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.
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).
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).
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.
Disclosure: Dr. Shi reports no conflict of interest.
Disclosure: Dr. Chai reports no conflict of interest.
Disclosure: Dr. Slavkin serves as a board member on the Board of Directors for the Patterson Companies.