Clinical and radiographic evaluation of regenerative endodontic procedures (REPs) with or without concentrated growth factor (CGF) as scaffolds for non-vital immature mandibular premolars

This study aimed to perform clinical and radiographic investigations of the effect of regenerative endodontic procedures (REPs) with and without concentrated growth factor (CGF). Fifty-six non-vital and immature teeth from 56 patients were randomly categorized into two groups. Following chemical and mechanical preparation, REPs with and without CGF as a scaffold was induced in the blood clot (BLC) group and the CGF group. All patients were clinically and radiographically evaluated at 6-month and 12-month intervals to monitor their progress and treatment outcomes. When considering the total number of patients, the follow-up rate was 96.4% (54 out of 56 patients) over a 12-month period. Favorable clinical and radiographic outcomes were observed in 92.6% of patients (25 out of 27) in both the CGF and BLC groups; there were no significant differences between the two groups in these respects (p > 0.05). Notable differences were, however, observed in radiographic measurements relating to the development of root length and radiographic root area when compared between the CGF and BLC groups at both the 6-month and 12-month follow-up intervals (p < 0.05). REPs have been proven to represent a conservative and effective approach for promoting maturogenesis in non-vital and immature teeth. Furthermore, the incorporation of CGF as scaffolds holds promising potential for enhancing the desired biological outcomes of this regenerative technique. These findings highlight the clinical significance and potential benefits of CGF supplementation in REPs, further supporting its application in the field of endodontics.

Maturogenesis; Concentrated growth factor; Immature teeth; Revascularization

[1] Meschi N, EzEldeen M, Garcia AET, Lahoud P, Van Gorp G, Coucke W, et al. Regenerative endodontic procedure of immature permanent teeth with leukocyte and platelet-rich fibrin: a multicenter controlled clinical trial. Journal of Endodontics. 2021; 47: 1729–1750.

[2] Lee C, Song M. Failure of regenerative endodontic procedures: case analysis and subsequent treatment options. Journal of Endodontics. 2022; 48: 1137–1145.

[3] Östby BN. The role of the blood clot in endodontic therapy an experimental histologic study. Acta Odontologica Scandinavica. 1961; 19: 323–353.

[4] Nygaard-Östby B, Hjortdal O. Tissue formation in the root canal following pulp removal. European Journal of Oral Sciences. 1971; 79: 333–349.

[5] Cymerman JJ, Nosrat A. Regenerative endodontic treatment as a biologically based approach for non-surgical retreatment of immature teeth. Journal of Endodontics. 2020; 46: 44–50.

[6] Murray PE. Review of guidance for the selection of regenerative endodontics, apexogenesis, apexification, pulpotomy, and other endodontic treatments for immature permanent teeth. International Endodontic Journal. 2023; 56: 188–199.

[7] Li L, Pan Y, Mei L, Li J. Clinical and radiographic outcomes in immature permanent necrotic evaginated teeth treated with regenerative endodontic procedures. Journal of Endodontics. 2017; 43: 246–251.

[8] Arslan H, Ahmed HMA, Şahin Y, Doğanay Yıldız E, Gündoğdu EC, Güven Y, et al. Regenerative endodontic procedures in necrotic mature teeth with periapical radiolucencies: a preliminary randomized clinical study. Journal of Endodontics. 2019; 45: 863–872.

[9] Ahmed YE, Ahmed GM, Ghoneim AG. Evaluation of postoperative pain and healing following regenerative endodontics using platelet‐rich plasma versus conventional endodontic treatment in necrotic mature mandibular molars with chronic periapical periodontitis. a randomized clinical trial. International Endodontic Journal. 2023; 56: 404–418.

[10] Xie Z, Shen Z, Zhan P, Yang J, Huang Q, Huang S, et al. Functional dental pulp regeneration: basic research and clinical translation. International Journal of Molecular Sciences. 2021; 22: 8991.

[11] Liang C, Liao L, Tian W. Stem cell-based dental pulp regeneration: insights from signaling pathways. Stem Cell Reviews and Reports. 2021; 17: 1251–1263.

[12] Kim SG. A cell-based approach to dental pulp regeneration using mesenchymal stem cells: a scoping review. International Journal of Molecular Sciences. 2021; 22: 4357.

[13] Eramo S, Natali A, Pinna R, Milia E. Dental pulp regeneration via cell homing. International Endodontic Journal. 2018; 51: 405–419.

[14] Ahmed GM, Abouauf EA, AbuBakr N, Fouad AM, Dörfer CE, Fawzy El-Sayed KM. Cell-based transplantation versus cell homing approaches for pulp-dentin complex regeneration. Stem Cells International. 2021; 2021: 1–23.

[15] Ziauddin SM, Nakashima M, Watanabe H, Tominaga M, Iohara K. Biological characteristics and pulp regeneration potential of stem cells from canine deciduous teeth compared with those of permanent teeth. Stem Cell Research & Therapy. 2022; 13: 439.

[16] Tabatabaei F, Aghamohammadi Z, Tayebi L. In vitro and in vivo effects of concentrated growth factor on cells and tissues. Journal of Biomedical Materials Research Part A. 2020; 108: 1338–1350.

[17] Li Z, Liu L, Wang L, Song D. The effects and potential applications of concentrated growth factor in dentin-pulp complex regeneration. Stem Cell Research & Therapy. 2021; 12: 357.

[18] Rodella LF, Favero G, Boninsegna R, Buffoli B, Labanca M, Scarì G, et al. Growth factors, CD34 positive cells, and fibrin network analysis in concentrated growth factors fraction. Microscopy Research and Technique. 2011; 74: 772–777.

[19] Jin R, Song G, Chai J, Gou X, Yuan G, Chen Z. Effects of concentrated growth factor on proliferation, migration, and differentiation of human dental pulp stem cells in vitro. Journal of Tissue Engineering. 2018; 9: 2041731418817505.

[20] Kavitha M, Sivaprakasam SP, Arunaraj D, Hemamalini R, Velayudham S, Bakthavatchalam B. Comparative evaluation of platelet-rich fibrin and concentrated growth factor as scaffolds in regenerative endodontic procedure: a randomized controlled clinical trial. The Journal of Contemporary Dental Practice. 2023; 23: 1211–1217.

[21] Murray PE. Platelet-rich plasma and platelet-rich fibrin can induce apical closure more frequently than blood-clot revascularization for the regeneration of immature permanent teeth: a meta-analysis of clinical efficacy. Frontiers in Bioengineering and Biotechnology. 2018; 6: 139.

[22] Bose R, Nummikoski P, Hargreaves K. A retrospective evaluation of radiographic outcomes in immature teeth with necrotic root canal systems treated with regenerative endodontic procedures. Journal of Endodontics. 2009; 35: 1343–1349.

[23] ElSheshtawy AS, Nazzal H, El Shahawy OI, El Baz AA, Ismail SM, Kang J, et al. The effect of platelet-rich plasma as a scaffold in regeneration/revitalization endodontics of immature permanent teeth assessed using 2-dimensional radiographs and cone beam computed tomography: a randomized controlled trial. International Endodontic Journal. 2020; 53: 905–921.

[24] Jun J, Chun K, Kum K, Lee W, Shon W, Yoo Y, et al. Effect of mineral trioxide aggregate plug location on root development in regenerative endodontic procedure. Odontology. 2021; 109: 411–421.

[25] Youssef A, Ali M, ElBolok A, Hassan R. Regenerative endodontic procedures for the treatment of necrotic mature teeth: a preliminary randomized clinical trial. International Endodontic Journal. 2022; 55: 334–346.

[26] Duncan HF. Present status and future directions—vital pulp treatment and pulp preservation strategies. International Endodontic Journal. 2022; 55: 497–511.

[27] Kim SG, Malek M, Sigurdsson A, Lin LM, Kahler B. Regenerative endodontics: a comprehensive review. International Endodontic Journal. 2018; 51: 1367–1388.

[28] Wu DT, Munguia-Lopez JG, Cho YW, Ma X, Song V, Zhu Z, et al. Polymeric scaffolds for dental, oral, and craniofacial regenerative medicine. Molecules. 2021; 26: 7043.

[29] Liu Y, Liu Y, Zeng C, Li W, Ke C, Xu S. Concentrated growth factor promotes wound healing potential of HaCaT cells by activating the RAS signaling pathway. Frontiers in Bioscience. 2022; 27: 319.

[30] Shetty H, Shetty S, Kakade A, Mali S, Shetty A, Neelakantan P. Three-dimensional qualitative and quantitative analyses of the effect of periradicular lesions on the outcome of regenerative endodontic procedures: a prospective clinical study. Clinical Oral Investigations. 2021; 25: 691–700.

[31] Rodella LF, Favero G, Boninsegna R, Borgonovo A, Rezzani R, Santoro F. TGF-beta1 and VEGF after fresh frozen bone allograft insertion in oral-maxillo-facial surgery. Histology and Histopathology. 2010; 25: 463–471.

[32] Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Pietrzkowski Z, Kowalska MA, et al. Numerous growth factors, cytokines, and chemokines are secreted by human CD34+ cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood. 2001; 97: 3075–3085.

[33] Masuki H, Okudera T, Watanebe T, Suzuki M, Nishiyama K, Okudera H, et al. Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (a-PRF), and concentrated growth factors (CGF). International Journal of Implant Dentistry. 2016; 2: 19.

[34] Bosshardt DD, Stadlinger B, Terheyden H. Cell-to-cell communication-periodontal regeneration. Clinical Oral Implants Research. 2015; 26: 229–239.