Current Oral Health Reports

, Volume 5, Issue 4, pp 276–285 | Cite as

Growth Factors and Cell Homing in Dental Tissue Regeneration

  • Henry F. DuncanEmail author
  • Yoshifumi Kobayashi
  • Emi Shimizu
Dental Stem Cells in Tissue Regeneration (F Setzer, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Dental Stem Cells in Tissue Regeneration


Purpose of Review

To summarize current views on the role and therapeutic potential of growth factors (GFs) within endodontic cell homing.

Recent Findings

Cell homing/revitalization techniques aim to regenerate dentin and pulp using endogenous cells. Clinically, revitalization has successfully created new vital tissue in necrotic permanent teeth with an open apex; however, there is no evidence of new odontoblasts, pulp tissue, or predictable extension in root length. Although the response is reparative rather than regenerative, exciting opportunities to improve these biologically-based strategies remain by (1) efficiently sequestering dentin-matrix-components (DMCs) using irrigants and dental materials (2) designing next-generation GF-releasing scaffold materials and (3) utilizing other sources of GF such as cells and plasma-rich plasma and plasma-rich fibrin.


GFs can promote reparative-dentinogenesis and pulp-like tissue formation. The future development and clinical approval of GF-functionalized-scaffolds is a priority; however, current focus should be to harness DMCs and target the interaction of stem cells and GFs.


Cell homing Dental pulp stem cell Regenerative endodontics Dentin-pulp complex Growth factors Functionalized scaffolds 


Funding information

Work in Dr. Emi Shimizu’s lab is supported by a grant from the National Institutes of Dental and Craniofacial Research (NIDCR) R01-DE025885.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Reeves R, Stanley HR. The relationship of bacterial penetration and pulpal pathosis in carious teeth. Oral Surg Oral Med Oral Pathol. 1966;22:59–65.PubMedGoogle Scholar
  2. 2.
    Luder HU. Malformations of the tooth root in humans. Front Physiol. 2015;6:307.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Andreasen JO, Farik B, Munksgaard EC. Long-term calcium hydroxide as a root canal dressing may increase risk of root fracture. Dent Traumatol. 2002;18:134–7.PubMedGoogle Scholar
  4. 4.
    Caplan DJ, Cai J, Yin G, White BA. Root canal filled versus non-root canal filled teeth: a retrospective comparison of survival times. J Public Health Dent. 2005;65:90–6.PubMedGoogle Scholar
  5. 5.
    Simon S, Rilliard F, Berdal A, Machtou P. The use of mineral trioxide aggregate in one-visit apexification treatment: a prospective study. Int Endod J. 2007;40:186–97.PubMedGoogle Scholar
  6. 6.
    Jeeruphan T, Jantarat J, Yanpiset K, Suwannapan L, Khewsawai P, Hargreaves KM. Mahidol study 1: comparison of radiographic and survival outcomes of immature teeth treated with either regenerative endodontic or apexification methods: a retrospective study. J Endod. 2012;38:1330–6.PubMedGoogle Scholar
  7. 7.
    Alobaid AS, Cortes LM, Lo J, Nguyen TT, Albert J, Abu-Melha AS, et al. Radiographic and clinical outcomes of the treatment of immature permanent teeth by revascularization or apexification: a pilot retrospective cohort study. J Endod. 2014;40:1063–70.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Katebzadeh N, Dalton BC, Trope M. Strengthening immature teeth during and after apexification. J Endod. 1998;24:256–9.PubMedGoogle Scholar
  9. 9.
    • Wolters WJ, Duncan HF, Tomson PL, Karim IE, McKenna G, Dorri M, et al. Minimally invasive endodontics: a new diagnostic system for assessing pulpitis and subsequent treatment needs. Int Endod J. 2017;50:825–9 Highlighted problems with current classification of pulpitis and suggestive new classification. Linked new minimally invasive strategies to management. PubMedGoogle Scholar
  10. 10.
    Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: a review of current status and a call for action. J Endod. 2007;33:377–90.PubMedGoogle Scholar
  11. 11.
    •• Galler KM, Krastl G, Simon S, Van Gorp G, Meschi N, Vahedi B, et al. European Society of Endodontology position statement: revitalization procedures. Int Endod J. 2016;49:717–23 This position statement endorsed by the European Society of Endodontology (ESE) describes European views on revitalization. PubMedGoogle Scholar
  12. 12.
    Galler KM. Clinical procedures for revitalization: current knowledge and considerations. Int Endod J. 2016;49:926–36.PubMedGoogle Scholar
  13. 13.
    Nevins AJ, Finkelstein F, Borden BG, Laporta R. Revitalization of pulpless open apex teeth in rhesus monkeys, using collagen-calcium phosphate gel. J Endod. 1976;2:159–65.PubMedGoogle Scholar
  14. 14.
    Nevins A, Wrobel W, Valachovic R, Finkelstein F. Hard tissue induction into pulpless open-apex teeth using collagen-calcium phosphate gel. J Endod. 1977;3:431–3.PubMedGoogle Scholar
  15. 15.
    •• Shimizu E, Jong G, Partridge N, Rosenberg PA, Lin LM. Histologic observation of a human immature permanent tooth with irreversible pulpitis after revascularization/regeneration procedure. J Endod. 2012;38:1293–7 Demonstrated histologically that regeneration of pulp-like tissue possible in vivo in human teeth if the epithelial root sheath of Hertwig and the apical papilla are intact. PubMedGoogle Scholar
  16. 16.
    Peng C, Zhao Y, Wang W, Yang Y, Qin M, Ge L. Histologic findings of a human immature revascularized/regenerated tooth with symptomatic irreversible pulpitis. J Endod. 2017;43:905–9.PubMedGoogle Scholar
  17. 17.
    Goustin AS, Leof EB, Shipley GD, Moses HL. Growth factors and cancer. Cancer Res. 1986;46:1015–29.PubMedGoogle Scholar
  18. 18.
    Kim SG, Malek M, Sigurdsson A, Lin LM, Kahler B. Regenerative endodontics: a comprehensive review. Int Endod J. 2018. Scholar
  19. 19.
    Andreas K, Sittinger M, Ringe J. Toward in situ tissue engineering: chemokine-guided stem cell recruitment. Trends Biotechnol. 2014;32:483–92.PubMedGoogle Scholar
  20. 20.
    Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol. 2002;3:687–94.PubMedGoogle Scholar
  21. 21.
    Laterveer L, Lindley IJ, Hamilton MS, Willemze R, Fibbe WE. Interleukin-8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long-term myelolymphoid repopulating ability. Blood. 1995;85:2269–75.PubMedGoogle Scholar
  22. 22.
    Solanilla A, Grosset C, Duchez P, Legembre P, Pitard V, Dupouy M, et al. Flt3-ligand induces adhesion of haematopoietic progenitor cells via a very late antigen (VLA)-4- and VLA-5-dependent mechanism. Br J Haematol. 2003;120:782–6.PubMedGoogle Scholar
  23. 23.
    Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Ex Med. 1997;185:111–20.Google Scholar
  24. 24.
    Hattori K, Heissig B, Rafii S. The regulation of hematopoietic stem cell and progenitor mobilization by chemokine SDF-1. Leuk Lymphoma. 2003;44:575–82.PubMedGoogle Scholar
  25. 25.
    Rafii S, Heissig B, Hattori K. Efficient mobilization and recruitment of marrow-derived endothelial and hematopoietic stem cells by adenoviral vectors expressing angiogenic factors. Gene Ther. 2002;9:631–41.PubMedGoogle Scholar
  26. 26.
    Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004;118:149–61.PubMedGoogle Scholar
  27. 27.
    Wang J, Mukaida N, Zhang Y, Ito T, Nakao S, Matsushima K. Enhanced mobilization of hematopoietic progenitor cells by mouse MIP-2 and granulocyte colony-stimulating factor in mice. J Leukoc Biol. 1997;62:503–9.PubMedGoogle Scholar
  28. 28.
    •• Smith AJ, Duncan HF, Diogenes A, Simon S, Cooper PR. Exploiting the bioactive properties of the dentin-pulp complex in regenerative endodontics. J Endod. 2016;42:47–56 State of the art review highlighting the role of dentin matrix components to contribute GFs and other bioactive factors to pulp repair and regeneration. PubMedGoogle Scholar
  29. 29.
    Zhang J, Lu X, Feng G, Gu Z, Sun Y, Bao G, et al. Chitosan scaffolds induce human dental pulp stem cells to neural differentiation: potential roles for spinal cord injury therapy. Cell Tissue Res. 2016;366:129–42.PubMedGoogle Scholar
  30. 30.
    Bezgin T, Yilmaz AD, Celik BN, Kolsuz ME, Sonmez H. Efficacy of platelet-rich plasma as a scaffold in regenerative endodontic treatment. J Endod. 2015;41:36–44.PubMedGoogle Scholar
  31. 31.
    Piva E, Silva AF, Nör JE. Functionalized scaffolds to control dental pulp stem cell fate. J Endod. 2014;40:S33–40.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Bottino MC, Pankajakshan D, Nör JE. Advanced scaffolds for dental pulp and periodontal regeneration. Dent Clin N Am. 2017;61:689–711.PubMedGoogle Scholar
  33. 33.
    Duncan HF, Smith AJ, Fleming GJ, Reid C, Smith G, Cooper PR. Release of bio-active dentine extracellular matrix components by histone deacetylase inhibitors (HDACi). Int Endod J. 2017;50:24–38.PubMedGoogle Scholar
  34. 34.
    Kim SG, Zhou J, Solomon C, Zheng Y, Suzuki T, Chen M, et al. Effects of growth factors on dental stem/progenitor cells. Dent Clin N Am. 2012;56:563–75.PubMedGoogle Scholar
  35. 35.
    Eramo S, Natali A, Pinna R, Milia E. Dental pulp regeneration via cell homing. Int Endod J. 2018;51:405–19.PubMedGoogle Scholar
  36. 36.
    Kim SG, Zheng Y, Zhou J, Chen M, Embree MC, Song K, et al. Dentin and dental pulp regeneration by the patient’s endogenous cells. Endod Topics. 2013;28:106–17.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Kim JY, Xin X, Moioli EK, Chung J, Lee CH, Chen M, et al. Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing. Tissue Eng Part A. 2010;16:3023–31.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol? J Endod. 2004;30:196–200.PubMedGoogle Scholar
  39. 39.
    •• Shimizu E, Ricucci D, Albert J, Alobaid AS, Gibbs JL, Huang GT, et al. Clinical, radiographic, and histological observation of a human immature permanent tooth with chronic apical abscess after revitalization treatment. J Endod. 2013;39:1078–83 Demonstrated that although successful clinically, histologically there no pulp tissue, only bone-like fibrous connective tissue in case of pulp necrosis. PubMedGoogle Scholar
  40. 40.
    Graham L, Cooper PR, Cassidy N, Nor JE, Sloan AJ, Smith AJ. The effect of calcium hydroxide on solubilisation of bio-active dentine matrix components. Biomaterials. 2006;27:2865–73.PubMedGoogle Scholar
  41. 41.
    Tomson PL, Grover LM, Lumley PJ, Sloan AJ, Smith AJ, Cooper PR. Dissolution of bio-active dentine matrix components by mineral trioxide aggregate. J Dent. 2007;35:636–42.PubMedGoogle Scholar
  42. 42.
    Galler KM, Widbiller M, Buchalla W, Eidt A, Hiller KA, Hoffer PC, et al. EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells. Int Endod J. 2016;49:581–90.PubMedGoogle Scholar
  43. 43.
    Alghilan MA, Windsor LJ, Palasuk J, Yassen GH. Attachment and proliferation of dental pulp stem cells on dentine treated with different regenerative endodontic protocols. Int Endod J. 2017;50:667–75.PubMedGoogle Scholar
  44. 44.
    Niu Y, Li Q, Ding Y, Dong L, Wang C. Engineered delivery strategies for enhanced control of growth factor activities in wound healing. Adv Drug Deliv Rev. 2018.
  45. 45.
    Fischbach GD, Fischbach RL. Stem cells: science, policy, and ethics. J Clin Invest. 2004;114:1364–70.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Mason C, Dunnill P. A brief definition of regenerative medicine. Regen Med. 2008;3:1–5.PubMedGoogle Scholar
  47. 47.
    Bojic S, Volarevic V, Ljujic B, Stojkovic M. Dental stem cells-characteristics and potential. Histol Histopathol. 2014;29:699–706.PubMedGoogle Scholar
  48. 48.
    Fayazi S, Takimoto K, Diogenes A. Comparative evaluation of chemotactic factor effect on migration and differentiation of stem cells of the apical papilla. J Endod. 2017;43:1288–93.PubMedGoogle Scholar
  49. 49.
    Jeanneau C, Lundy FT, El Karim IA, About I. 47. Potential therapeutic strategy of targeting pulp fibroblasts in dentin-pulp regeneration. J Endod 2017:43:S17–S24.PubMedGoogle Scholar
  50. 50.
    Saito K, Oshima H. Differentiation capacity and maintenance of dental pulp stem/progenitor cells in the process of pulpal healing following tooth injuries. Journal J Oral Biosci. 2017;59:63–70.Google Scholar
  51. 51.
    Cooper PR, Takahashi Y, Graham LW, Simon S, Imazato S, Smith AJ. Inflammation-regeneration interplay in the dentine-pulp complex. J Dent. 2010;38:687–97.PubMedGoogle Scholar
  52. 52.
    Alongi DJ, Yamaza T, Song Y, Fouad AF, Romberg EE, Shi S, et al. Stem/progenitor cells from inflamed human dental pulp retain tissue regeneration potential. Regen Med. 2010;5:617–31.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Suzuki T, Lee CH, Chen M, Zhao W, Fu SY, Qi JJ, et al. Induced migration of dental pulp stem cells for in vivo pulp regeneration. J Dent Res. 2011;90:1013–8.PubMedGoogle Scholar
  54. 54.
    Yang JW, Zhang YF, Wan CY, Sun ZY, Nie S, Jian SJ, et al. Autophagy in SDF-1alpha-mediated DPSC migration and pulp regeneration. Biomaterials. 2015;44:11–23.PubMedGoogle Scholar
  55. 55.
    Gervois P, Wolfs E, Dillen Y, Hilkens P, Ratajczak J, Driesen RB, et al. Paracrine maturation and migration of SH-SY5Y cells by dental pulp stem cells. J Dent Res. 2017;96:654–62.PubMedGoogle Scholar
  56. 56.
    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.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Sonoyama W, Liu Y, Yamaza T, Tuan RS, Wang S, Shi S, et al. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod. 2008;34:166–71.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Galler KM, Eidt A, Schmalz G. Cell-free approaches for dental pulp tissue engineering. J Endod. 2014;40:S41–5.PubMedGoogle Scholar
  59. 59.
    Chrepa V, Pitcher B, Henry MA, Diogenes A. Survival of the apical papilla and its resident stem cells in a case of advanced pulpal necrosis and apical periodontitis. J Endod. 2017;43:561–7.PubMedGoogle Scholar
  60. 60.
    Huang GT. Pulp and dentin tissue engineering and regeneration: current progress. Regen Med. 2009;4:697–707.PubMedPubMedCentralGoogle Scholar
  61. 61.
    de Almeida JF, Chen P, Henry MA, Diogenes A. Stem cells of the apical papilla regulate trigeminal neurite outgrowth and targeting through a BDNF-dependent mechanism. Tissue Eng Part A. 2014;20:3089–100.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Isaka J, Ohazama A, Kobayashi M, Nagashima C, Takiguchi T, Kawasaki H, et al. Participation of periodontal ligament cells with regeneration of alveolar bone. J Periodontol. 2001;72:314–23.PubMedGoogle Scholar
  63. 63.
    Huang GT, Gronthos S, Shi S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res. 2009;88:792–806.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Abdallah BM, Kassem M. New factors controlling the balance between osteoblastogenesis and adipogenesis. Bone. 2012;50:540–5.PubMedGoogle Scholar
  65. 65.
    Ruangsawasdi N, Zehnder M, Patcas R, Ghayor C, Siegenthaler B, Gjoksi B, et al. Effects of stem cell factor on cell homing during functional pulp regeneration in human immature teeth. Tissue Eng Part A. 2017;23:115–23.PubMedGoogle Scholar
  66. 66.
    Hattori K, Dias S, Heissig B, Hackett NR, Lyden D, Tateno M, et al. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med. 2001;193:1005–14.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Tamma R, Ribatti D. Bone niches, hematopoietic stem cells, and vessel formation. Int J Mol Sci. 2017;18.PubMedCentralGoogle Scholar
  68. 68.
    Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999;18:3964–72.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Cassidy N, Fahey M, Prime SS, Smith AJ. Comparative analysis of transforming growth factor-β isoforms 1-3 in human and rabbit dentine matrices. Arch Oral Biol. 1997;42:219–23.PubMedGoogle Scholar
  70. 70.
    Smith AJ. Vitality of the dentin-pulp complex in health and disease: growth factors as key mediators. J Dent Educ. 2003;67:678–89.PubMedGoogle Scholar
  71. 71.
    Mazzoni A, Tjäderhane L, Checchi V, Di Lenarda R, Salo T, Tay FR, et al. Role of dentin MMPs in caries progression and bond stability. J Dent Res. 2015;94:241–51.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Dung SZ, Gregory RL, Li Y, Stookey GK. Effect of lactic acid and proteolytic enzymes on the release of organic matrix components from human root dentin. Caries Res. 1995;29:483–9.PubMedGoogle Scholar
  73. 73.
    Charadram H, Farahani RM, Harty D, Rathsam C, Swain MV, Hunter N. Regulation of reactionary dentin formation by odontoblasts in response to polymicrobial invasion of dentin matrix. Bone. 2012;2012(50):265–75.Google Scholar
  74. 74.
    Smith AJ, Tobias RS, Cassidy N, Plant CG, Browne RM, Begue-Kirn C, et al. Odontoblast stimulation in ferrets by dentine matrix components. Arch Oral Biol. 1994;39:13–22.PubMedGoogle Scholar
  75. 75.
    Ferracane JL, Cooper PR, Smith AJ. Dentin matrix component solubilization by solutions of pH relevant to self-etching dental adhesives. J Adhes Dent. 2013;15:407–12.PubMedGoogle Scholar
  76. 76.
    Widbiller M, Eidt A, Hiller KA, Buchalla W, Schmalz G, Galler KM. Ultrasonic activation of irrigants increases growth factor release from human dentine. Clin Oral Investig. 2017;21:879–88.PubMedGoogle Scholar
  77. 77.
    Galler KM, Buchalla W, Hiller KA, Federlin M, Eidt A, Schiefersteiner M, et al. Influence of root canal disinfectants on growth factor release from dentin. J Endod. 2015;41:363–8.PubMedGoogle Scholar
  78. 78.
    • Martin DE, De Almeida JF, Henry MA, Khaing ZZ, Schmidt CE, Teixeira FB, et al. Concentration-dependent effect of sodium hypochlorite on stem cells of apical papilla survival and differentiation. J Endod. 2014;40:51–5 Ex vivo study highlighting the effects of increasing sodium hypochlorite concentration on the biological response of SCAP.PubMedGoogle Scholar
  79. 79.
    Shrestha S, Torneck CD, Kishen A. Dentin conditioning with bioactive molecule releasing nanoparticle system enhances adherence, viability, and differentiation of stem cells from apical papilla. J Endod. 2016;42:717–23.PubMedGoogle Scholar
  80. 80.
    Bègue-Kirn C, Smith AJ, Ruch JV, Wozney JM, Purchio A, Hartmann D, et al. Effects of dentin proteins, transforming growth factor beta 1 (TGF beta 1) and bone morphogenetic protein 2 (BMP2) on the differentiation of odontoblast in vitro. Int J Dev Biol. 1992;36:491–503.PubMedGoogle Scholar
  81. 81.
    Bento LW, Zhang Z, Imai A, Nör F, Dong Z, Shi S, et al. Endothelial differentiation of SHED requires MEK1/ERK signaling. J Dent Res. 2013;92:51–7.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Yoshiba N, Edanami N, Tohma A, Takeuchi R, Ohkura N, Hosoya A, et al. Detection of bone marrow-derived fibrocytes in human dental pulp repair. Int Endod J. 2018. Scholar
  83. 83.
    • Lambrichts I, Driesen RB, Dillen Y, Gervois P, Ratajczak J, Vangansewinkel T, et al. Dental pulp stem cells: their potential in reinnervation and angiogenesis by using scaffolds. J Endod. 2017;43:S12–6 Comprehensive review highlighting the role of DPSCs and GFs in angiogenesis and neurogenesis. PubMedGoogle Scholar
  84. 84.
    Aranha AM, Zhang Z, Neiva KG, Costa CA, Hebling J, Nör JE. Hypoxia enhances the angiogenic potential of human dental pulp cells. J Endod. 2010;36:1633–7.PubMedGoogle Scholar
  85. 85.
    Albanese MEL, Polizzi B, Campisi G. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration. Immun Ageing. 2013;10:23.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Roselló-Camps À, Monje A, Lin GH, Khoshkam V, Chávez-Gatty M, Wang HL, et al. Platelet-rich plasma for periodontal regeneration in the treatment of intrabony defects: a meta-analysis on prospective clinical trials. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120:562–74.PubMedGoogle Scholar
  87. 87.
    Rodriguez IA, Growney Kalaf EA, Bowlin GL, Sell SA. Platelet-rich plasma in bone regeneration: engineering the delivery for improved clinical efficacy. Biomed Res Int. 2014;392398.Google Scholar
  88. 88.
    Volpi P, Quaglia A, Schoenhuber H, Melegati G, Corsi MM, Banfi G, et al. Growth factors in the management of sport-induced tendinopathies: results after 24 months from treatment. A pilot study. J Sports Med Phys Fitness. 2010;50:494–500.PubMedGoogle Scholar
  89. 89.
    Lyras DN, Kazakos K, Georgiadis G, Mazis G, Middleton R, Richards S, et al. Does a single application of PRP alter the expression of IGF-I in the early phase of tendon healing? J Foot Ankle Surg. 2011;50:276–82.PubMedGoogle Scholar
  90. 90.
    Alsousou J, Ali A, Willett K, Harrison P. The role of platelet-rich plasma in tissue regeneration. Platelets. 2013;24:173–82.PubMedGoogle Scholar
  91. 91.
    Jadhav G, Shah N, Logani A. Revascularization with and without platelet-rich plasma in nonvital, immature, anterior teeth: a pilot clinical study. J Endod. 2012;38:1581–7.PubMedGoogle Scholar
  92. 92.
    Hotwani K, Sharma K. Platelet rich fibrin—a novel acumen into regenerative endodontic therapy. Rest Dent Endod. 2014;39:1–6.Google Scholar
  93. 93.
    Simonpieri A, Del Corso M, Vervelle A, Jimbo R, Inchingolo F, Sammartino G, et al. Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 2: bone graft, implant and reconstructive surgery. Curr Pharm Biotechnol. 2012;13:1231–56.PubMedGoogle Scholar
  94. 94.
    Narang I, Mittal N, Mishra N. A comparative evaluation of the blood clot, platelet-rich plasma, and platelet-rich fibrin in regeneration of necrotic immature permanent teeth: a clinical study. Contemp Clin Dent. 2015;6:63–8.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Zhou R, Wang Y, Chen Y, Chen S, Lyu H, Cai Z, et al. Radiographic, histologic, and biomechanical evaluation of combined application of platelet-rich fibrin with blood clot in regenerative endodontics. J Endod. 2017;43:2034–40.PubMedGoogle Scholar
  96. 96.
    Lolato A, Bucchi C, Taschieri S, Kabbaney AE, Del Fabbro M. Platelet concentrations for revitalization of immature necrotic teeth: a systematic review of the clinical studies. Platelets. (5):383–92.PubMedGoogle Scholar
  97. 97.
    Tziafas D, Alvanou A, Panagiotakopoulos N, Smith AJ, Lesot H, Komnenou A, et al. Induction of odontoblast-like cell differentiation in dog dental pulps after in vivo implantation of dentine matrix components. Arch Oral Biol. 1995;40:883–93.PubMedGoogle Scholar
  98. 98.
    Roberts-Clark DJ, Smith AJ. Angiogenic growth factors in human dentine matrix. Arch Oral Biol. 2000;45:1013–6.PubMedGoogle Scholar
  99. 99.
    Galler KM, D'Souza RN, Federlin M, Cavender AC, Hartgerink JD, Hecker S, et al. Dentin conditioning codetermines cell fate in regenerative endodontics. J Endod. 2011;37:1536–41.PubMedGoogle Scholar
  100. 100.
    Zieris A, Prokoph S, Levental KR, Welzel PB, Grimmer M, Freudenberg U, et al. FGF-2 and VEGF functionalization of starPEG-heparin hydrogels to modulate biomolecular and physical cues of angiogenesis. Biomaterials. 2010;31:7985–94.PubMedGoogle Scholar
  101. 101.
    Galler KM, Hartgerink JD, Cavender AC, Schmalz G, D'Souza RN. A customized self-assembling peptide hydrogel for dental pulp tissue engineering. Tissue Eng Part A. 2012;18:176–84.PubMedGoogle Scholar
  102. 102.
    Silva CR, Babo PS, Gulino M, Costa L, Oliveira JM, Silva-Correia J, et al. Injectable and tunable hyaluronic acid hydrogels releasing chemotactic and angiogenic growth factors for endodontic regeneration. Acta Biomater. 2018. Scholar
  103. 103.
    Nagy MM, Tawfik HE, Hashem AA, Abu-Seida AM. Regenerative potential of immature permanent teeth with necrotic pulps after different regenerative protocols. J Endod. 2014;40:192–8.PubMedGoogle Scholar
  104. 104.
    Takeuchi N, Hayashi Y, Murakami M, Alvarez FJ, Horibe H, Iohara K, et al. Similar in vitro effects and pulp regeneration in ectopic tooth transplantation by basic fibroblast growth factor and granulocyte-colony stimulating factor. Oral Dis. 2015;21:113–22.PubMedGoogle Scholar
  105. 105.
    Iohara K, Imabayashi K, Ishizaka R, Watanabe A, Nabekura J, Ito M, et al. Complete pulp regeneration after pulpectomy by transplantation of CD1051 stem cells with stromal cell-derived factor-1. Tissue Eng Part A. 2011;17:1911–20.PubMedGoogle Scholar
  106. 106.
    Nakashima M, Iohara K, Murakami M, Nakamura H, Sato Y, Ariji Y, et al. Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study. Stem Cell Res Ther. 2017;8:61.PubMedPubMedCentralGoogle Scholar
  107. 107.
    Nakashima M, Iohara K. Recent progress in translation from bench to a pilot clinical study on total pulp regeneration. J Endod. 2017;43:S82–6.PubMedGoogle Scholar
  108. 108.
    Kawamura R, Hayashi Y, Murakami H, Nakashima M. EDTA soluble chemical components and the conditioned medium from mobilized dental pulp stem cells contain an inductive microenvironment, promoting cell proliferation, migration, and odontoblastic differentiation. Stem Cell Res Ther. 2016;7:77.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Henry F. Duncan
    • 1
    Email author
  • Yoshifumi Kobayashi
    • 2
  • Emi Shimizu
    • 2
  1. 1.Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College DublinUniversity of DublinDublinIreland
  2. 2.Oral Biology DepartmentRutgers School of Dental MedicineNewarkUSA

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