Bovine pulp extracellular matrix hydrogel for regenerative endodontic applications: in vitro characterization and in vivo analysis in a necrotic tooth model.
Biomimetic scaffolds
Cell-homing
Dental pulp extracellular matrix hydrogel
Dentin-pulp regeneration
Regenerative endodontics
Journal
Head & face medicine
ISSN: 1746-160X
Titre abrégé: Head Face Med
Pays: England
ID NLM: 101245792
Informations de publication
Date de publication:
22 Oct 2024
22 Oct 2024
Historique:
received:
25
06
2024
accepted:
30
09
2024
medline:
23
10
2024
pubmed:
23
10
2024
entrez:
22
10
2024
Statut:
epublish
Résumé
Regenerative endodontic procedures (REPs) offer the promise of restoring vitality and function to a previously necrotic and infected tooth. However, the nature of regenerated tissues following REPs remains unpredictable and uncontrollable. Decellularized extracellular matrix scaffolds have gained recent attention as scaffolds for regenerative endodontics. Preparation and characterization of a bovine dental pulp-derived extracellular matrix (P-ECM) hydrogel for regenerative endodontic applications. Biocompatibility and regenerative capacity of the prepared scaffold were evaluated in vivo in a canine animal model. Fifteen freshly extracted bovine molar teeth were used to prepare P-ECM hydrogels following approval of the institutional review board of the faculty of dentistry, Alexandria University. Decellularization and lyophilization of the extracted pulp tissues, DNA quantification and histological examination of decellularized P-ECM were done. P-ECM hydrogel was prepared by digestion of decellularized pulps. Prepared scaffolds were evaluated for protein content and release as well as release of VEGF, bFGF, TGF-β1 and BMP2 using ELISA. Rabbit dental pulp stem cells' (rDPSCs) viability in response to P-ECM hydrogels was performed. Finally, proof-of-concept of the regenerative capacity of P-ECM scaffolds was assessed in an infected mature canine tooth model following REPs versus blood clot (BC), injectable platelet-rich fibrin (i-PRF) or hyaluronic acid (HA). Statistical analysis was done using independent t test, the Friedman test and chi-square tests (p value ≤ 0.05). DNA was found to be below the cut-off point (50 ng/mg tissue). Histological evaluation revealed absence of nuclei, retention of glycosaminoglycans (GAGs) and collagen content, respectively. P-ECM hydrogel had a total protein content of (493.12 µg/µl) and protein release was detected up to 14 days. P-ECM hydrogel also retained VEGF, bFGF, TGF-β1 and BMP2. P-ECM hydrogel maintained the viability of rDPSCs as compared to cells cultured under control conditions. P-ECM hydrogel triggered more organized tissues compared to BC, i-PRF and HA when used in REPs for necrotic mature teeth in dogs. Periapical inflammation was significantly less in HA and P-ECM groups compared to blood-derived scaffolds. Bovine dental pulp-derived extracellular matrix (P-ECM) hydrogel scaffold retained its bioactive properties and demonstrated a promising potential in regenerative endodontic procedures compared to conventional blood-derived scaffolds.
Sections du résumé
BACKGROUND
BACKGROUND
Regenerative endodontic procedures (REPs) offer the promise of restoring vitality and function to a previously necrotic and infected tooth. However, the nature of regenerated tissues following REPs remains unpredictable and uncontrollable. Decellularized extracellular matrix scaffolds have gained recent attention as scaffolds for regenerative endodontics.
OBJECTIVES
OBJECTIVE
Preparation and characterization of a bovine dental pulp-derived extracellular matrix (P-ECM) hydrogel for regenerative endodontic applications. Biocompatibility and regenerative capacity of the prepared scaffold were evaluated in vivo in a canine animal model.
METHODS
METHODS
Fifteen freshly extracted bovine molar teeth were used to prepare P-ECM hydrogels following approval of the institutional review board of the faculty of dentistry, Alexandria University. Decellularization and lyophilization of the extracted pulp tissues, DNA quantification and histological examination of decellularized P-ECM were done. P-ECM hydrogel was prepared by digestion of decellularized pulps. Prepared scaffolds were evaluated for protein content and release as well as release of VEGF, bFGF, TGF-β1 and BMP2 using ELISA. Rabbit dental pulp stem cells' (rDPSCs) viability in response to P-ECM hydrogels was performed. Finally, proof-of-concept of the regenerative capacity of P-ECM scaffolds was assessed in an infected mature canine tooth model following REPs versus blood clot (BC), injectable platelet-rich fibrin (i-PRF) or hyaluronic acid (HA). Statistical analysis was done using independent t test, the Friedman test and chi-square tests (p value ≤ 0.05).
RESULTS
RESULTS
DNA was found to be below the cut-off point (50 ng/mg tissue). Histological evaluation revealed absence of nuclei, retention of glycosaminoglycans (GAGs) and collagen content, respectively. P-ECM hydrogel had a total protein content of (493.12 µg/µl) and protein release was detected up to 14 days. P-ECM hydrogel also retained VEGF, bFGF, TGF-β1 and BMP2. P-ECM hydrogel maintained the viability of rDPSCs as compared to cells cultured under control conditions. P-ECM hydrogel triggered more organized tissues compared to BC, i-PRF and HA when used in REPs for necrotic mature teeth in dogs. Periapical inflammation was significantly less in HA and P-ECM groups compared to blood-derived scaffolds.
CONCLUSION
CONCLUSIONS
Bovine dental pulp-derived extracellular matrix (P-ECM) hydrogel scaffold retained its bioactive properties and demonstrated a promising potential in regenerative endodontic procedures compared to conventional blood-derived scaffolds.
Identifiants
pubmed: 39438876
doi: 10.1186/s13005-024-00460-y
pii: 10.1186/s13005-024-00460-y
doi:
Substances chimiques
Hydrogels
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
61Informations de copyright
© 2024. The Author(s).
Références
Wang Y, Zhu X, Zhang C. Pulp revascularization on permanent teeth with open apices in a middle-aged patient. J Endod. 2015;41(9):1571–5.
pubmed: 26071100
doi: 10.1016/j.joen.2015.04.022
Shabbir J, Najmi N, Zehra T, Ali S, Khurshid Z, Zafar MS, et al. Intracanal medicaments. Biomaterials in Endodontics: Elsevier; 2022. pp. 5–81.
Hatipoğlu FP, Hatipoğlu Ö, Taha N, Lehmann AP, Aldhelai TA, Madfa AA, et al. Attitude and practice of regenerative endodontic procedures among endodontists and paediatric dentists: a multinational survey from 13 countries. Int J Pediatr Dent. 2023;33(5):521–34.
doi: 10.1111/ipd.13101
Astudillo-Ortiz E, Babo PS, Sunde PT, Galler KM, Gomez-Florit M, Gomes ME. Endodontic tissue regeneration: a review for tissue engineers and dentists. Tissue Eng Part B: Reviews. 2023;29(5):491–513.
doi: 10.1089/ten.teb.2022.0211
Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: a review of current status and a call for action. J Endod. 2007;33(4):377–90.
pubmed: 17368324
doi: 10.1016/j.joen.2006.09.013
Lin L, Huang GTJ, Sigurdsson A, Kahler B. Clinical cell-based versus cell‐free regenerative endodontics: clarification of concept and term. Int Endod J. 2021;54(6):887–901.
pubmed: 33389773
doi: 10.1111/iej.13471
Zaky SH, Shehabeldin M, Ray H, Sfeir C. The role of inflammation modulation in dental pulp regeneration. Eur Cells Mater. 2021;41:184–93.
doi: 10.22203/eCM.v041a13
Schmalz G, Widbiller M, Galler KM. Clinical perspectives of pulp regeneration. J Endod. 2020;46(9):S161–74.
pubmed: 32950188
doi: 10.1016/j.joen.2020.06.037
Lovelace TW, Henry MA, Hargreaves KM, Diogenes A. Evaluation of the delivery of mesenchymal stem cells into the root canal space of necrotic immature teeth after clinical regenerative endodontic procedure. J Endod. 2011;37(2):133–8.
pubmed: 21238791
doi: 10.1016/j.joen.2010.10.009
Elnawam H, Abdallah A, Nouh S, Khalil NM, Elbackly R. Influence of extracellular matrix scaffolds on histological outcomes of regenerative endodontics in experimental animal models: a systematic review. BMC Oral Health. 2024;24(1):1–26.
doi: 10.1186/s12903-024-04266-x
Alqahtani Q, Zaky SH, Patil A, Beniash E, Ray H, Sfeir C. Decellularized swine dental pulp tissue for regenerative root canal therapy. J Dent Res. 2018;97(13):1460–7.
pubmed: 30067420
doi: 10.1177/0022034518785124
Bakhtiar H, Pezeshki-Modaress M, Kiaipour Z, Shafiee M, Ellini MR, Mazidi A, et al. Pulp ECM-derived macroporous scaffolds for stimulation of dental-pulp regeneration process. Dent Mater. 2020;36(1):76–87.
pubmed: 31735424
doi: 10.1016/j.dental.2019.10.011
Yuan S, Yang X, Wang X, Chen J, Tian W, Yang B. Injectable Xenogeneic Dental Pulp Decellularized Extracellular Matrix Hydrogel promotes functional Dental Pulp Regeneration. Int J Mol Sci. 2023;24(24):17483.
pubmed: 38139310
pmcid: 10743504
doi: 10.3390/ijms242417483
Zheng L, Liu Y, Jiang L, Wang X, Chen Y, Li L, et al. Injectable decellularized dental pulp matrix-functionalized hydrogel microspheres for endodontic regeneration. Acta Biomater. 2023;156:37–48.
pubmed: 36455855
doi: 10.1016/j.actbio.2022.11.047
Johnson TD, DeQuach JA, Gaetani R, Ungerleider J, Elhag D, Nigam V, et al. Human versus porcine tissue sourcing for an injectable myocardial matrix hydrogel. Biomaterials Sci. 2014;2(5):735–44.
doi: 10.1039/C3BM60283D
Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. J Cereb Blood Flow Metabolism. 2020;40(9):1769–77.
doi: 10.1177/0271678X20943823
Bakhtiar H, Rajabi S, Pezeshki-Modaress M, Ellini MR, Panahinia M, Alijani S, et al. Optimizing methods for bovine dental pulp decellularization. J Endod. 2021;47(1):62–8.
pubmed: 33049226
doi: 10.1016/j.joen.2020.08.027
Galante R, Pinto TJ, Colaco R, Serro AP. Sterilization of hydrogels for biomedical applications: a review. J Biomedical Mater Res Part B: Appl Biomaterials. 2018;106(6):2472–92.
doi: 10.1002/jbm.b.34048
Galante R, Rediguieri CF, Kikuchi IS, Vasquez PA, Colaço R, Serro AP, et al. About the sterilization of chitosan hydrogel nanoparticles. PLoS ONE. 2016;11(12):e0168862.
pubmed: 28002493
pmcid: 5176313
doi: 10.1371/journal.pone.0168862
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–5.
pubmed: 22930834
pmcid: 5554542
doi: 10.1038/nmeth.2089
El-Backly RM, Massoud AG, El‐Badry AM, Sherif RA, Marei MK. Regeneration of dentine/pulp‐like tissue using a dental pulp stem cell/poly (lactic‐co‐glycolic) acid scaffold construct in New Zealand white rabbits. Australian Endodontic J. 2008;34(2):52–67.
doi: 10.1111/j.1747-4477.2008.00139.x
Kim SG, Solomon CS. Regenerative endodontic therapy in mature teeth using human-derived composite amnion-chorion membrane as a bioactive scaffold: a pilot animal investigation. J Endod. 2021;47(7):1101–9.
pubmed: 33887306
doi: 10.1016/j.joen.2021.04.010
Miron RJ, Fujioka-Kobayashi M, Hernandez M, Kandalam U, Zhang Y, Ghanaati S, et al. Injectable platelet rich fibrin (i-PRF): opportunities in regenerative dentistry? Clin Oral Invest. 2017;21:2619–27.
doi: 10.1007/s00784-017-2063-9
Endodontists AAo. AAE Clinical Considerations for a Regenerative Procedure 2021 [ https://www.aae.org/specialty/wp-content/uploads/sites/2/2021/08/ClinicalConsiderationsApprovedByREC062921.pdf
Huang Y, Tang X, Cehreli ZC, Dai X, Xu J, Zhu H. Autologous transplantation of deciduous tooth pulp into necrotic young permanent teeth for pulp regeneration in a dog model. J Int Med Res. 2019;47(10):5094–105.
pubmed: 31364449
pmcid: 6833418
doi: 10.1177/0300060519862094
Yoo Y-J, Perinpanayagam H, Choi Y, Gu Y, Chang S-W, Baek S-H, et al. Characterization of histopathology and microbiota in contemporary regenerative endodontic procedures: still coming up short. J Endod. 2021;47(8):1285–93. e1.
pubmed: 34044040
doi: 10.1016/j.joen.2021.05.006
Chinen K, Tokuda Y, Aoki M. Clinical problem solving: diagnostic power of gram stain examination. Gen Med. 2009;10(1):3–6.
doi: 10.14442/general.10.3
Avinash T, Sandhya T, Bhalerao S, Uma M, Salunkhe G, Sonali R. Study of Microflora in Pulp tissue of Carious Teeth using Gram Stain. Int J Curr Microbiol App Sci. 2014;3(9):539–51.
Gathani KM, Raghavendra SS. Scaffolds in regenerative endodontics: a review. Dent Res J. 2016;13(5):379.
doi: 10.4103/1735-3327.192266
Alqahtani Q, Zaky S, Patil A, Beniash E, Ray H, Sfeir C. Decellularized swine dental pulp tissue for regenerative root canal therapy. J Dent Res. 2018;97(13):1460–7.
pubmed: 30067420
doi: 10.1177/0022034518785124
Badylak SF, Freytes DO, Gilbert TW. Extracellular matrix as a biological scaffold material: structure and function. Acta Biomater. 2009;5(1):1–13.
pubmed: 18938117
doi: 10.1016/j.actbio.2008.09.013
Singh H, Rathee K, Kaur A, Miglani N. Pulp regeneration in an immature maxillary central incisor using hyaluronic acid hydrogel. Contemp Clin Dent. 2021;12(1):94.
pubmed: 33967547
pmcid: 8092086
doi: 10.4103/ccd.ccd_149_20
Jiang X, Liu H, Peng C. Clinical and radiographic assessment of the efficacy of a collagen membrane in regenerative endodontics: a randomized, controlled clinical trial. J Endod. 2017;43(9):1465–71.
pubmed: 28716215
doi: 10.1016/j.joen.2017.04.011
AlHowaish NA, AlSudani DI, Khounganian R, AlMuraikhi N. Histological evaluation of restylane lyft used as a scaffold for dental pulp regeneration in non-infected immature teeth in dogs. Materials. 2022;15(12):4095.
pubmed: 35744154
pmcid: 9228365
doi: 10.3390/ma15124095
Marler JJ, Guha A, Rowley J, Koka R, Mooney D, Upton J, et al. Soft-tissue augmentation with injectable alginate and syngeneic fibroblasts. Plast Reconstr Surg. 2000;105(6):2049–58.
pubmed: 10839402
doi: 10.1097/00006534-200005000-00020
Guo X, Li J, Wu Y, Xu L. Recent advancements in hydrogels as novel tissue engineering scaffolds for dental pulp regeneration. Int J Biol Macromol. 2024;264:130708.
Matoug-Elwerfelli M, Duggal M, Nazzal H, Esteves F, Raïf E. A biocompatible decellularized pulp scaffold for regenerative endodontics. Int Endod J. 2018;51(6):663–73.
pubmed: 29197101
doi: 10.1111/iej.12882
Matoug-Elwerfelli M, Nazzal H, Raif EM, Wilshaw S-P, Esteves F, Duggal M. Ex-vivo recellularisation and stem cell differentiation of a decellularised rat dental pulp matrix. Sci Rep. 2020;10(1):21553.
pubmed: 33299073
pmcid: 7725831
doi: 10.1038/s41598-020-78477-x
Simon S, Smith AJ, Lumley PJ, Cooper PR, Berdal A. The pulp healing process: from generation to regeneration. Endodontic Top. 2012;26(1):41–56.
doi: 10.1111/etp.12019
Six N, Decup F, Lasfargues J-J, Salih E, Goldberg M. Osteogenic proteins (bone sialoprotein and bone morphogenetic protein-7) and dental pulp mineralization. J Mater Science: Mater Med. 2002;13(2):225–32.
Goldberg M, Njeh A, Uzunoglu E. Is pulp inflammation a prerequisite for pulp healing and regeneration? Mediators of inflammation. 2015;2015.
Virtej A, Løes S, Iden O, Bletsa A, Berggreen E. Vascular endothelial growth factors signalling in normal human dental pulp: a study of gene and protein expression. Eur J Oral Sci. 2013;121(2):92–100.
pubmed: 23489898
doi: 10.1111/eos.12019
Vaseenon S, Chattipakorn N, Chattipakorn SC. The possible role of basic fibroblast growth factor in dental pulp. Arch Oral Biol. 2020;109:104574.
pubmed: 31585238
doi: 10.1016/j.archoralbio.2019.104574
Piattelli A, Rubini C, Fioroni M, Tripodi D, Strocchi R. Transforming growth factor-beta 1 (TGF‐beta 1) expression in normal healthy pulps and in those with irreversible pulpitis. Int Endod J. 2004;37(2):114–9.
pubmed: 14871177
doi: 10.1111/j.0143-2885.2004.00758.x
Ilić J, Radović K, Roganović J, Brković B, Stojić D. The levels of vascular endothelial growth factor and bone morphogenetic protein 2 in dental pulp tissue of healthy and diabetic patients. J Endod. 2012;38(6):764–8.
pubmed: 22595109
doi: 10.1016/j.joen.2012.03.016
Aksel H, Öztürk Ş, Serper A, Ulubayram K. VEGF/BMP-2 loaded three‐dimensional model for enhanced angiogenic and odontogenic potential of dental pulp stem cells. Int Endod J. 2018;51(4):420–30.
pubmed: 29080346
doi: 10.1111/iej.12869
Kang W, Liang Q, Du L, Shang L, Wang T, Ge S. Sequential application of bFGF and BMP-2 facilitates osteogenic differentiation of human periodontal ligament stem cells. J Periodontal Res. 2019;54(4):424–34.
pubmed: 30851068
doi: 10.1111/jre.12644
Zhang R, Xie L, Wu H, Yang T, Zhang Q, Tian Y, et al. Alginate/laponite hydrogel microspheres co-encapsulating dental pulp stem cells and VEGF for endodontic regeneration. Acta Biomater. 2020;113:305–16.
pubmed: 32663663
doi: 10.1016/j.actbio.2020.07.012
Yadlapati M, Biguetti C, Cavalla F, Nieves F, Bessey C, Bohluli P, et al. Characterization of a vascular endothelial growth factor–loaded bioresorbable delivery system for pulp regeneration. J Endod. 2017;43(1):77–83.
pubmed: 27939739
doi: 10.1016/j.joen.2016.09.022
Li C-Y, Prochazka J, Goodwin AF, Klein OD. Fibroblast growth factor signaling in mammalian tooth development. Odontology. 2014;102:1–13.
pubmed: 24343791
doi: 10.1007/s10266-013-0142-1
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(1–2):176–84.
pubmed: 21827280
doi: 10.1089/ten.tea.2011.0222
Chang Y-C, Chang M-C, Chen Y-J, Liou J-U, Chang H-H, Huang W-L, et al. Basic fibroblast growth factor regulates gene and protein expression related to proliferation, differentiation, and matrix production of human dental pulp cells. J Endod. 2017;43(6):936–42.
pubmed: 28416318
doi: 10.1016/j.joen.2017.01.024
Mathieu S, Jeanneau C, Sheibat-Othman N, Kalaji N, Fessi H, About I. Usefulness of controlled release of growth factors in investigating the early events of dentin-pulp regeneration. J Endod. 2013;39(2):228–35.
pubmed: 23321236
doi: 10.1016/j.joen.2012.11.007
Iohara K, Nakashima M, Ito M, Ishikawa M, Nakasima A, Akamine A. Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2. J Dent Res. 2004;83(8):590–5.
pubmed: 15271965
doi: 10.1177/154405910408300802
Yang W, Harris M, Cui Y, Mishina Y, Harris S, Gluhak-Heinrich J. Bmp2 is required for odontoblast differentiation and pulp vasculogenesis. J Dent Res. 2012;91(1):58–64.
pubmed: 21984706
pmcid: 3232115
doi: 10.1177/0022034511424409
Gonçalves LF, Fernandes AP, Cosme-Silva L, Colombo FA, Martins NS, Oliveira TM, et al. Effect of EDTA on TGF-β1 released from the dentin matrix and its influence on dental pulp stem cell migration. Brazilian oral Res. 2016;30:e131.
doi: 10.1590/1807-3107bor-2016.vol30.0131
Galler K, Widbiller M, Buchalla W, Eidt A, Hiller KA, Hoffer P, et al. EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells. Int Endod J. 2016;49(6):581–90.
pubmed: 26114662
doi: 10.1111/iej.12492
Suchánek J, Soukup T, Ivancakova R, Karbanová J, Hubková V, Pytlík R, et al. Human dental pulp stem cells-isolation and long term cultivation. ACTA MEDICA-HRADEC KRALOVE-. 2007;50(3):195.
pubmed: 18254273
Johnson KE, Wilgus TA. Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Adv Wound care. 2014;3(10):647–61.
doi: 10.1089/wound.2013.0517
Nagaraja S, Mathew S, Abraham A, Ramesh P, Chandanala S. Evaluation of vascular endothelial growth factor–A release from platelet-rich fibrin, platelet-rich fibrin matrix, and dental pulp at different time intervals. J Conservative Dentistry Endodontics. 2020;23(4):359–63.
doi: 10.4103/JCD.JCD_465_19
Tran-Hung L, Laurent P, Camps J, About I. Quantification of angiogenic growth factors released by human dental cells after injury. Arch Oral Biol. 2008;53(1):9–13.
pubmed: 17764655
doi: 10.1016/j.archoralbio.2007.07.001
Kim Y-S, Min K-S, Jeong D-H, Jang J-H, Kim H-W, Kim E-C. Effects of fibroblast growth factor-2 on the expression and regulation of chemokines in human dental pulp cells. J Endod. 2010;36(11):1824–30.
pubmed: 20951295
doi: 10.1016/j.joen.2010.08.020
Laurent P, Camps J, About I. BiodentineTM induces TGF-β1 release from human pulp cells and early dental pulp mineralization. Int Endod J. 2012;45(5):439–48.
pubmed: 22188368
doi: 10.1111/j.1365-2591.2011.01995.x
Begue-Kirn C, Smith AJ, Loriot M, Kupferle C, Ruch J, Lesot H. Comparative analysis of TGFsss, BMPs, IGF1, msxs, fibronectin, osteonectin and bone sialoprotein gene expression during normal and in vitro-induced odontoblast differentiation. Int J Dev Biol. 1994;38:405.
pubmed: 7848824
Abdul Khodir WKW, Abdul Razak AH, Ng MH, Guarino V, Susanti D. Encapsulation and characterization of gentamicin sulfate in the collagen added electrospun nanofibers for skin regeneration. J Funct Biomaterials. 2018;9(2):36.
doi: 10.3390/jfb9020036
Alenazy MS, Al-Nazhan S, Mosadomi HA. Histologic, radiographic, and micro-computed tomography evaluation of experimentally enlarged root apices in dog teeth with apical periodontitis after regenerative treatment. Curr Therapeutic Res. 2021;94:100620.
doi: 10.1016/j.curtheres.2020.100620
Nakashima M, Iohara K, Bottino MC, Fouad AF, Nör JE, Huang GT-J. Animal models for stem cell-based pulp regeneration: foundation for human clinical applications. Tissue Eng Part B: Reviews. 2019;25(2):100–13.
doi: 10.1089/ten.teb.2018.0194
Holland R, Otoboni Filho JA, de Souza V, Nery MJ, Bernabé PFE, Dezan E Jr. A comparison of one versus two appointment endodontic therapy in dogs’ teeth with apical periodontitis. J Endod. 2003;29(2):121–4.
pubmed: 12597712
doi: 10.1097/00004770-200302000-00009
Laureys WG, Cuvelier CA, Dermaut LR, De Pauw GA. The critical apical diameter to obtain regeneration of the pulp tissue after tooth transplantation, replantation, or regenerative endodontic treatment. J Endod. 2013;39(6):759–63.
pubmed: 23683275
doi: 10.1016/j.joen.2013.02.004
Saoud TM, Martin G, Chen Y-HM, Chen K-L, Chen C-A, Songtrakul K, et al. Treatment of mature permanent teeth with necrotic pulps and apical periodontitis using regenerative endodontic procedures: a case series. J Endod. 2016;42(1):57–65.
pubmed: 26525552
doi: 10.1016/j.joen.2015.09.015
El-Kateb NM, El-Backly RN, Amin WM, Abdalla AM. Quantitative assessment of intracanal regenerated tissues after regenerative endodontic procedures in mature teeth using magnetic resonance imaging: a randomized controlled clinical trial. J Endod. 2020;46(5):563–74.
pubmed: 32173020
doi: 10.1016/j.joen.2020.01.026
Estefan BS, El Batouty KM, Nagy MM, Diogenes A. Influence of age and apical diameter on the success of endodontic regeneration procedures. J Endod. 2016;42(11):1620–5.
pubmed: 27623497
doi: 10.1016/j.joen.2016.06.020
Sakamoto M, Siqueira J Jr, Rôças I, Benno Y. Bacterial reduction and persistence after endodontic treatment procedures. Oral Microbiol Immunol. 2007;22(1):19–23.
pubmed: 17241166
doi: 10.1111/j.1399-302X.2007.00315.x
Menzies RA, Reiter AM, Lewis JR. Assessment of apical periodontitis in dogs and humans: a review. J Vet Dent. 2014;31(1):8–21.
pubmed: 24902408
doi: 10.1177/089875641403100101
Smith J, Smith A, Shelton R, Cooper P. Antibacterial activity of dentine and pulp extracellular matrix extracts. Int Endod J. 2012;45(8):749–55.
pubmed: 22416895
doi: 10.1111/j.1365-2591.2012.02031.x
Eldessoky AE, Khalefa MM, Abu-Seida AM. Regenerative endodontic therapy in mature teeth with necrotic pulp and apical periodontitis using two disinfection protocols. BMC Oral Health. 2023;23(1):163.
pubmed: 36949460
pmcid: 10031861
doi: 10.1186/s12903-023-02863-w
Cooper PR, Holder MJ, Smith AJ. Inflammation and regeneration in the dentin-pulp complex: a double-edged sword. J Endod. 2014;40(4):S46–51.
pubmed: 24698693
doi: 10.1016/j.joen.2014.01.021
Lin L, Rosenberg P. Repair and regeneration in endodontics. Int Endod J. 2011;44(10):889–906.
pubmed: 21718337
doi: 10.1111/j.1365-2591.2011.01915.x
Litwiniuk M, Krejner A, Speyrer MS, Gauto AR, Grzela T. Hyaluronic acid in inflammation and tissue regeneration. Wounds. 2016;28(3):78–88.
pubmed: 26978861
Vasvani S, Kulkarni P, Rawtani D. Hyaluronic acid: a review on its biology, aspects of drug delivery, route of administrations and a special emphasis on its approved marketed products and recent clinical studies. Int J Biol Macromol. 2020;151:1012–29.
pubmed: 31715233
doi: 10.1016/j.ijbiomac.2019.11.066
Schmidt J, Pilbauerova N, Soukup T, Suchankova-Kleplova T, Suchanek J. Low molecular weight hyaluronic acid effect on dental pulp stem cells in vitro. Biomolecules. 2020;11(1):22.
pubmed: 33379324
pmcid: 7823925
doi: 10.3390/biom11010022
Chrepa V, Austah O, Diogenes A. Evaluation of a commercially available hyaluronic acid hydrogel (restylane) as injectable scaffold for dental pulp regeneration: an in vitro evaluation. J Endod. 2017;43(2):257–62.
pubmed: 28041686
doi: 10.1016/j.joen.2016.10.026
Shumate GT, Chopra R, Jones D, Messina DJ, Hee CK. In vivo degradation of crosslinked hyaluronic acid fillers by exogenous hyaluronidases. Dermatol Surg. 2018;44(8):1075–83.
pubmed: 29659410
doi: 10.1097/DSS.0000000000001525
Sundaram H, Voigts B, Beer K, Meland M. Comparison of the rheological properties of viscosity and elasticity in two categories of soft tissue fillers: calcium hydroxylapatite and hyaluronic acid. Dermatol Surg. 2010;36:1859–65.
pubmed: 20969663
doi: 10.1111/j.1524-4725.2010.01743.x
AlHowaish NA, AlSudani DI, AlMuraikhi NA. Evaluation of a hyaluronic acid hydrogel (Restylane Lyft) as a scaffold for dental pulp regeneration in a regenerative endodontic organotype model. Odontology. 2022;110(4):726–34.
pubmed: 35471745
doi: 10.1007/s10266-022-00710-y
Palma PJ, Ramos JC, Martins JB, Diogenes A, Figueiredo MH, Ferreira P, et al. Histologic evaluation of regenerative endodontic procedures with the use of chitosan scaffolds in immature dog teeth with apical periodontitis. J Endod. 2017;43(8):1279–87.
pubmed: 28577961
doi: 10.1016/j.joen.2017.03.005
Schmidt J, Pavlík V, Suchánek J, Nešporová K, Soukup T, Kapitán M, et al. Low, medium, and high molecular weight hyaluronic acid effects on human dental pulp stem cells in vitro. Int J Biol Macromol. 2023;253:127220.
pubmed: 37827401
doi: 10.1016/j.ijbiomac.2023.127220
Schlie-Wolter S, Ngezahayo A, Chichkov BN. The selective role of ECM components on cell adhesion, morphology, proliferation and communication in vitro. Exp Cell Res. 2013;319(10):1553–61.
pubmed: 23588204
doi: 10.1016/j.yexcr.2013.03.016
Gomes-Filho JE, Duarte PCT, Ervolino E, Bomfim SRM, Abimussi CJX, da Silva Santos LM, et al. Histologic characterization of engineered tissues in the canal space of closed-apex teeth with apical periodontitis. J Endod. 2013;39(12):1549–56.
pubmed: 24238445
doi: 10.1016/j.joen.2013.08.023
Fouad AF. Contemporary microbial and antimicrobial considerations in regenerative endodontic therapy. J Endod. 2020;46(9):S105–14.
pubmed: 32950182
doi: 10.1016/j.joen.2020.06.030
Vishwanat L, Duong R, Takimoto K, Phillips L, Espitia CO, Diogenes A, et al. Effect of bacterial biofilm on the osteogenic differentiation of stem cells of apical papilla. J Endod. 2017;43(6):916–22.
pubmed: 28416302
doi: 10.1016/j.joen.2017.01.023
Almutairi W, Yassen GH, Aminoshariae A, Williams KA, Mickel A. Regenerative endodontics: a systematic analysis of the failed cases. J Endod. 2019;45(5):567–77.
pubmed: 30905573
doi: 10.1016/j.joen.2019.02.004
Ballal NV, Narkedamalli R, Ruparel NB, Shenoy PA, Bhat VR, Belle VS. Effect of Maleic Acid Root conditioning on release of transforming growth factor Beta 1 from infected Root Canal dentin. J Endod. 2022;48(5):620–4.
pubmed: 35217129
doi: 10.1016/j.joen.2022.02.007
Kim SG. Infection and pulp regeneration. Dentistry J. 2016;4(1):4.
doi: 10.3390/dj4010004
Iranmanesh P, Torabinejad M, Saatchi M, Toghraie D, Razavi SM, Khademi A. Effect of duration of root canal infection on the ability of dentin-pulp complex regeneration of immature permanent teeth: an animal study. J Endod. 2022;48(10):1301–7. e2.
pubmed: 35933045
doi: 10.1016/j.joen.2022.07.007
Meschi N, Palma PJ, Cabanillas-Balsera D. Effectiveness of revitalization in treating apical periodontitis: a systematic review and meta‐analysis. Int Endod J. 2023;56:510–32.
pubmed: 35579093
doi: 10.1111/iej.13778
Ahmed HMA, El-Karim I, Duncan HF, Krastl G, Galler K. Implications of root, pulp chamber, and canal anatomy on pulpotomy and revitalization procedures. Clin Oral Invest. 2023;27(11):6357–69.
doi: 10.1007/s00784-023-05284-9
Agrawal V, Johnson SA, Reing J, Zhang L, Tottey S, Wang G et al. Epimorphic regeneration approach to tissue replacement in adult mammals. Proceedings of the National Academy of Sciences. 2010;107(8):3351-5.
Badylak SF, Taylor D, Uygun K. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng. 2011;13:27–53.
pubmed: 21417722
pmcid: 10887492
doi: 10.1146/annurev-bioeng-071910-124743
Palma PJ, Martins J, Diogo P, Sequeira D, Ramos JC, Diogenes A, et al. Does apical papilla survive and develop in apical periodontitis presence after regenerative endodontic procedures? Appl Sci. 2019;9(19):3942.
doi: 10.3390/app9193942
Scelza P, Gonçalves F, Caldas I, Nunes F, Lourenço ES, Tavares S, et al. Prognosis of regenerative endodontic procedures in mature teeth: a systematic review and meta-analysis of clinical and radiographic parameters. Materials. 2021;14(16):4418.
pubmed: 34442940
pmcid: 8398537
doi: 10.3390/ma14164418
Lu J, Liu H, Lu Z, Kahler B, Lin LM. Regenerative endodontic procedures for traumatized immature permanent teeth with severe external root resorption and root perforation. J Endod. 2020;46(11):1610–5.
pubmed: 32730858
doi: 10.1016/j.joen.2020.07.022