Pulp regeneration has been a research hotspot in recent years. Functional pulp regeneration can not be achieved without the cooperation of stem cells, growth factors and biological scaffolds. Stem cells, as undifferentiated mesenchymal cells, have the potential of multi-directional differentiation and are often used as seed cells in pulp regeneration, playing a key role. As a kind of fertile soil for supporting cell growth, bio-scaffolds can provide a three-dimensional culture environment for stem cells and promote cell proliferation and differentiation. Growth factors are more as the stimulation of stem cell proliferation and differentiation of protein molecules, playing an important role. In this paper, the application of odontogenic stem cells, scaffolds and growth factors in pulp regeneration was reviewed.

Cheng Mengke, Yang Dujuan, Liu Jia. Research progress of pulp regeneration based on tissue engineering. Frontiers in Medical Science Research (2024), Vol. 6, Issue 3: 54-60. https://doi.org/10.25236/FMSR.2024.060310.

[1] Lee HN, Liang C, Liao L,et al;. Advances in Research on Stem Cell-Based Pulp Regeneration. Tissue Eng Regen Med. 2021, 18(6):931-940.

[2] Martin-Iglesias S, Milian L, Sancho-Tello M, et al;BMP-2 Enhances Osteogenic Differentiation of Human Adipose-Derived and Dental Pulp Stem Cells in 2D and 3D In Vitro Models. Stem Cells Int. 2022 ,2022:4910399.

[3] Zhang W, Yelick PC.Tooth Repair and Regeneration: Potential of Dental Stem Cells. Trends Mol Med. 2021, 27(5):501-511.

[4] Liu B,Liang JP.Clinical application and future of pulp regeneration[J].Chinese Journal of Stomatology.2020(01):50-55.

[5] Fagalde P, Reininger D.  Oral tissues regeneration using intraoral mesenchymal stem cells. J Clin Exp Dent. 2021, 13(3):e268-e277.

[6] Roato I, Chinigò G, Genova T,et al;Oral Cavity as a Source of Mesenchymal Stem Cells Useful for Regenerative Medicine in Dentistry. Biomedicines. 2021, 9(9):1085.

[7] Yang JW, Shin YY, Seo Y, et al;Therapeutic Functions of Stem Cells from Oral Cavity: An Update. Int J Mol Sci. 2020, 21(12):4389.

[8] Xu K, Xiao J, Zheng K, et al; MiR-21/STAT3 Signal Is Involved in Odontoblast Differentiation of Human Dental Pulp Stem Cells Mediated by TNF-α. Cell Reprogram. 2018, 20(2):107-116.

[9] Cui D, Xiao J, Zhou Y, et al;Epiregulin enhances odontoblastic differentiation of dental pulp stem cells via activating MAPK signalling pathway. Cell Prolif. 2019, 52(6):e12680.

[10] Zhou T, Rong M, Wang Z, et al;Conditioned medium derived from 3D tooth germs: A novel cocktail for stem cell priming and early in vivo pulp regeneration. Cell Prolif. 2021, 54(11):e13129.

[11] Delle Monache S, Martellucci S, Clementi L, et al;In Vitro Conditioning Determines the Capacity of Dental Pulp Stem Cells to Function as Pericyte-Like Cells. Stem Cells Dev. 2019, 28(10):695-706.

[12] Ling L, Zhao YM, Wang XT, et al;Regeneration of Dental Pulp Tissue by Autologous Grafting Stem Cells Derived from Inflammatory Dental Pulp Tissue in Immature Premolars in a Beagle Dog. Chin J Dent Res. 2020,23(2):143-150.

[13] Nazhvani FD, Kazempour S, Hosseini SM, et al;Regeneration of dentin-pulp complex by using dental pulp stem cells in dog. Dent Res J (Isfahan). 2021, 18(1):86.

[14] Hsiao HY, Nien CY, Hong HH, et al;Application of dental stem cells in three-dimensional tissue regeneration. World J Stem Cells. 2021,13(11):1610-1624.

[15] LI Pei, LIN Ling, ZHAO Wei. Research progress of milk tooth pulp stem cells in regenerative repair of oral tissues[J]. International Journal of Stomatology, 2022, 49(04):483-488.

[16] Yuan X, Yuan Z, Wang Y, et al. Vascularized pulp regeneration via injecting simvastatin functionalized GelMA cryogel microspheres loaded with stem cells from human exfoliated deciduous teeth. Mater Today Bio. 2022,13:100209.

[17] Wu M, Liu X, Li Z, et al;SHED aggregate exosomes shuttled miR-26a promote angiogenesis in pulp regeneration via TGF-β/SMAD2/3 signalling. Cell Prolif. 2021,54(7):e13074.

[18] Damrongsri D, Nowwarote N, Sonpoung O,et al;Differential expression of Notch related genes in dental pulp stem cells and stem cells isolated from apical papilla. J Oral Biol Craniofac Res. 2021, 11(3):379-385.

[19] Parthiban SP, He W, Monteiro N, et al;Engineering pericyte-supported microvascular capillaries in cell-laden hydrogels using stem cells from the bone marrow, dental pulp and dental apical papilla. Sci Rep. 2020, 10(1):21579.

[20] Smeda M, Galler KM, Woelflick M, et al. Molecular Biological Comparison of Dental Pulp- and Apical Papilla-Derived Stem Cells. Int J Mol Sci. 2022, 23(5):2615.

[21] Zhang J, Ding H, Liu X, et al;Tissue Engineering and Immunomodulation. Stem Cells Dev. 2019, 28(15):986-994.

[22] Queiroz A, Albuquerque-Souza E, Gasparoni LM, et al. Therapeutic potential of periodontal ligament stem cells. World J Stem Cells. 2021, 13(6):605-618.

[23] Bi R, Lyu P, Song Y, et al.Function of Dental Follicle Progenitor/Stem Cells and Their Potential in Regenerative Medicine: From Mechanisms to Applications. Biomolecules. 2021,11(7):997.

[24] Hong H, Chen X, Li K, et al. Dental follicle stem cells rescue the regenerative capacity of inflamed rat dental pulp through a paracrine pathway. Stem Cell Res Ther. 2020,11(1):333.

[25] Niu Weidong,Liu Runyuan.3D stem cell culture in pulp regeneration research[J]. Oral Medicine Research, 2021,37(11):961-965.

[26] Zhang M, Li C, Zhou LP, et al;Polymer Scaffolds for Biomedical Applications in Peripheral Nerve Reconstruction. Molecules. 2021,26(9):2712.

[27] Carvalho GL, Sarra G, Schröter GT, et al;Pro-angiogenic potential of a functionalized hydrogel scaffold as a secretome delivery platform: An innovative strategy for cell homing-based dental pulp tissue engineering. J Tissue Eng Regen Med. 2022,16(5):472-483.

[28] Moreira MS, Sarra G, Carvalho GL, et al;Physical and Biological Properties of a Chitosan Hydrogel Scaffold Associated to Photobiomodulation Therapy for Dental Pulp Regeneration: An In Vitro and In Vivo Study. Biomed Res Int. 2021,2021:6684667.

[29] Bordini EAF, Cassiano FB, Bronze-Uhle ES, Alamo L, Hebling J, de Souza Costa CA, Soares DG. Chitosan in association with osteogenic factors as a cell-homing platform for dentin regeneration: Analysis in a pulp-in-a-chip model. Dent Mater. 2022,38(4):655-669. 

[30] BAI Lang,HAN Qibin,YANG Xing,et al. Research progress of new hydrogel materials for repairing articular cartilage injury[J]. International Journal of Orthopaedics, 2021, 42(04):221-225.

[31] Ferroni L, Gardin C, Sivolella S, et al;A hyaluronan-based scaffold for the in vitro construction of dental pulp-like tissue. Int J Mol Sci. 2015,16(3):4666-4681.

[32] Silva CR, Babo PS, Gulino M, et al; Injectable and tunable hyaluronic acid hydrogels releasing chemotactic and angiogenic growth factors for endodontic regeneration. Acta Biomater. 2018,77: 155-171.

[33] Choi D, Qiu M, Hwang YC, et al. The Effects of 3-Dimensional Bioprinting Calcium Silicate Cement/Methacrylated Gelatin Scaffold on the Proliferation and Differentiation of Human Dental Pulp Stem Cells. Materials (Basel). 2022,15(6):2170.

[34] Gong Jiaxing. Tissue-engineered pulp reconstruction based on DLP printing technology and its biological performance evaluation[D]. Zhejiang University, 2020.

[35] Yang WX. Preparation and characterization of composite neural scaffolds with extracellular matrix from bionic exfoliated mammary stem cells[D]. China Medical University, 2022.

[36] Hu N, Li W, Jiang W, Wen J, Gu S. Creating a Microenvironment to Give Wings to Dental Pulp Regeneration-Bioactive Scaffolds. Pharmaceutics. 2023,15(1):158. 

[37] Adanir N, Khurshid Z, Ratnayake J. The Regenerative Potential of Decellularized Dental Pulp Extracellular Matrix: A Systematic Review. Materials (Basel). 2022,15(18):6386. 

[38] Yang N. Experimental study on the regeneration of pulp-dentin complex promoted by extracellular matrix scaffolds of pulp-mimicking exfoliated milk tooth stem cells[D]. China Medical University, 2022.

[39] Bakhtiar H, Ashoori A, Rajabi S, Pezeshki-Modaress M, Ayati A, Mousavi MR, Ellini MR, Kamali A, Azarpazhooh A, Kishen A. Human amniotic membrane extracellular matrix scaffold for dental pulp regeneration in vitro and in vivo. Int Endod J. 2022,55(4):374-390.

[40] ZHOU Yi,ZHAO Yuming. Research progress of dental pulp regeneration scaffold materials[J]. International Journal of Stomatology,2022,49(01):19-26.

[41] ZHOU Fangjie,HE Libang,LI Jiyao. Prospects of polylactic acid-hydroxyacetic acid copolymers in the treatment of endodontic diseases[J]. Oral Disease Control, 2021, 29(03):202-205.

[42] Gangolli RA, Devlin SM, Gerstenhaber JA, et al;A Bilayered Poly (Lactic-Co-Glycolic Acid) Scaffold Provides Differential Cues for the Differentiation of Dental Pulp Stem Cells. Tissue Eng Part A. 2019,25(3-4):224-233.

[43] Xie X, Shi X, Wang S, et al;Effect of Attapulgite-Doped Electrospun Fibrous PLGA Scaffold on Pro-Osteogenesis and Barrier Function in the Application of Guided Bone Regeneration. Int J Nanomedicine. 2020,15:6761-6777.

[44] Istikharoh F, Sujuti H, Mustamsir E, et al;Preparation and biodegradable properties of hydroxyapatite nanoparticle composite coated with poly lactic-co-glycolic acid/polyvinyl alcohol for bone regeneration. Dent Med Probl. 2020,57(4):363-367.

[45] Chen RS, Hsu SH, Chang HH, et al;Challenge Tooth Regeneration in Adult Dogs with Dental Pulp Stem Cells on 3D-Printed Hydroxyapatite/Polylactic Acid Scaffolds. Cells. 2021,10(12):3277.

[46] Shibui T, Yajima T, Irie K, et al;Architecture of connective tissue regenerated by enamel matrix derivative around hydroxyapatite implanted into tooth extraction sockets in the rat maxilla. Anat Sci Int. 2020, 95(3):334-341.

[47] Cicciù M. Growth Factor Applied to Oral and Regenerative Surgery. Int J Mol Sci. 2020, 21(20):7752.

[48] Niu Yumei,He Lina. Research progress of dental pulp stem cells in pulp-dentin regeneration[J]. Oral Medicine Research, 2018, 34(09):923-927.

[49] Wu Jiameng. In vivo study on the combination of NELL-1 and BMP2 in the repair of dental cord injury in rats [D]. Shandong University, 2018.

[50] Chang HH, Chen IL, Wang YL, et al. Regulation of the regenerative activity of dental pulp stem cells from exfoliated deciduous teeth (SHED) of children by TGF-β1 is associated with ALK5/Smad2, TAK1, p38 and MEK/ERK signaling. Aging (Albany NY). 2020, 12(21):21253-21272.

[51] Li Caiyu. Study on the effect of FGF2 on the dentinogenic differentiation ability of human deciduous pulp stem cells [D]. Chongqing Medical University, 2020.

[52] Ding T, Kang W, Li J, et al. An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration. J Nanobiotechnology. 2021, 19(1):247. 

[53] Kurogoushi R, Hasegawa T, Akazawa Y, et al. Fibroblast growth factor 2 suppresses the expression of C-C motif chemokine 11 through the c-Jun N-terminal kinase pathway in human dental pulp-derived mesenchymal stem cells. Exp Ther Med. 2021, 22(6):1356.