Oral and Maxillofacial Surgery

Autologous tissue transplantation remains the gold standard for reconstructing tissue to restore oral and maxillofacial function and aesthetics. However, complications associated with tissue harvesting can be avoided using tissue-engineering approaches, which employ biocompatible cellular scaffolds combined with MSCs (mesenchymal stem/stromal cells) capable of differentiating toward the desired lineage.
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Periodontal Tissue Regeneration

Mesenchymal stem cells (MSCs) are being actively explored to regenerate periodontal tissues, soft tissues, and bone in oral and maxillofacial surgery. Periodontal tissues—including gingiva, periodontal ligament (PDL), cementum, and alveolar bone—require true functional regeneration, not just defect filling.

MSCs contribute via two main mechanisms: differentiation into osteoblasts, fibroblasts, and cementoblasts, and secretion of trophic factors and extracellular vesicles that modulate inflammation, stimulate angiogenesis, and recruit the patient’s own repair cells. Periodontal ligament, dental pulp, gingiva, and bone marrow–derived MSCs have demonstrated new bone, cementum, and PDL fiber formation in animal models, especially when combined with scaffolds such as collagen membranes or bone substitutes. Preclinical studies suggest that “site-specific” cells, such as PDL-derived MSCs, may achieve superior regeneration compared with bone marrow MSCs. Early clinical trials indicate improvements in clinical attachment level and probing depth, though sample sizes are still small and protocols vary.

Cell-free approaches using MSC-conditioned medium or exosomes are gaining interest, as they enhance bone fill and PDL regeneration while avoiding the challenges of cell harvesting and survival.

Soft Tissue Reconstruction

In soft tissue reconstruction, dental and gingival MSCs exhibit strong proliferative and angiogenic capabilities, supporting gingiva and oral mucosa healing and improving graft and implant integration.

Adipose-derived MSCs and buccal fat pad–derived cells are particularly useful for volume restoration and coverage. Their easy harvest and secretion of pro-angiogenic factors enhance vascularization and soft tissue quality around implants or in mucogingival surgery. Additionally, their immunomodulatory effects may stabilize chronic inflammatory conditions such as periodontitis or peri-implantitis, creating a favorable environment for long-term tissue stability.

Bone Renewal and Craniofacial Applications

For bone regeneration in the jaws, MSCs from bone marrow, dental pulp, PDL, periosteum, and buccal fat pad have been applied experimentally and clinically for:

  • Intrabony periodontal defects
  • Ridge defects
  • Sinus augmentation
  • Larger craniofacial defects

When seeded onto scaffolds—calcium phosphate ceramics, xenografts, or collagen matrices—MSCs support predictable bone formation with low donor site morbidity and good implant integration. Systematic reviews indicate that bone marrow and adipose-derived MSCs improve bone volume and density, while dental tissue–derived MSCs show particular promise for smaller intra-alveolar and periodontal defects.

Key Considerations and Future Directions

Across all applications, successful MSC therapy relies on:

  • Standardized, GMP-compliant cell preparation
  • Careful patient and defect selection
  • Use of well-designed scaffolds to support engraftment and regeneration

While current data are promising, larger and long-term clinical trials are needed before MSC-based therapies can become routine care in oral and maxillofacial surgery.

Therapeutic area:
Oral and Maxillofacial Surgery

REFERENCE:

Mustafa, K., Yamada, S., Sánchez, N., Mayol, M., Gjerde, C., & Sanz, M. (2025). Cell Therapy for Periodontal, Soft-Tissue, and Craniofacial Regeneration. Journal of periodontal research. https://doi.org/10.1111/jre.70011

Gao, P., Kajiya, M., Motoike, S., Ikeya, M., & Yang, J. (2024). Application of mesenchymal stem/stromal cells in periodontal regeneration: Opportunities and challenges. The Japanese Dental Science Review, 60, 95 - 108. https://doi.org/10.1016/j.jdsr.2024.01.001

Dipalma, G., Marinelli, G., Palumbo, I., Guglielmo, M., Riccaldo, L., Morolla, R., Inchingolo, F., Palermo, A., Inchingolo, A., & Inchingolo, A. (2025). Mesenchymal Stem Cells in Oral and Maxillofacial Surgery: A Systematic Review of Clinical Applications and Regenerative Outcomes. Journal of Clinical Medicine, 14. https://doi.org/10.3390/jcm14113623

Santos, N., Cotrim, K., Achôa, G., Kalil, E., Kantarci, A., & Bueno, D. (2024). The Use of Mesenchymal Stromal/Stem Cells (MSC) for Periodontal and Peri-implant Regeneration: Scoping Review. Brazilian Dental Journal, 35. https://doi.org/10.1590/0103-6440202406134

Chen, M., Huang, B., & Su, X. (2025). Mesenchymal stem cell–derived extracellular vesicles in periodontal bone repair. Journal of Molecular Medicine, 103, 137 - 156. https://doi.org/10.1007/s00109-025-02513-4

Ouchi, T., & Nakagawa, T. (2020). Mesenchymal stem cell-based tissue regeneration therapies for periodontitis. Regenerative Therapy, 14, 72 - 78. https://doi.org/10.1016/j.reth.2019.12.011

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Zhao, D., Yang, R., Wei, H., Yang, K., Yang, Y., Wang, N., Zhang, Q., Chen, F., & Zhang, T. (2025). Advances in the research of immunomodulatory mechanism of mesenchymal stromal/stem cells on periodontal tissue regeneration. Frontiers in Immunology, 15. https://doi.org/10.3389/fimmu.2024.1449411

Alarcón-Apablaza, J., Prieto, R., Rojas, M., & Fuentes, R. (2023). Potential of Oral Cavity Stem Cells for Bone Regeneration: A Scoping Review. Cells, 12. https://doi.org/10.3390/cells12101392

Khorasani, H., Sanchouli, M., Mehrani, J., & Sabour, D. (2021). Potential of Bone-Marrow-Derived Mesenchymal Stem Cells for Maxillofacial and Periodontal Regeneration: A Narrative Review. International Journal of Dentistry, 2021. https://doi.org/10.1155/2021/4759492

Lin, H., Chen, H., Zhao, X., Chen, Z., Zhang, P., Tian, Y., Wang, Y., Ding, T., Wang, L., & Shen, Y. (2021). Advances in mesenchymal stem cell conditioned medium-mediated periodontal tissue regeneration. Journal of Translational Medicine, 19. https://doi.org/10.1186/s12967-021-03125-5

Cai, S., Li, C., Wei, B., Ye, Z., Mao, Q., Ye, W., Rong, M., & Zeng, J. (2025). Current Perspectives on Mesenchymal Stem Cells as a Potential Treatment for Periodontal Diseases and Conditions. Genesis (New York, N.y. : 2000), 63. https://doi.org/10.1002/dvg.70024

Dipalma, G., Marinelli, G., Fiore, A., Balestriere, L., Carone, C., Buongiorno, S., Inchingolo, F., Minervini, G., Palermo, A., Inchingolo, A., & Inchingolo, A. (2025). The Evolving Role of Stem Cells in Oral Health and Regeneration: A Systematic Review. Surgeries. https://doi.org/10.3390/surgeries6030065

Zhou, L., Cai, W., Zhang, Y., Zhong, W., He, P., Ren, J., & Gao, X. (2025). Therapeutic effect of mesenchymal stem cell-derived exosome therapy for periodontal regeneration: a systematic review and meta-analysis of preclinical trials. Journal of Orthopaedic Surgery and Research, 20. https://doi.org/10.1186/s13018-024-05403-6

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Chew, J., Chuah, S., Teo, K., Zhang, S., Lai, R., Fu, J., Lim, L., Lim, S., & Toh, W. (2019). Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration. Acta biomaterialia, 89, 252-264. https://doi.org/10.1016/j.actbio.2019.03.021

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