Int J Stomatol ›› 2021, Vol. 48 ›› Issue (2): 192-197.doi: 10.7518/gjkq.2021029

• Reviews • Previous Articles     Next Articles

Research progress on hydrogels for pulp regeneration

Cao Chunling(),Han Bing,Wang Xiaoyan()   

  1. Dept. of Cariology and Endodontics, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
  • Received:2020-07-02 Revised:2020-11-16 Online:2021-03-01 Published:2021-03-17
  • Contact: Xiaoyan Wang;
  • Supported by:
    National Natural Science Foundation of China(81771061);National Natural Science Foundation of China(81400562)


Hydrogel is a soft, biocompatible polymer network system that can be used as a scaffold in tissue engineering. Using the principles of tissue engineering, dental pulp stem cells cultured in vitro can be implanted into biocompatible, degradable scaffolds, and induced to form pulp-dentin complex and dental pulp-like tissue. Hydrogel scaffolds simulate the extracellular microenvironment and transmit signal molecules, representing a promising material for pulp regeneration. This study reviews the applications of hydrogels with different compositions and properties for pulp regeneration.

Key words: hydrogel, scaffold, pulp regeneration, tissue engineering

CLC Number: 

  • R782.2

[1] Moshaverinia A, Chen C, Akiyama K, et al. Alginate hydrogel as a promising scaffold for dental-derived stem cells: an in vitro study[J]. J Mater Sci Mater Med, 2012,23(12):3041-3051.
doi: 10.1007/s10856-012-4759-3 pmid: 22945383
[2] Lee KY, Mooney DJ. Alginate: properties and biomedical applications[J]. Prog Polym Sci, 2012,37(1):106-126.
[3] Dobie K, Smith G, Sloan AJ, et al. Effects of alginate hydrogels and TGF-beta 1 on human dental pulp repair in vitro[J]. Connect Tissue Res, 2002,43(2/3):387-390.
[4] Erisken C, Kalyon DM, Zhou J, et al. Viscoelastic properties of dental pulp tissue and ramifications on biomaterial development for pulp regeneration[J]. J Endod, 2015,41(10):1711-1717.
[5] Piva E, Silva AF, Nör JE. Functionalized scaffolds to control dental pulp stem cell fate[J]. J Endod, 2014,40(4 Suppl):S33-S40.
doi: 10.1016/j.joen.2014.01.013 pmid: 24698691
[6] 胡杨, 余小月, 但卫华, 等. 胶原基水凝胶的制备、结构性能表征及其在生物医学中的应用[J]. 功能材料, 2017,48(1):1038-1046.
Hu Y, Yu XY, Dan WH, et al. Preparation, characte-rization and biomedical applications of collagen ba-sed hydrogels[J]. J Funct Mater, 2017,48(1):1038-1046.
[7] Yang CL, Hillas PJ, Báez JA, et al. The application of recombinant human collagen in tissue engineering[J]. BioDrugs, 2004,18(2):103-119.
[8] Rosa V, Zhang Z, Grande RH, et al. Dental pulp tissue engineering in full-length human root canals[J]. J Dent Res, 2013,92(11):970-975.
pmid: 24056227
[9] Yuan L, Li B, Yang JR, et al. Effects of composition and mechanical property of injectable collagen Ⅰ/Ⅱ composite hydrogels on chondrocyte behaviors[J]. Tissue Eng Part A, 2016,22(11/12):899-906.
[10] Suzuki T, Lee CH, Chen M, et al. Induced migration of dental pulp stem cells for in vivo pulp regeneration[J]. J Dent Res, 2011,90(8):1013-1018.
doi: 10.1177/0022034511408426
[11] Khetan S, Guvendiren M, Legant WR, et al. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels[J]. Nat Mater, 2013,12(5):458-465.
doi: 10.1038/nmat3586 pmid: 23524375
[12] Darr A, Calabro A. Synjournal and characterization of tyramine-based hyaluronan hydrogels[J]. J Mater Sci Mater Med, 2009,20(1):33-44.
doi: 10.1007/s10856-008-3540-0 pmid: 18668211
[13] Lambricht L, De Berdt P, Vanacker J, et al. The type and composition of alginate and hyaluronic-based hydrogels influence the viability of stem cells of the apical papilla[J]. Dent Mater, 2014,30(12):e349-e361.
[14] 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]. J Endod, 2017,43(2):257-262.
pmid: 28041686
[15] Shrestha S, Torneck CD, Kishen A. Dentin conditioning with bioactive molecule releasing nanoparticle system enhances adherence, viability, and diffe-rentiation of stem cells from apical papilla[J]. J Endod, 2016,42(5):717-723.
[16] Shrestha S, Diogenes A, Kishen A. Temporal-controlled dexamethasone releasing chitosan nanoparticle system enhances odontogenic differentiation of stem cells from apical papilla[J]. J Endod, 2015,41(8):1253-1258.
doi: 10.1016/j.joen.2015.03.024 pmid: 25956605
[17] Park SJ, Li ZZ, Hwang IN, et al. Glycol chitin-based thermoresponsive hydrogel scaffold supplemented with enamel matrix derivative promotes odontogenic differentiation of human dental pulp cells[J]. J Endod, 2013,39(8):1001-1007.
pmid: 23880267
[18] Palma PJ, Ramos JC, Martins JB, et al. Histologic evaluation of regenerative endodontic procedures with the use of chitosan scaffolds in immature dog teeth with apical periodontitis[J]. J Endod, 2017,43(8):1279-1287.
doi: 10.1016/j.joen.2017.03.005 pmid: 28577961
[19] Asghari Sana F, Çapkın Yurtsever M, Kaynak Bayrak G, et al. Spreading, proliferation and differentiation of human dental pulp stem cells on chitosan scaffolds immobilized with RGD or fibronectin[J]. Cytotechnology, 2017,69(4):617-630.
pmid: 28653139
[20] Amir LR, Suniarti DF, Utami S, et al. Chitosan as a potential osteogenic factor compared with dexamethasone in cultured macaque dental pulp stromal cells[J]. Cell Tissue Res, 2014,358(2):407-415.
doi: 10.1007/s00441-014-1938-1 pmid: 24992928
[21] Kim NR, Lee DH, Chung PH, et al. Distinct diffe-rentiation properties of human dental pulp cells on collagen, gelatin, and chitosan scaffolds[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2009,108(5):e94-e100.
doi: 10.1016/j.tripleo.2009.07.031 pmid: 19836718
[22] Liu M, Zeng X, Ma C, et al. Injectable hydrogels for cartilage and bone tissue engineering[J]. Bone Res, 2017,5:17014.
doi: 10.1038/boneres.2017.14 pmid: 28584674
[23] Bhattacharya M, Malinen MM, Lauren P, et al. Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture[J]. J Control Release, 2012,164(3):291-298.
doi: 10.1016/j.jconrel.2012.06.039 pmid: 22776290
[24] Teti G, Salvatore V, Focaroli S, et al. In vitro osteogenic and odontogenic differentiation of human dental pulp stem cells seeded on carboxymethyl cellulose-hydroxyapatite hybrid hydrogel[J]. Front Phy-siol, 2015,6:297.
[25] Rowley JA, Madlambayan G, Mooney DJ. Alginate hydrogels as synthetic extracellular matrix materials[J]. Biomaterials, 1999,20(1):45-53.
doi: 10.1016/s0142-9612(98)00107-0 pmid: 9916770
[26] Bhoj M, Zhang CF, Green DW. A first step in de novo synjournal of a living pulp tissue replacement u-sing dental pulp MSCs and tissue growth factors, encapsulated within a bioinspired alginate hydrogel[J]. J Endod, 2015,41(7):1100-1107.
pmid: 25958179
[27] Diekjürgen D, Grainger DW. Polysaccharide matrices used in 3D in vitro cell culture systems[J]. Biomaterials, 2017,141:96-115.
doi: 10.1016/j.biomaterials.2017.06.020 pmid: 28672214
[28] Galler KM, Cavender AC, Koeklue U, et al. Bioengineering of dental stem cells in a PEGylated fibrin gel[J]. Regen Med, 2011,6(2):191-200.
doi: 10.2217/rme.11.3 pmid: 21391853
[29] Galler KM, D,Souza RN, Hartgerink JD, et al. Scaffolds for dental pulp tissue engineering[J]. Adv Dent Res, 2011,23(3):333-339.
pmid: 21677088
[30] Segers VF, Lee RT. Local delivery of proteins and the use of self-assembling peptides[J]. Drug Discov Today, 2007,12(13/14):561-568.
[31] Aulisa L, Dong H, Hartgerink JD. Self-assembly of multidomain peptides: sequence variation allows control over cross-linking and viscoelasticity[J]. Bioma-cromolecules, 2009,10(9):2694-2698.
[32] Galler KM, Cavender A, Yuwono V, et al. Self-assembling peptide amphiphile nanofibers as a scaffold for dental stem cells[J]. Tissue Eng Part A, 2008,14(12):2051-2058.
[33] Galler KM, Hartgerink JD, Cavender AC, et al. A customized self-assembling peptide hydrogel for dental pulp tissue engineering[J]. Tissue Eng Part A, 2012,18(1/2):176-184.
[34] Dissanayaka WL, Hargreaves KM, Jin LJ, et al. The interplay of dental pulp stem cells and endothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo[J]. Tissue Eng Part A, 2015,21(3/4):550-563.
[35] Ahmed EM. Hydrogel: preparation, characterization, and applications: a review[J]. J Adv Res, 2015,6(2):105-121.
[36] Gillette BM, Jensen JA, Wang MX, et al. Dynamic hydrogels: switching of 3D microenvironments u-sing two-component naturally derived extracellular matrices[J]. Adv Mater, 2010,22(6):686-691.
doi: 10.1002/adma.200902265 pmid: 20217770
[37] Devillard R, Rémy M, Kalisky J, et al. In vitro assessment of a collagen/alginate composite scaffold for regenerative endodontics[J]. Int Endod J, 2017,50(1):48-57.
doi: 10.1111/iej.2017.50.issue-1 pmid: 26650723
[38] Ravindran S, Zhang YB, Huang CC, et al. Odontogenic induction of dental stem cells by extracellular matrix-inspired three-dimensional scaffold[J]. Tissue Eng Part A, 2014,20(1/2):92-102.
doi: 10.1089/ten.tea.2013.0192
[39] Jones TD, Kefi A, Sun S, et al. An optimized injec-table hydrogel scaffold supports human dental pulp stem cell viability and spreading[J]. Adv Med, 2016,2016:7363579.
doi: 10.1155/2016/7363579 pmid: 27294191
[40] Naghizadeh Z, Karkhaneh A, Khojasteh A. Self-crosslinking effect of chitosan and gelatin on alginate based hydrogels: injectable in situ forming scaffolds[J]. Mater Sci Eng C Mater Biol Appl, 2018,89:256-264.
doi: 10.1016/j.msec.2018.04.018 pmid: 29752097
[41] Khayat A, Monteiro N, Smith EE, et al. GelMA-encapsulated hDPSCs and HUVECs for dental pulp regeneration[J]. J Dent Res, 2017,96(2):192-199.
doi: 10.1177/0022034516682005 pmid: 28106508
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[9] . [J]. Foreign Med Sci: Stomatol, 2005, 32(06): 452 -454 .
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