# Alveolar ridge preservation with lyophilized microspheres of human dental pulp stem cells following 3D dynamic osteogenic induction

**Authors:** Yangyang Li, Jethro Zih-Shuo Wang, Zihan Yang, Fawen Wang, Haoyu Li, Chi Yang, Wenwen Yu, Zhiyuan Zhang

PMC · DOI: 10.1093/stcltm/szag015 · Stem Cells Translational Medicine · 2026-03-15

## TL;DR

This study explores using human dental pulp stem cells in a new way to improve alveolar ridge preservation after tooth extraction.

## Contribution

A novel bioactive material using lyophilized hDPSC microspheres preconditioned with 3D dynamic osteogenic induction is introduced.

## Key findings

- Lyophilized hDPSC microspheres showed enhanced alveolar bone preservation in preclinical models.
- The microspheres promoted superior new bone formation and improved bone microarchitecture.
- Results outperformed traditional artificial bone powder and control groups.

## Abstract

The clinical use of bone graft materials for alveolar ridge preservation following tooth extraction has become a standard procedure to facilitate subsequent implant restoration and prosthetic rehabilitation. However, the therapeutic efficacy of these materials is substantially limited by their bio-inertness, lack of cellular activity, and unpredictable resorption rates. The development of bioactive osteogenic materials capable of host integration and active promotion of bone regeneration would represent a significant advancement over current clinical protocols. To address this challenge, our research has focused on developing bioactive biomaterials using human dental pulp stem cells (hDPSCs). This study proposes a novel strategy for alveolar ridge repair utilizing lyophilized hDPSC microspheres preconditioned through a three-dimensional (3D) dynamic osteogenic induction system. We cultured hDPSCs into 3D microspheres and subjected them to osteogenic induction within our established dynamic culture system, followed by lyophilization to prepare “off-the-shelf” osteogenic tissues. The resulting lyophilized microsphere constructs were implanted into fresh extraction sockets of SD rats and New Zealand white rabbits and evaluated over 4 weeks. Comparative analysis demonstrated that the lyophilized microsphere group exhibited significantly enhanced alveolar bone preservation, superior new bone formation, and improved bone microarchitecture compared to both control groups and traditional artificial bone powder groups. This preclinical study validates the potential of lyophilized hDPSC microspheres as an efficient and clinically promising bioactive material for post–extraction alveolar ridge reconstruction.

Graphical Abstract

## Full-text entities

- **Genes:** THY1 (Thy-1 cell surface antigen) [NCBI Gene 7070] {aka CD90, CDw90}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, Eng (endoglin) [NCBI Gene 13805] {aka CD105, Endo, S-endoglin}, Thy1 (thymus cell antigen 1, theta) [NCBI Gene 21838] {aka CD90, T25, Thy-1, Thy-1.2, Thy1.1, Thy1.2}, RAP1A (RAP1A, member of RAS oncogene family) [NCBI Gene 5906] {aka C21KG, G-22K, KREV-1, KREV1, RAP1, SMGP21}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, SP7 (Sp7 transcription factor) [NCBI Gene 121340] {aka OI11, OI12, OSX, osterix}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Nt5e (5' nucleotidase, ecto) [NCBI Gene 23959] {aka 2210401F01Rik, 5'-NT, CD73, NT, Nt5, eNT}, CD34 (CD34 molecule) [NCBI Gene 947], BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, TGFB3 (transforming growth factor beta 3) [NCBI Gene 7043] {aka ARVD, ARVD1, LDS5, RNHF, TGF-beta3}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, TRAP [NCBI Gene 100187907], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Mcam (melanoma cell adhesion molecule) [NCBI Gene 84004] {aka 1-gicerin, CD146, CD149, Muc18, s-endo, s-gicerin}, MCAM (melanoma cell adhesion molecule) [NCBI Gene 4162] {aka CD146, HEMCAM, METCAM, MUC18, MelCAM}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, Cd34 (CD34 antigen) [NCBI Gene 12490], BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}
- **Diseases:** alveolar ridge defects (MESH:C565481), bone volume deficiency (MESH:D001847), depression (MESH:D003866), atrophy (MESH:D001284)
- **Chemicals:** PBS (MESH:D007854), IBMX (MESH:D015056), Alcian Blue (MESH:D000423), penicillin (MESH:D010406), H&amp;E (MESH:D006371), Th (MESH:D013910), paraffin (MESH:D010232), Oil Red O (MESH:C011049), indomethacin (MESH:D007213), saponin (MESH:D012503), Alizarin Red (MESH:C010078), Alizarin Red S (MESH:C004468), ascorbic acid (MESH:D001205), CO2 (MESH:D002245), alpha-MEM (MESH:C420642), Phalloidin (MESH:D010590), beta-glycerophosphate (MESH:C031463), BCA (-), Fast Red (MESH:C005215), Calcium (MESH:D002118), streptomycin (MESH:D013307), lipid (MESH:D008055), triglycerides (MESH:D014280), EDTA (MESH:D004492), TRIzol (MESH:C411644), dexamethasone (MESH:D003907), Sulfated glycosaminoglycans (MESH:C013786), DAPI (MESH:C007293), sodium citrate (MESH:D000077559), paraformaldehyde (MESH:C003043)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12989099/full.md

## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC12989099/full.md

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Source: https://tomesphere.com/paper/PMC12989099