Third Teeth The evidence record
T3

Pulp and dentine repair (DPSC/SHED grafts, small molecules)

Multiple academic groups (Xuan et al. autologous pulp stem cell trial; Sharpe lab GSK-3 antagonist work) · repair · Small or narrow human data

Status

This is where human data actually is: a randomized, controlled trial of autologous pulp stem cell grafts in immature permanent incisors (26 patients evaluated, 24-month imaging) reported continued root development and regenerated pulp. Tideglusib dentine repair is preclinical; cell-free scaffolds and biomimetic enamel remineralization address surface lesions, not enamel regrowth. Clinically relevant regeneration, but categorically different from growing a whole tooth. A 2026 small randomized trial of platelet-rich fibrin versus mineral trioxide aggregate for direct pulp capping in 20 adult molars reports a borderline larger dentin-bridge volume with PRF at six months, with clinical outcomes indistinguishable from MTA. A 2026 histologic study of a human premolar extracted eight months after a regenerative endodontic procedure (Yang et al., single case, with the sound contralateral premolar as control) found dentin-like tissue lined by flattened DSPP-positive cells rather than an organized odontoblast layer, sparse and disorganized neurovascular ingrowth, and osteoid tissue in the apical region: radiographically closed and clinically quiet, but structurally not true pulp-dentin regeneration. This qualifies rather than strengthens the tier: the best human histology available shows repair-adjacent tissue, not a rebuilt pulp-dentin complex.

What would change this assessment

Controlled human evidence that repair extends beyond the pulp space , true enamel regrowth rather than surface remineralization.

Tier history

  • 2017-01-09 T2 Tideglusib (GSK-3 antagonist) promotes reparative dentine formation in a mouse tooth-injury model (Neves et al., Scientific Reports). Animal result.
  • 2018-08-22 T3 Randomized trial of autologous deciduous-tooth pulp stem cell implantation in immature permanent incisors: 26 patients evaluated with 24-month imaging, regenerated pulp tissue with vessels and nerves (Xuan et al., Sci Transl Med). Narrow endpoint , inside an existing tooth.

Sources on file

  1. Xuan K, Li B, Guo H, et al. (2018). Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Science Translational Medicine 10(455):eaaf3227. doi:10.1126/scitranslmed.aaf3227
  2. Neves VCM, Babb R, Chandrasekaran D, Sharpe PT (2017). Promotion of natural tooth repair by small molecule GSK3 antagonists. Scientific Reports 7:39654. doi:10.1038/srep39654
  3. Asthana G, Tamuli R, Manglani S, et al. (2026). Comparative Evaluation of Platelet-Rich Fibrin and Mineral Trioxide Aggregate in the Direct Pulp Capping of Carious Exposures: A Randomized Clinical Trial. Cureus 18(5):e108203. doi:10.7759/cureus.108203
  4. Yang F, Zhu X, Zhu X, Tan X, Wang J, Xie F (2026). Histologic Study of a Human Immature Permanent Premolar with Chronic Apical Periodontitis after Regenerative Endodontic Procedures. Journal of Endodontics 52(8):1359-1366. doi:10.1016/j.joen.2026.04.005

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