Key studies and technologies underpinning enamel and dentin regeneration for inlay therapy
| Study/Technology (Year) | Approach | Tissues targeted | Key findings/Significance |
|---|---|---|---|
| Nakao, 2007 [5] | Cell-based organ engineering | Enamel, dentin, pulp (whole tooth) | Combined epithelial + mesenchymal stem cells to form a tooth germ in vitro; upon implantation in mice, it grew a structurally correct tooth with enamel and dentin. Pioneering demonstration of whole-tooth regeneration. |
| Oshima, 2011 [6] | Organ germ method, transplantation | Whole tooth unit + bone | Grew a tooth bud in vitro then transplanted into a mouse jaw defect; the bioengineered tooth achieved bone integration and functional attachment. Proved that engineered tooth units can integrate into the oral environment. |
| Pandya, 2019 [4] | Review of strategies (physicochemical, biomimetic, cellular) | Enamel (and tooth tissues) | Outlined five pathways for enamel regeneration: (i) synthetic crystal growth, (ii) protein-guided mineralization, (iii) surface remineralization (e.g., peptides), (iv) cell-based engineering (hampered by lack of immortal ameloblast lines), (v) whole-tooth biological development. Emphasized the need for ameloblast sources and the challenges in recapitulating enamel’s structure. |
| Alghadeer, 2023 [7] | Stem cell differentiation and organoid formation | Enamel (with dentin precursors) | Differentiated human iPSCs into ameloblast-like cells and neural crest-like cells; formed enamel organoids secreting amelogenin, ameloblastin, enamelin and producing mineralized enamel matrix. Also identified odontoblast precursor cells. First successful creation of human enamel-forming organoids—milestone for enamel regeneration. |
| Han, 2021 [10] | Hybrid bioprinting (cell-laden hydrogel + polymer) | Dentin/Pulp (tooth structure) | Used a bio-ink with demineralized dentin matrix particles and DPSCs, printed in shape of a human molar with supportive PCL frame. After 15 days in odontogenic culture, the construct showed calcified deposits and upregulation of dentin markers (DSPP, DMP-1). Demonstrated feasibility of printing a living tooth scaffold and partial dentin regeneration in vitro. |
| Zhao, 2024 [1] | Schematic & review (Frontiers in Bioeng Biotech) | Multi-tissue (enamel, dentin, PDL, bone) | Described a digital process for dental tissue bioprinting: CT/scan to get 3D model, CAD design of scaffold including macro- and micro-structure, selection of suitable biomaterials and cells, then printing via extrusion, inkjet or laser methods. Highlighted current 3D printing applications in pulp, dentin, ligament, bone regeneration. Serves as a blueprint for integrating bioprinting with clinical workflows. |
| Sargod, 2010 [14] | Clinical case (9-year follow-up) | Enamel and dentin (natural fragment) | Reported a coronal tooth fracture repaired by bonding the original fragment with resin. After 9 years, the reattached fragment remained esthetic and functional. Illustrates that adhesive bonding to natural enamel/dentin is durable, supporting the concept that a natural tissue inlay can be securely cemented with existing adhesives. |
| Jablonski-Momeni, 2014 [9] | Self-assembling peptide applied clinically | Enamel (early caries lesions) | Although not a restoration, P11-4 peptide technology (Curodont™) induces mineralization in small enamel lesions, achieving lesion regression by regrowing hydroxyapatite in situ. Shows a current biomimetic tool for enamel repair in early-stage caries, foreshadowing more extensive regenerative treatments. |