Scaffolds for Periodontal Infection Ablation.  This paper looks at three designs of engineered tissue and which offers the best approach for predictable periodontal tissue growth and sustainability. One design led to increased new bone formation, lower bone loss, and reduced inflammatory response when compared to a control design. The results suggest that the fabrication of defect-specific antibiotic-laden scaffolds holds great potential toward the development of personalized (i.e. patient-specific medication) scaffolds to ablate infection while affording regenerative properties.  Authors:  Jessica Ferreira, Karla Kantorski, Nileshkumar Dubey, Arwa Daghrery, Christopher Fenno, Yuji Mishina, Hsun-Liang Chan, Gustavo Mendonça, Marco Bottino.
• Journal of Clinical Periodontology:  Maintenance visit regularity has a different impact on periodontitis-related tooth loss depending on patient staging and grading.  This paper documents an assessment of follow-up therapy visits by patients being treated for periodontitis and its correlation to tooth loss over time.  The regularity of maintenance visits, but not the overall quantity, had a significant impact on risk of tooth loss. Missing multiple years of maintenance had a larger influence on risk of tooth loss, but risk also increases based on other patient attributes (smoking, diabetes, etc.).  Authors:  Andrea Ravidà, Matthew Galli, Muhammad Saleh, Maria Vera Rodriguez, Musa Qazi, Giuseppe Troiano, Hsun-Liang Chan, Hom-Lay Wang.
• Cell Death and Disease:  The IL-6R and Bmi-1 axis controls self-renewal and chemoresistance of head and neck cancer stem cells.  Focused on head and neck cancer tumors, this paper hypothesizes a potential way to block the chemo resistance of cancer stem cells (CSCs). CSCs represent only 2-5 percent of total tumor cells yet contribute to tumor growth based on their innate resistance to chemo-, radio-, and immunotherapy. By using the monoclonal antibody drug Tocilizumab (designed for rheumatoid arthritis), there are positive results for reducing CSC’s intrinsic chemo resistance, which may suggest a viable strategy to reduce growth and recurrence of head and neck cancer tumors.   Authors:  Alexandra Herzog, Kristy Warner, Zhaocheng Zhang, Emily Bellile, Meera Bhagat, Rogerio Castilho, Greg Wolf, Peter Polverini, Alexander Pearson, Jacques Nör.
• Journal of Headache and Pain: Differential alteration of fMRI signal variability in the ascending trigeminal somatosensory and pain modulatory pathways in migraine.  This paper focuses on the interictal phase of migraine and its relationship with attack severity. Through the use of functional magnetic resonance imaging from migraine patients and healthy controls, the researchers acquired brain signals to compare blood oxygen levels and dynamic functional connectivity (dFC) in the time periods between migraine and its relationship with attack severity. The results indicate migraine is associated with alterations in temporal signal variability in certain channels of the brain, which may explain migraine-related pain and allodynia (pain from stimuli not normally painful). Contrasting patterns of time-varying connectivity within the thalmus, cortex and frontoparietal pathways could be linked to abnormal network integrity and instability for pain transmission and modulation.  Authors:  Manyoel Lim, Hassan Jassar, Dajung Kim, and Thiago Nascimento, Alex DaSilva.
• Journal of Periodontology:  Impact of mucosal phenotype on marginal bone levels around tissue level implants: A prospective controlled trial. This paper documents a clinical trial to compare clinical parameters and marginal bone levels (MBLs) around dental implants with a partially smooth collar between patients with thin (≤ 2 mm) and thick (> 2 mm) vertical mucosal phenotypes. After restoration, patients were reviewed and analyzed on a variety of measurements at different timepoints for one year. Results indicate that both thin and thick tissue phenotypes have similar outcomes at one year but more critical is the formation of the peri-implant supracrestal tissue height which plays a larger role in MBL than mucosal thickness in tissue level implant.Authors:  Carlos Garaicoa-Pazmino, Gustavo Mendonça, Alice Ou, Hsun-Liang Chan, James Mailoa, Fernando Suarez-Lopez Del Amo, Hom-Lay Wang.
• Cells: Pulpbow: A method to study the vasculogenic potential of mesenchymal stem cells from the dental pulp.  This paper looks at understanding how mesenchymal stem cells (MSCs) form blood vessels and the importance in creating mechanism-based approaches for the therapeutic use of these cells. An experimental model – the “pulpbow” (short for pulp and rainbow) – was developed. The multicolor tag is stable, permanent, unique to each cell and passed through generations. The pulpbow provides a way to understand how dental pulp stem cells contribute to blood vessel formation in 3D models for in vitro and ex vivo live cell tracking, and in vivo transplantation assays. The results reveal that the vasculogenesis process mediated by dental pulp stem cells is dynamic and the proximity to the sprouting area is critical for cell fate decisions.  Authors:  Andrea Mantesso, Zhaocheng Zhang, Kristy Warner, Alexandra Herzog, Ajai Pulianmackal, Jacques Nör.
• Journal of Dental Research: In Silico Modeling of Hyposalivation and Biofilm Dysbiosis in Root Caries.  The paper reviews the development of a computer model for root caries progression and how it is aggravated by hyposalivation. It can accelerate the conversion of a dental biofilm from having a symbiotic microbial relationship with the host (predominance of nonaciduric species) to a dysbiotic one (dominated by aciduric species). Using a mathematical model previously employed to investigate factors associated with biofilm dysbiosis, the researchers explored the deleterious effect of hyposalivation on the composition of the biofilm and the risk of root dentin demineralization. The results confirm the profound effect that prolonged sugar clearance has on the dynamics of dental biofilm composition and the subsequent risk of root caries.  Authors: D. Head, P.D. Marsh, D.A. Devine, Livia Tenuta.
• Journal of Dental Research: Role of Discoidin Domain Receptor 2 in Craniofacial Bone Regeneration.  This paper looks at the critical nature of an understudied collagen receptor, discoidin domain receptor 2 (Ddr2) and its role in skeletal development. Bone loss caused by trauma, neoplasia, congenital defects or periodontal disease is a major cause of disability and human suffering. Ddr2 loss-of-function mutations in humans and mice cause severe craniofacial and skeletal defects, but its role in craniofacial regeneration has not been examined. The researchers studied cranial defects generated in wild-type (WT) and Ddr2-deficient mice. The results indicated that Ddr2 is required for cranial bone regeneration and may be a novel target for therapy.  Authors:  Abdulaziz Binrayes, Chunxi Ge, and Fatma Mohamed, Renny Franceschi.

To highlight research by faculty and staff, the school holds an annual Research Day. This year’s event is on Thursday, Feb. 17, and will include research presentations, poster sessions and sponsor exhibits. More information on Research Day is available at the Research Office website here:  https://media.dent.umich.edu/sites/research-day/.

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The University of Michigan School of Dentistry is one of the nation’s leading dental schools engaged in oral health care education, research, patient care and community service.  General dental care clinics and specialty clinics providing advanced treatment enable the school to offer dental services and programs to patients throughout Michigan.  Classroom and clinic instruction prepare future dentists, dental specialists and dental hygienists for practice in private offices, hospitals, academia and public agencies.  Research seeks to discover and apply new knowledge that can help patients worldwide.  For more information about the School of Dentistry, visit us on the Web at: www.dent.umich.edu.  Contact: Lynn Monson, associate director of communications, at [email protected], or (734) 615-1971.