Biomaterials Translational ›› 2024, Vol. 5 ›› Issue (4): 372-389.doi: 10.12336/biomatertransl.2024.04.004
• REVIEW • Previous Articles Next Articles
Jiawei Yang1, Nicholas G. Fischer2, Zhou Ye1,*()
Received:
2024-09-28
Revised:
2024-10-20
Accepted:
2024-11-01
Online:
2024-11-14
Published:
2024-12-28
Contact:
Zhou Ye, zhouye22@hku.hk.Yang, J.; Fischer, NG.; Ye, Z. Revolutionising oral organoids with artificial intelligence. Biomater Transl. 2024, 5(4), 372-389.
Figure 1. Schematic illustration of the development of oral organoids and perspectives of AI–enabled oral organoids. Created with BioRender.com. AI: artificial intelligence.
Figure 2. Various oral organoid applications. (A) Lingual mucosa organoid growth and histological analysis of the organoids. Staining for Ki67 showed that some cells actively proliferated in the outer periphery (arrows). Scale bars: 100 μm. Reprinted from Hisha et al.29 (B) Generation of a salivary gland organoid and immunofluorescence analysis of pan–cytokeratin (Pan–CK, red) and Sox9 (green). Scale bars: 300 μm. Reprinted from Tanaka et al.33 (C) Confocal images of a 3D culture system for murine dental epithelial organoids. Scale bars: 100 μm (top), 50 μm (bottom). Reprinted from Kim et al.45 (D) Schematic of suspension–culture method for taste bud organoids and the time–lapse imaging of suspension–cultured organoids under a bright–field microscope. Red squares indicate CVP and FOP. Scale bar: 50 μm. Reprinted from Adpaikar et al.48 Copyright 2024, Springer Nature. BMP4: bone morphogenetic protein 4; BMP–i: bone morphogenetic protein inhibitor; CVP: adult mice circumvallate papilla; DE: definitive ectoderm; E–cad: E–cadherin; EPI: epidermis; ES: embryonic stem cells; FGF: fibroblast growth factor; FOP: Foliate papillae; Foxc1: forkhead box C1; HE: haematoxylin eosin staining; Ki67: Kiel 67; Krt10: Keratin 10; ME: mesendoderm; NE: neural ectoderm; NJ: Noggin and Jagged1; NNE: non–neural ectoderm; OE: oral ectoderm; OE–SG: salivary gland placode; p63: tumour protein 63; P–cad: P–cadherin; Sox9: SRY–box transcription factor 9; TGFβ–i: transforming growth factor β inhibitor; TO–PRO–3: Thiazole red.
Figure 3. Applications of oral organoids as disease models. (A) Morphological and functional analyses of the human salivary–gland–derived organoids. The organoid has two layers of cells, an inner lining of epithelial (arrow in A4–2) and mucous cells (arrowhead in A4–2) and an outer lining of cells (open arrowhead in A4–2). These inner and outer layers are reminiscent of the luminal inner epithelial (arrow in A4–1) and mucous (arrowhead in A4–1) cells and outer myoepithelial cells (open arrowhead in A4–1), respectively, in the region of the intercalated duct connecting to the secretory end piece of the normal salivary gland. Scale bar: 200 μm (A1), 100 μm (A2), 50 μm (A3, A4). Reprinted from Yoshimoto et al.53 (B) H&E analysis and hTERT expression in normal oral and OSCC organoids. Reprinted from Yoon et al.55 hTERT: human telomerase reverse transcriptase; H&E: haematoxylin eosin staining; OSCC: oral squamous cell carcinoma.
Figure 4. Oral organoid applications for tooth and salivary gland formation. (A) Scheme of engineered tooth germ organoids fabrication for tooth regeneration. Reprinted from Wang and Sun.60 (B) Scheme of generation of engineered salivary gland organoids. Reprinted from Wang and Sun.60 3D: three–dimensional; BMP4: bone morphogenetic protein 4; FGF: fibroblast growth factor; Foc1: Fusarium oxysporum f. sp. cubense race 1; GelMA: gelatine methacrylate; HUVECs: human umbilical vein endothelial cells; iPSCs: induced pluripotent stem cells; PCL: polycaprolactone; PLGA: poly(lactic–co–glycolic acid); Sox1: SRY–box transcription factor 1.
Figure 5. Applications of advanced oral organoids. (A) SG organoid biofabrication workflow utilising two different magnetic 3D bioassembly platforms. Reprinted from Klangprapan et al.87 (B) Comparison of the sprouting ability of BMSCs and DPSCs, showcasing the potential of stem cells in forming vascularised organoids. *P < 0.05. Scale bars: 200 μm. Reprinted from Li et al.89 (C) Generation of assembled organoid comprising ECs, fibroblasts and cancer cells. ****P < 0.0001. Scale bars: 100 μm. Reprinted from Holkom et al.91 Copyright 2024, with permission from Wiley. 3D: three–dimensional; Au: gold; BMSCs: bone marrow–derived mesenchymal stem cells; CAF: cancer–associated fibroblast; CD31: cluster of differentiation 31; DAPI: blue–fluorescent DNA stain; DPSCs: dental pulp stem cells; EC: endothelial cells; FAO: fibroblast–attached organoid; Fe2O3: ferric oxide; hDPSC: human dental pulp stem cells; ns: not significant; OSCC: oral squamous cell carcinoma; Poly–L–Lys: polylysine; SG: salivary gland; TC: tumour cell.
Figure 6. Integration of AI organoid system in three steps: data construction, data preprocessing and model creation. Reprinted from Maramraju et al.108 AI: artificial intelligence.
Figure 7. AI–enabled organoids for early diagnosis and health monitoring. (A) MOrgAna workflow schematic: experimental design, segmentation and quantification. Reprinted from Gritti et al.123 (B) Brightfield versus Hoechst analysis of organoids. Reprinted from Deben et al.128 AI: artificial intelligence; BF: brightfield; MOrgAna: machine–learning based organoids analysis; OrBITS: organoid brightfield identification–based therapy screening.
Figure 8. AI–enabled organoids for disease prediction and drug screening. (A) Schematic flow of retinal differentiation experiments using a neural network to predict retinal differentiation. Reprinted from Kegeles et al.131 (B) Automated microfluidic 3D cellular and organoid culture platform for dynamical drug perturbations. Reprinted from Schuster et al.137 3D: three–dimensional; AI: artificial intelligence; mES: mouse embryonic stem cell; RxGFP: mES reporter cell line.
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