Getting to the root of dental implant tissue engineering.

Regenerative medicine and tissue engineering technologies have greatly benefitted medicine and dentistry over the past years (Zaky & Cancedda 2009). The use of protein-, geneand stem cell-based therapeutics have been exploited significantly in the reconstruction of new tissues and organs (Discher et al. 2009). The field of oral and periodontal regenerative medicine has undergone significant recent advancements in areas such as total tooth engineering (Young et al. 2002) periodontal bioengineering (Seo et al. 2004) and oral implant osseointegration (Wikesjö et al. 2008). To date, a major ‘‘disconnect’’ exists between the principles of periodontal regeneration and oral implant osseointegration (see Fig. 1). That entity is the presence of a periodontal ligament (PDL) to allow for a more dynamic role beyond the functionally ankylosed or osseointegrated oral implant. In this month’s issue of the journal, Gault et al. (2010) demonstrate for the first time in humans, the tissue engineering of PDL and cementum-like structures on oral implants to promote the formation of implant–ligament biological interfaces or ligaplants capable of true, functional loading. This work is elegantly displayed in both pre-clinical and clinical experiments. Although the authors readily report that the findings are more of an early-stage, proof-of-concept, this work represents the potential that indeed tissue engineering approaches could become a reality in the formation of more functional implant fixtures in the future. The implementation of such an implant offers potential for titanium implant devices that can maintain form, function, and potential proprioceptive responses to allow for a tooth replacement more similar to a natural tooth (van Steenberghe 2000). Gault and colleagues paper has extended the work two decades ago when Buser et al. (1990) demonstrated that the placement of dental implants in proximity to tooth roots allowed for the migration, population and maturation of cementoblastic cells that formed a cementum-like tissue with an intervening PDL that could be verified through polarized light microscopy. The mechanism of this phenomenon appeared to be due to the migration of cementoblast and PDL fibroblast precursor cells due to the contact or proximity of the toothrelated cell populations to the oral implant. Over the years, numerous investigators have attempted to develop such implants similar to the ligaplants as shown by Gault and colleagues, but with varying degrees of success (Choi 2000, Kim et al. 2009). Of interest in the Gault investigation is that PDL fibroblasts could be harvested from hopeless teeth from mature individuals, aged 35–55 years. These PDL fibroblasts revealed the stem cell responsiveness to adhere, proliferate and differentiate into cells capable of forming cementum, ligament and bone along the alveolus originally destroyed by periodontitis. This finding supports numerous reports demonstrating the regenerative potential of PDL stem cells to differentiate into committed progenitor cells capable of forming multiple tissues (Fleischmannova et al. 2010). Of interest, is that the investigators utilized bioreactors to culture primary cultures and maintain the ‘‘stem-ness’’ of these cells over a 3week in vitro culture period before transplantation to the osseous defects. The cellular seeding methodology allowed for a spatial distribution of cells over the surfaces of the prototype implant devices to eventually form the ligamentous constructs. There is indeed a growing body of evidence demonstrating the significant potential of the formation of ligamentous attachments to teeth or other biomaterials. These approaches use cell, protein and gene therapy as well as rapid material prototyping methods to guide ligament neogenesis (Ishikawa et al. 2009, Lin et al. 2009, Park et al. 2010). These structure–functional interfaces are crucial in the biomechanical loading of biomaterials with cells anchored to the surface to initiate activities such as adhesion, migration and subsequent polarization for fibrous attachment (Moffat et al. 2008, Petrie et al. 2009). William V. Giannobile Department of Periodontics and Oral Medicine, Michigan Centre for Oral Health Research, School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, USA