Organ Regeneration | Tooth Regeneration

Bioengineered tooth eruption and occlusion by bioengineered tooth germ transplantation

GFP-labeled bioengineered teeth erupted in the oral environment of adult mice

Tooth germ transplantation image

Tooth eruption image

We demonstrated that bioengineered tooth germ can successfully erupt at frequency of 80%, and can achieve functional occlusion with an opposing tooth in an adult oral environment, indicating that bioengineered teeth have the potential to recover the masticatory performance of a normal, natural tooth.
Etsuko Ikeda, Ritsuko Morita et al., Fully functional bioengineered tooth replacement as an organ replacement therapy. Proc. Natl. Acad. Sci. USA. 106, 13475-13480, 2009.

Figure: Eruption of a bioengineered tooth

(a) GFP-labeled bioengineered tooth erupted in the oral environment of adult mice.

(b) Eruption process of bioengineered tooth.

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Functional tooth regeneration by transplantation of bioengineered mature tooth

Toothunit Bright imageToothunit CT image
Toothunit tissue image
Tooth occlusion image
Organ replacement regenerative therapy is expected to achieve immediate function via the transplantation of a bioengineered mature organ. We demonstrate the successful transplantation of a bioengineered tooth unit, which is a model for a bioengineered mature organ, through bone integration into a missing tooth region.
Masamitsu Oshima et al., Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy. PLoS ONE, 6 (7) : e21531, 2011.

Figure: Transplantation of bioengineered tooth unit

(a) Generation of a bioengineered tooth unit

(b) Occlusal view of a bioengineered tooth unit after oral transplantation (green; bioengineered tooth unit)

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Engraftment of bioengineered tooth unit through the bone integration

Tooth unit tissue inmage

In the dental treatment, it has been expected to transplant of a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone into the tooth loss region through bone integration, which is connected between recipient bone and bioengineered alveolar bone in a bioengineered tooth unit.

Partial bone integration was observed at 14 days after transplantation, and full bone integration around a bioengineered tooth root was seen at 40 days after transplantation. Our current findings suggested that bioengineered teeth can be engrafted into regions of tooth loss through bone integration.

Figure: Engraftment of the bioengineered tooth unit

Histological analysis of the engrafted bioengineered tooth unit at 40 days post-transplantation.
NT, natural tooth; BT, bioengineered tooth;
AB, alveolar bone; PDL, periodontal ligament.

Bone regeneration using bioengineered tooth unit

Mondible CT image

Bone regeneration

Tooth loss causes a large amount of alveolar bone resorption and the loss of this bone is difficult to rectify with standard dental therapies such as dental implant and autologous tooth transplantation. The transplantation of a bioengineered tooth unit can regenerate not only the missing tooth but also the surrounding alveolar bone of the recipient.

Figure: Alveolar bone regeneration following the transplantation of a bioengineered tooth unit.

(a) Micro-CT images in adult murine natural mandible(left), and extensive bone defect model (right, arrowhead; bone defect)

(b) Three-dimensional superposition of micro-CT images of natural dentition (gray, double dotted line), a transplanted bioengineered tooth unit, and a no-transplantation control (left) at day 0 in an extensive bone defect (red, straight line), and at 45 days after transplantation (green, dotted line). The superior edges of the recipient alveolar bone are indicated by each line.

Functional tooth regeneration – Regeneration of periodontal tissue

Periodontal ligaments play essential roles in the pathogenic and physiologic responses of teeth to extreme mechanical forces from bone remodeling caused by orthodontic tooth movement. The periodontal ligaments of bioengineered teeth have been shown to reproduce successful, natural bone remodeling in response to mechanical stress, indicating that a bioengineered tooth can regenerate critical dental functions through the restoration and re-establishment of cooperation with the maxillofacial region.

Schematic representation of the tooth movement by the experimental orthodontic treatment.

Bone remodeling

Figure: Experimental tooth movement.

(a) Schematic representation of the tooth movement by the experimental orthodontic treatment.

(b) Sections of natural and bioengineered tooth were analyzed by TRAP staining and in situ hybridization of OCN at day 6 of the orthodontic treatment.

Functional tooth regeneration – Regeneration of the neural tissue

Perceptive potential of neurons entering the tissue of the bioengineered tooth.
The perception of noxious stimulation, such as mechanical stress and pain, are important for the protection and proper function of teeth.
We have provided evidence that nerve fibers innervating both the pulp and periodontal ligament (PDL) of a bioengineered tooth have the appropriate perceptive potential for nociceptive stimulation and can properly transduce these events to the central nervous system.

Figure:
Invasion of the nerve fiber in bioengineered tooth.

Nerve fibers are detected in the pulp / PDL in the bioengineered tooth.
D, dentin; P, dental pulp; AB, alveolar bone; PDL, periodontal ligament

Functional tooth regeneration – Regeneration of the neural tissue

We developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum.


 

Masamitsu Oshima, et al, Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy. Scientific reports, 4(6044), DOI:10.1038/srep06044, 2015.

Figure: Engraftment of a bio-hybrid implant

(a) Merged images of a bio-hybrid dental implant.

(b) Histological analysis of a natural tooth (upper), an engrafted osseo integrated implant (middle) and an engrafted bio-hybrid implant (lower). D, dentin; C, cementum; AB, alveolar bone; PDL, periodontal ligament; Imp, implant.

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