Tissue Engineering and Regenerative Medicine in Oral and Maxillofacial Surgery: The Most Important Clinical Applications of Mesenchymal Stem Cells

  • Marco TatulloEmail author
  • Massimo Marrelli
  • Francesco Paduano
  • Francesca Palmieri
  • Sandro Rengo
  • Carlo Rengo
  • Gianrico Spagnuolo
  • Bruna Codispoti


A growing number of patients require treatments in the field of oral and maxillofacial surgery, because of several different cues such as traumatic injuries, degenerative diseases, and cancer-related surgical treatments.

Since 1990, regenerative techniques were focused on the use of platelet concentrates and growth factors; in the following years, the development of new biomaterials introduced the era of tissue engineering, but the most fruitful advancement was represented by the introduction of mesenchymal stem cells (MSCs) that completely revolutionized tissue and organ regeneration.

This chapter aims to describe the most important advancements of regenerative technologies involved in oral and maxillofacial surgery, focusing on the wide application of MSCs and on the role of the newly discovered oral-derived MSCs in clinical uses.


Biomaterials Maxillofacial surgery Mesenchymal stem cells (MSCs) Regenerative medicine 


  1. 1.
    Murray JE, Merrill JP, Harrison JH. Renal homotransplantation in identical twins. 1955. J Am Soc Nephrol. 2001;12(1):201–4.PubMedGoogle Scholar
  2. 2.
    Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.CrossRefPubMedGoogle Scholar
  3. 3.
    Zomer HD, Vidane AS, Goncalves NN, Ambrosio CE. Mesenchymal and induced pluripotent stem cells: general insights and clinical perspectives. Stem Cells Cloning. 2015;8:125–34.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Till JE, Mc CE. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961;14:213–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968;6(2):230–47.PubMedCrossRefGoogle Scholar
  6. 6.
    Tatullo M, Marrelli M, Shakesheff KM, White LJ. Dental pulp stem cells: function, isolation and applications in regenerative medicine. J Tissue Eng Regen Med. 2015;9(11):1205–16.PubMedCrossRefGoogle Scholar
  7. 7.
    Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000;97(25):13625–30.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Reynolds AJ, Jahoda CA. Cultured human and rat tooth papilla cells induce hair follicle regeneration and fiber growth. Differentiation: Res Biol Div. 2004;72(9–10):566–75.CrossRefGoogle Scholar
  9. 9.
    Iohara K, Zheng L, Ito M, Tomokiyo A, Matsushita K, Nakashima M. Side population cells isolated from porcine dental pulp tissue with self-renewal and multipotency for dentinogenesis, chondrogenesis, adipogenesis, and neurogenesis. Stem Cells. 2006;24(11):2493–503.PubMedCrossRefGoogle Scholar
  10. 10.
    Ishkitiev N, Yaegaki K, Calenic B, Nakahara T, Ishikawa H, Mitiev V, et al. Deciduous and permanent dental pulp mesenchymal cells acquire hepatic morphologic and functional features in vitro. J Endod. 2010;36(3):469–74.PubMedCrossRefGoogle Scholar
  11. 11.
    Yang R, Chen M, Lee CH, Yoon R, Lal S, Mao JJ. Clones of ectopic stem cells in the regeneration of muscle defects in vivo. PLoS One. 2010;5(10):e13547.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A. 2003;100(10):5807–12.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet. 2004;364(9429):149–55.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Morsczeck C, Gotz W, Schierholz J, Zeilhofer F, Kuhn U, Mohl C, et al. Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol. 2005;24(2):155–65.PubMedCrossRefGoogle Scholar
  15. 15.
    Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One. 2006;1:e79.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Yang B, Qiu Y, Zhou N, Ouyang H, Ding J, Cheng B, et al. Application of stem cells in oral disease therapy: progresses and perspectives. Front Physiol. 2017;8:197.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Tomar GB, Srivastava RK, Gupta N, Barhanpurkar AP, Pote ST, Jhaveri HM, et al. Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine. Biochem Biophys Res Commun. 2010;393(3):377–83.PubMedCrossRefGoogle Scholar
  18. 18.
    Yi T, Lee S, Choi N, Shin HS, Kim J, Lim JY. Single cell clones purified from human parotid glands display features of multipotent epitheliomesenchymal stem cells. Sci Rep. 2016;6:36303.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Hutmacher DW, Sittinger M. Periosteal cells in bone tissue engineering. Tissue Eng. 2003;9(Suppl 1):S45–64.PubMedCrossRefGoogle Scholar
  20. 20.
    Marrelli M, Paduano F, Tatullo M. Cells isolated from human periapical cysts express mesenchymal stem cell-like properties. Int J Biol Sci. 2013;9(10):1070–8.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Tatullo M, Falisi G, Amantea M, Rastelli C, Paduano F, Marrelli M. Dental pulp stem cells and human periapical cyst mesenchymal stem cells in bone tissue regeneration: comparison of basal and osteogenic differentiated gene expression of a newly discovered mesenchymal stem cell lineage. J Biol Regul Homeost Agents. 2015;29(3):713–8.PubMedGoogle Scholar
  22. 22.
    Marrelli M, Paduano F, Tatullo M. Human periapical cyst-mesenchymal stem cells differentiate into neuronal cells. J Dent Res. 2015;94(6):843–52.PubMedCrossRefGoogle Scholar
  23. 23.
    Warnke PH, Wiltfang J, Springer I, Acil Y, Bolte H, Kosmahl M, et al. Man as living bioreactor: fate of an exogenously prepared customized tissue-engineered mandible. Biomaterials. 2006;27(17):3163–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Mesimaki K, Lindroos B, Tornwall J, Mauno J, Lindqvist C, Kontio R, et al. Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg. 2009;38(3):201–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Lendeckel S, Jodicke A, Christophis P, Heidinger K, Wolff J, Fraser JK, et al. Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. J Craniomaxillofac Surg. 2004;32(6):370–3.PubMedCrossRefGoogle Scholar
  26. 26.
    Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, Sato K, et al. Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J. 2010;16(2):169–75.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Yoshimura K, Sato K, Aoi N, Kurita M, Inoue K, Suga H, et al. Cell-assisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells. Dermatol Surg. 2008;34(9):1178–85.PubMedGoogle Scholar
  28. 28.
    Yoshikawa T, Mitsuno H, Nonaka I, Sen Y, Kawanishi K, Inada Y, et al. Wound therapy by marrow mesenchymal cell transplantation. Plast Reconstr Surg. 2008;121(3):860–77.PubMedCrossRefGoogle Scholar
  29. 29.
    Schmidt C. FDA approves first cell therapy for wrinkle-free visage. Nat Biotechnol. 2011;29(8):674–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Figueroa FE, Carrion F, Villanueva S, Khoury M. Mesenchymal stem cell treatment for autoimmune diseases: a critical review. Biol Res. 2012;45(3):269–77.PubMedCrossRefGoogle Scholar
  31. 31.
    Liotta F, Angeli R, Cosmi L, Fili L, Manuelli C, Frosali F, et al. Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing Notch signaling. Stem Cells. 2008;26(1):279–89.PubMedCrossRefGoogle Scholar
  32. 32.
    Volarevic V, Arsenijevic N, Lukic ML, Stojkovic M. Concise review: mesenchymal stem cell treatment of the complications of diabetes mellitus. Stem Cells. 2011;29(1):5–10.PubMedCrossRefGoogle Scholar
  33. 33.
    Williams AR, Trachtenberg B, Velazquez DL, McNiece I, Altman P, Rouy D, et al. Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling. Circ Res. 2011;108(7):792–6.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Stock P, Bruckner S, Ebensing S, Hempel M, Dollinger MM, Christ B. The generation of hepatocytes from mesenchymal stem cells and engraftment into murine liver. Nat Protoc. 2010;5(4):617–27.PubMedCrossRefGoogle Scholar
  35. 35.
    Morigi M, Imberti B, Zoja C, Corna D, Tomasoni S, Abbate M, et al. Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J Am Soc Nephrol. 2004;15(7):1794–804.PubMedCrossRefGoogle Scholar
  36. 36.
    Moller JF, Petersen JK. Efficacy of a fibrin sealant on healing of extraction wounds. Int J Oral Maxillofac Surg. 1988;17(2):142–4.PubMedCrossRefGoogle Scholar
  37. 37.
    Whitman DH, Berry RL, Green DM. Platelet gel: an autologous alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg. 1997;55(11):1294–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: Leucocyte activation: a new feature for platelet concentrates? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):e51–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Inchingolo F, Tatullo M, Marrelli M, Inchingolo AM, Inchingolo AD, Dipalma G, et al. Regenerative surgery performed with platelet-rich plasma used in sinus lift elevation before dental implant surgery: an useful aid in healing and regeneration of bone tissue. Eur Rev Med Pharmacol Sci. 2012;16(9):1222–6.PubMedGoogle Scholar
  40. 40.
    Marrelli M, Tatullo M. Influence of PRF in the healing of bone and gingival tissues. Clinical and histological evaluations. Eur Rev Med Pharmacol Sci. 2013;17(14):1958–62.PubMedGoogle Scholar
  41. 41.
    Inchingolo F, Ballini A, Cagiano R, Inchingolo AD, Serafini M, De Benedittis M, et al. Immediately loaded dental implants bioactivated with platelet-rich plasma (PRP) placed in maxillary and mandibular region. Clin Ter. 2015;166(3):e146–52.PubMedGoogle Scholar
  42. 42.
    Paduano F, Marrelli M, White LJ, Shakesheff KM, Tatullo M. Odontogenic differentiation of human dental pulp stem cells on hydrogel scaffolds derived from decellularized bone extracellular matrix and Collagen Type I. PLoS One. 2016;11(2):e0148225.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Paduano F, Marrelli M, Alom N, Amer M, White LJ, Shakesheff KM, et al. Decellularized bone extracellular matrix and human dental pulp stem cells as a construct for bone regeneration. J Biomater Sci Polym Ed. 2017;28(8):730–48.PubMedCrossRefGoogle Scholar
  44. 44.
    Marrelli M, Falisi G, Apicella A, Apicella D, Amantea M, Cielo A, et al. Behaviour of dental pulp stem cells on different types of innovative mesoporous and nanoporous silicon scaffolds with different functionalizations of the surfaces. J Biol Regul Homeost Agents. 2015;29(4):991–7.PubMedGoogle Scholar
  45. 45.
    Langer R, Vacanti JP. Tissue engineering. Science. 1993;260(5110):920–6.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Marco Tatullo
    • 1
    Email author
  • Massimo Marrelli
    • 2
  • Francesco Paduano
    • 2
  • Francesca Palmieri
    • 1
  • Sandro Rengo
    • 3
  • Carlo Rengo
    • 3
  • Gianrico Spagnuolo
    • 3
  • Bruna Codispoti
    • 1
  1. 1.Tecnologica Research Institute, Biomedical SectionCrotoneItaly
  2. 2.Marrelli Health, Clinical Research UnitCrotoneItaly
  3. 3.University of Naples “Federico II”NaplesItaly

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