Emerging Opportunities for the Next Generation of Dental Implants?

Science informs the clinical practice of dentistry! The pioneering scientific investigations of Bränemark and his team provided the intellectual scaffold upon which so much progress has been made in dental implants. For more than 50 years, scientific investigations have continued to define and improve upon the diagnosis, treatment planning, design and fabrication of materials and procedures, as well as outcome assessments. Millions of patients have benefited from this significant advance in dentistry. Quality of life improvements for edentulous patients has been nothing short of remarkable. Dental implants are heralded as a mechanical “solution” for biological applications. So, what is next? What might be the next generation of implants?
In tandem with the pioneering research by Bränemark and others around the world over the last 50 years, another very different type of scientific strategy has been advanced in which stem cells are identified, isolated, sometimes manipulated, and then utilized with a tissue engineering application—regeneration of bone, cartilage, skin, and possibly tooth roots. This alternative scientific strategy has been termed “biomimetics” meaning to mimic biological principles, processes, and/or structures—to design and fabricate cells, tissues, or organs as “biological solutions to biological problems.” Our colleague and co-author, Dr. Songtao Shi, at the University of Southern California (USC) School of Dentistry, has made one very exciting approach possible. Dr. Shi is a pediatric dentist with a PhD in Craniofacial Biology. His international scientific team has established “proof of principle” for a biomimetic approach to dental tooth root design and fabrication based upon biomimetics. Discovery is often the nexus where different and diverse lines of evidence converge!

 

Figure 1. Stem cell-mediated bio-root structure as an artificial crown support for the restoration of tooth function in swine. 1a. Stem cells from apical papilla (SCAP) isolated from swine were capable of forming a single colony cluster when plated at a low cell density. 1b. Swine periodontal ligament stem cells (PDLSCs) were capable of forming a single colony cluster. 1c. Extracted swine lower incisor and root-shaped hydroxyapatite carrier (HA) loaded with SCAP.


DR. SHI’S DISCOVERY

At the beginning of the 21st century, while working at the National Institute of Dental and Craniofacial Research (NIDCR), in Bethesda, Md, Dr. Shi curiously discovered that exfoliated deciduous human teeth from his own daughters actually contained functional mesenchymal stem cells.

Figure 1d. Gelfoam containing 10 x 106 PDLSCs (open arrow) was used to cover the HA/SCAP (black arrow) and implanted into the lower incisor socket (open triangle).
1e. HA/SCAP-Gelfoam/PDLSCs were implanted into a newly extracted incisor socket. A post channel was created inside the root shape HA carrier (arrow). 1f. The HA/SCAP-Gelfoam/PDLSC implant was sutured for 3 months.

Prior to that time, stem cells suitable to differentiate into white blood cells had been discovered and were introduced for the treatment of childhood leukemia in 1967. Further, mesenchymal stem cells were known to be located within bone marrow and techniques were available to harvest these unique cells to become bone, fibro-blasts, and cartilage. These prior advances informed Dr. Shi and enabled him to learn that these “stem” cells that he isolated from his daughter's deciduous teeth could be identified, isolated, grown in larger numbers, and then applied to various types of tissue engineering.
By definition and unique molecular regulatory controls, stem cells can divide and expand their numbers in a particular niche, and then can also be influenced or directed to organize and differentiate into specific types of cells and tissues such as dentin, dental pulp, cementum, and periodontal ligament. A few years ago, we (Drs. Chai and Slavkin) were successful in recruiting Dr. Shi from the NIDCR to the Center for Craniofacial Molecular Biology at the USC School of Dentistry where Dr. Shi actively continues his international scientific investigations through collaborations between Korean, Chinese, and American university scientists. Through a series of brilliant investigations, this international group led by Dr. Shi has successfully designed and fabricated tooth roots. These are roots that “grow” within the edentulous locations of the mandible or maxilla; and roots that form with viable periodontal ligaments, avoiding ankylosis and other confounding challenges of osseointegration.

Figure 1g. The HA/SCAP-Gelfoam/PDLSC implant (open arrow) was reexposed and the temporary post was removed to expose the post channel. 1h. A premade porcelain crown (arrow) was cemented to the bioroot/HA structure. 1i. The porcelain crown (arrow) exerts normal tooth function at 1-month post installation.

This discovery was made possible by the convergence of science and technology related to adult or postnatal stem cell biology, classical developmental biology of tooth formation (especially knowledge about periodontal ligament, cementum, and adjacent alveolar bone), and the opportunities emerging from biomimetics, tissue engineering, and transplantation studies. Financial support for these research studies through competitive peer-reviewed grants in part is derived from the NIDCR and the California Stem Cell Initiative (Figure 1).

CONCLUSION

So, when will biomimetic approaches become fully integrated into dental education and patient care? To date we know that the pioneering scientific studies of Dr. Marshall R. Urist that discovered “bone morphogenetic factor” in the mid-1960s, can be now celebrated with the further discoveries of the BMP gene families (1980s to 1990s) and their clinical applications for mandibular or maxillary bone ridge augmentation; and many other types of regeneration for intramembranous as well as endochondral bone defects. This example is given to highlight the fact that major changes in clinical practice take time, often many decades, and are further connected with professional cultures, “ways of knowing,” and “ways of doing.” It is our goal to advance the science that can best inform clinical dentistry towards the next generation of dental implants.


Dr. Shi received his DDS and MS of pediatric dentistry degrees from Peking University in 1983 and 1986, respectively. Following that Dr. Shi had served as a clinic assistant professor in the Department of Pediatric Dentistry at the same University for 2 and a half years. In 1994, he earned a PhD in craniofacial biology from the University of Southern California (USC). After the PhD training, Dr. Shi was honored to receive a 3 year NIH sponsored postdoctoral fellowship, which was designed to promote clinician involved in the research, at the University of California at San Francisco. After 1 year clinical practice as a private dentist in California, Dr. Shi joined NIDCR/NIH as clinical fellow and later became a tenure track Principal Investigator leading Dental Biology Section. He moved back to USC School of Dentistry in 2006 as an assistant professor and promoted as tenured associate professor in 2008. From 2000 to 2007, Dr. Shi and his collaborators have successfully isolated dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, and stem cells from apical papilla. Dr. Shi’s group has published their research in a variety of journals including PNAS, Nature Biotechnology, Lancet, Journal of Clinical Investigation, Nature Medicine PLoS ONE, JBMR, JDR, and Stem Cells. He can be reached via e-mail at songtaos@usc.edu.

Disclosure: Dr. Shi reports no conflict of interest.

Dr. Chai is the director of the Center for Craniofacial Molecular Biology, USC School of Dentistry. He holds an endowed chair position as the George and Mary Lou Boone Professor of Craniofacial Molecular Biology; serves as the chairman for the Division of Craniofacial Sciences and Therapeutics; and is a full professor at the USC School of Dentistry. He graduated from Peking University School of Stomatology and completed an extensive education and training in Oral and Maxicillofacial Surgery. He earned a PhD in Cranio-facial Biology, completed postdoctoral training at the Center for Craniofacial Molecular Biology, and then earned his DDS degree at USC School of Dentistry. Some of his interdisciplinary research interests include craniofacial birth defects and head and neck cancer. His research group has been working on the functional significance of TGF-beta signaling in regulating craniofacial development and the fate determination of cranial neural crest cells. His research team is supported by grants from the NIDCR, NIH; March of Dimes; American Cleft Palate Association; and the Zumberge award. He is also a regular member of the NIH SBDD Study Section. His research group publications appear in Developmental Cell, Development, Developmental Biology, and numerous other related scientific peer-reviewed journals. He participates on the editorial board of the journal Developmental Biology and Oral Disease and serves as a regular reviewer for several journals including Nature, Nature Medicine, Genes and Development, Developmental Cell, Development, Developmental Biology, Developmental Dynamics, IJDB, and JDR. He can be reached at (213) 740-0089 or via e-mail at ychai@usc.edu.

Disclosure: Dr. Chai reports no conflict of interest.

Dr. Slavkin is one of the world's leading authorities on craniofacial development and genetic birth defects. He earned his DDS degree from the USC School of Dentistry in 1965, and he was a practicing dentist while doing research as a postdoctoral Fellow at the UCLA School of Medicine and the USC department of biochemistry. In 1968, he joined the faculty of the USC School of Dentistry and began his career as an educator and scientist. He is the author of Developmental Craniofacial Biology (1979) and has edited 9 books, and published 260 peer-reviewed scientific papers. He led the first graduate program in craniofacial biology in the United States; was founding director of the Center for Craniofacial Molecular Biology; and the first holder of the George and Mary Lou Boone Chair in Craniofacial Molecular Biology. After he served as director of NIDCR, he returned in August 2000 to begin his tenure as dean of the USC School of Dentistry and G. Donald and Marian James Montgomery Dean’s Chair in Dentistry. He is a member of the Institute of Medicine of the National Academy of Sciences; a Fellow of the American Association for the Advancement of Science, and of both the American College of Dentists and the International College of Dentists; a member of the ADA, the International Association for Dental Research, and numerous other professional and scientific organizations. He holds honorary doctoral degrees from Georgetown University, the University of Paris, the University of Maryland, the University of Medicine and Dentistry of New Jersey, the University of Connecticut and the University of Montreal. He can be reached at (213) 740-0089 or via e-mail at slavkin@usc.edu.

Disclosure: Dr. Slavkin serves as a board member on the Board of Directors for the Patterson Companies.



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