In vivo bioengineered tooth formation using decellularized tooth bud extracellular matrix scaffolds

The use of dental implants to replace lost or damaged teeth has become increasingly widespread due to their reported high survival and success rates. In reality, the long-term survival of dental implants remains a health concern, based on their short-term predicted survival of ~15 years, significant potential for jawbone resorption, and risk of peri-implantitis. The ability to create functional bioengineered teeth, composed of living tissues with properties similar to those of natural teeth, would be a significant improvement over currently used synthetic titanium implants. To address this possibility, our research has focused on creating biological tooth substitutes. The study presented here validates a potentially clinically relevant bioengineered tooth replacement therapy for eventual use in humans. We created bioengineered tooth buds by seeding decellularized tooth bud (dTB) extracellular matrix (ECM) scaffolds with human dental pulp cells, porcine tooth bud-derived dental epithelial cells, and human umbilical vein endothelial cells. The resulting bioengineered tooth bud constructs were implanted in the mandibles of adult Yucatan minipigs and grown for 2 or 4 months. We observed the formation of tooth-like tissues, including tooth-supporting periodontal ligament tissues, in cell-seeded dTB ECM constructs. This preclinical translational study validates this approach as a potential clinically relevant alternative to currently used dental implants.