DFCs/TDM based artificial bio-root to obtain long-term functional root regeneration in non-human primate

Abstract

Stem cell/scaffold-based tissue engineering technology is expected to regenerate tooth root, thus replace dental implant. Although numerous patterns of biological tooth root have been constructed, most of them failed for the reasons involved the type of selected stem cells, scaffold materials, and the recombination strategy of cell-scaffold complexes. Here we introduced a novel functional biological root (FBR) with a sandwich structure, by which occlusal function and long-term masticatory function were gradually restored during two years functional evaluation in rhesus monkeys. FBR complex was constructed based on dental follicle cell sheets (DFCSs) and treated dentin matrix (TDM) under in vitro 3D suspension culture. Compared with other reported systems, DFCs displayed a more suitable seeding cell potential for bio-root construction due to the eminent odontogenic potential to develop cementum, periodontal ligament, and alveolar bone in vivo. Meanwhile, TDM also exhibited unique superiority of reserving native dentin tubules which can release numerous odontogenic proteins and factors comparing with other materials. Another unique characteristic of this work was that the favorable regeneration potential of FBR was proved in non-human primate, whose tooth morphology, number and development was more similar to humans, and the resulting FBRs closely resembled the natural tooth root in terms of their anatomical and physiological features, especially the “sandwich” structure of periodontal tissue, adequately demonstrating its potential application in tooth root regeneration.