牙髓再生支架材料的研究进展

doi:10.13591/j.cnki.kqyx.2025.03.011

摘要/Abstract

摘要：

牙髓再生是目前牙髓病学研究的热点课题。随着再生医学的发展,牙髓再生正从基础研究向临床应用转化,并在一些病例中观察到了比较稳定的结果,但实现更高的成功率和恢复牙髓的功能仍然是牙髓病学领域的一个挑战。干细胞、生长因子和支架材料是组织工程的基本要素。近年来牙髓再生相关支架受到广泛关注,无论是天然来源的、人体来源的还是人工合成的支架材料都取得了新的进展。该文就牙髓再生的支架材料进行综述,旨在为牙髓再生支架材料的选择提供参考。

关键词: 牙髓再生, 再生性牙髓治疗, 干细胞, 支架

Abstract:

Pulp regeneration is currently a hot topic in pulp disease research. With the development of regenerative medicine, pulp regeneration is transitioning from basic research to clinical applications, and stable results have been observed in some cases. However, achieving higher success rates and restoring pulp function remains a challenge in the field of pulp disease. Stem cells, growth factors, and scaffold materials are fundamental elements of tissue engineering. In recent years, dental pulp regeneration related scaffolds have received widespread attention, and new progress has been made in natural, human, and artificially synthesized scaffold materials. This article reviews the scaffold materials for pulp regeneration, aiming to provide reference for the selection of scaffold materials for dental pulp regeneration.

Key words: dental pulp regeneration, regenerative endodontic procedures, stem cells, scaffolds

中图分类号:

R781.4

刘塬, 颜燕宏, 蒋备战. 牙髓再生支架材料的研究进展[J]. 口腔医学, 2025, 45(3): 218-222.

LIU Yuan, YAN Yanhong, JIANG Beizhan. Research progress of scaffold materials for dental pulp regeneration[J]. Stomatology, 2025, 45(3): 218-222.

图/表 2

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表2

参考文献 49

[1]	Eramo S, Natali A, Pinna R, et al. Dental pulp regenerationvia cell homing[J]. Int Endod J, 2018, 51(4): 405-419. doi: 10.1111/iej.12868 pmid: 29047120
[2]	Lee C, Song MJ. Failure of regenerative endodontic procedures: Case analysis and subsequent treatment options[J]. J Endod, 2022, 48(9): 1137-1145. doi: 10.1016/j.joen.2022.06.002 pmid: 35714726
[3]	Kobayashi E, Flückiger L, Fujioka-Kobayashi M, et al. Comparative release of growth factors from PRP, PRF, and advanced-PRF[J]. Clin Oral Investig, 2016, 20(9): 2353-2360.
[4]	Arshad S, Tehreem F, Khan MR, et al. Platelet-rich fibrin used in regenerative endodontics and dentistry: Current uses, limitations, and future recommendations for application[J]. Int J Dent, 2021, 2021: 4514598.
[5]	Zhang J, Wu JK, Lin XY, et al. Platelet-rich fibrin promotes the proliferation and osteo-/odontoblastic differentiation of human dental pulp stem cells[J]. Curr Stem Cell Res Ther, 2023, 18(4): 560-567.
[6]	Bakhtiar H, Esmaeili S, Fakhr Tabatabayi S, et al. Second-generation platelet concentrate (platelet-rich fibrin) as a scaffold in regenerative endodontics: A case series[J]. J Endod, 2017, 43(3): 401-408. doi: S0099-2399(16)30743-9 pmid: 28131412
[7]	Simões-Pedro M, Tróia PMBPS, dos Santos NBM, et al. Tensile strength essay comparing three different platelet-rich fibrin membranes (L-PRF, A-PRF, and A-PRF+): A mechanical and structural in vitro evaluation[J]. Polymers, 2022, 14(7): 1392.
[8]	Qiao J, An N, Ouyang XY. Quantification of growth factors in different platelet concentrates[J]. Platelets, 2017, 28(8): 774-778. doi: 10.1080/09537104.2016.1267338 pmid: 28277063
[9]	Zhang ML, Jiang F, Zhang XC, et al. The effects of platelet-derived growth factor-BB on human dental pulp stem cells mediated dentin-pulp complex regeneration[J]. Stem Cells Transl Med, 2017, 6(12): 2126-2134.
[10]	Hong S, Li L, Cai W, et al. The potential application of concentrated growth factor in regenerative endodontics[J]. Int Endod J, 2019, 52(5): 646-655. doi: 10.1111/iej.13045 pmid: 30471228
[11]	Tian SB, Wang J, Dong FS, et al. Concentrated growth factor promotes dental pulp cells proliferation and mineralization and facilitates recovery of dental pulp tissue[J]. Med Sci Monit, 2019, 25: 10016-10028.
[12]	Li ZX, Liu L, Wang L, et al. The effects and potential applications of concentrated growth factor in dentin-pulp complex regeneration[J]. Stem Cell Res Ther, 2021, 12(1): 357.
[13]	Nivedhitha MS, Jacob B, Ranganath A. Concentrated growth factor: A novel platelet concentrate for revascularization of immature permanent teeth—A report of two cases[J]. Case Rep Dent, 2020, 2020: 1329145.
[14]	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[J]. Contemp Clin Dent, 2015, 6(1): 63-68.
[15]	Zhou RH, Wang YM, Chen YM, et al. Radiographic, histologic, and biomechanical evaluation of combined application of platelet-rich fibrin with blood clot in regenerative endodontics[J]. J Endod, 2017, 43(12): 2034-2040.
[16]	Nageh M, Ahmed GM, El-Baz AA. Assessment of regaining pulp sensibility in mature necrotic teeth using a modified revascularization technique with platelet-rich fibrin: A clinical study[J]. J Endod, 2018, 44(10): 1526-1533. doi: S0099-2399(18)30441-2 pmid: 30174103
[17]	Ray HLJr, Marcelino J, Braga R, et al. Long-term follow up of revascularization using platelet-rich fibrin[J]. Dent Traumatol, 2016, 32(1): 80-84. doi: 10.1111/edt.12189 pmid: 26095129
[18]	Hong SB, Chen WT, Jiang BZ. A comparative evaluation of concentrated growth factor and platelet-rich fibrin on the proliferation, migration, and differentiation of human stem cells of the apical papilla[J]. J Endod, 2018, 44(6): 977-983. doi: S0099-2399(18)30168-7 pmid: 29703620
[19]	Xu FF, Qiao L, Zhao YM, et al. The potential application of concentrated growth factor in pulp regeneration: An in vitro and in vivo study[J]. Stem Cell Res Ther, 2019, 10(1): 134.
[20]	Jin RZ, Song GT, Chai JH, et al. Effects of concentrated growth factor on proliferation, migration, and differentiation of human dental pulp stem cells in vitro[J]. J Tissue Eng, 2018, 9: 2041731418817505.
[21]	Laschke MW, Später T, Menger MD. Microvascular fragments: More than just natural vascularization units[J]. Trends Biotechnol, 2021, 39(1): 24-33. doi: 10.1016/j.tibtech.2020.06.001 pmid: 32593437
[22]	Xu X, Liang C, Gao X, et al. Adipose tissue-derived microvascular fragments as vascularization units for dental pulp regeneration[J]. J Endod, 2021, 47(7): 1092-1100. doi: 10.1016/j.joen.2021.04.012 pmid: 33887305
[23]	Li ZH, Wu ML, Liu SY, et al. Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration[J]. Mol Ther, 2022, 30(10): 3193-3208. doi: 10.1016/j.ymthe.2022.05.006 pmid: 35538661
[24]	Zheng JM, Kong YY, Hu XL, et al. MicroRNA-enriched small extracellular vesicles possess odonto-immunomodulatory properties for modulating the immune response of macrophages and promoting odontogenesis[J]. Stem Cell Res Ther, 2020, 11(1): 517.
[25]	Zhang SC, Yang Y, Jia SX, et al. Exosome-like vesicles derived from Hertwig’s epithelial root sheath cells promote the regeneration of dentin-pulp tissue[J]. Theranostics, 2020, 10(13): 5914-5931.
[26]	Poornejad N, Schaumann LB, Buckmiller EM, et al. The impact of decellularization agents on renal tissue extracellular matrix[J]. J Biomater Appl, 2016, 31(4): 521-533. pmid: 27312837
[27]	Liang ZL, Li JD, Lin HK, et al. Understanding the multi-functionality and tissue-specificity of decellularized dental pulp matrix hydrogels for endodontic regeneration[J]. Acta Biomater, 2024, 181: 202-221. doi: 10.1016/j.actbio.2024.04.040 pmid: 38692468
[28]	Melling GE, Colombo JS, Avery SJ, et al. Liposomal delivery of demineralized dentin matrix for dental tissue regeneration[J]. Tissue Eng Part A, 2018, 24(13/14): 1057-1065.
[29]	Guo H, Li B, Wu ML, et al. Odontogenesis-related developmental microenvironment facilitates deciduous dental pulp stem cell aggregates to revitalize an avulsed tooth[J]. Biomaterials, 2021, 279: 121223.
[30]	Ricard-Blum S. The collagen family[J]. Cold Spring Harb Perspect Biol, 2011, 3(1): a004978.
[31]	Yang XC, Han GL, Pang X, et al. Chitosan/collagen scaffold containing bone morphogenetic protein-7 DNA supports dental pulp stem cell differentiation in vitro and in vivo[J]. JBiomedMaterRes A, 2020, 108(12): 2519-2526.
[32]	Liang C, Liang QQ, Xu X, et al. Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis: Therapeutic potential for endogenous pulp regeneration[J]. Int J Oral Sci, 2022, 14(1): 38.
[33]	Yue K, Trujillo-de Santiago G, Alvarez MM, et al. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels[J]. Biomaterials, 2015, 73: 254-271. doi: 10.1016/j.biomaterials.2015.08.045 pmid: 26414409
[34]	Qian Y, Gong JX, Lu KJ, et al. DLP printed hDPSC-loaded GelMA microsphere regenerates dental pulp and repairs spinal cord[J]. Biomaterials, 2023, 299: 122137.
[35]	Zhang RT, Xie L, Wu H, et al. Alginate/laponite hydrogel microspheres co-encapsulating dental pulp stem cells and VEGF for endodontic regeneration[J]. Acta Biomater, 2020, 113: 305-316. doi: S1742-7061(20)30397-4 pmid: 32663663
[36]	Zhang HT, Cheng JQ, Ao Q. Preparation of alginate-based biomaterials and their applications in biomedicine[J]. Mar Drugs, 2021, 19(5): 264.
[37]	Liang X, Xie L, Zhang QY, et al. Gelatin methacryloyl-alginate core-shell microcapsules as efficient delivery platforms for prevascularized microtissues in endodontic regeneration[J]. Acta Biomater, 2022, 144: 242-257. doi: 10.1016/j.actbio.2022.03.045 pmid: 35364321
[38]	Chen H, Fu HC, Wu X, et al. Regeneration of pulpo-dentinal-like complex by a group of unique multipotent CD24a⁺ stem cells[J]. Sci Adv, 2020, 6(15): eaay1514.
[39]	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.
[40]	Silva CR, Babo PS, Gulino M, et al. Injectable and tunable hyaluronic acid hydrogels releasing chemotactic and angiogenic growth factors for endodontic regeneration[J]. Acta Biomater, 2018, 77: 155-171. doi: S1742-7061(18)30429-X pmid: 30031163
[41]	Ducret M, Montembault A, Josse J, et al. Design and characterization of a chitosan-enriched fibrin hydrogel for human dental pulp regeneration[J]. Dent Mater, 2019, 35(4): 523-533. doi: S0109-5641(18)31091-1 pmid: 30712823
[42]	Pothupitiya JU, Zheng C, Saltzman WM. Synthetic biodegradable polyesters for implantable controlled-release devices[J]. Expert Opin Drug Deliv, 2022, 19(10): 1351-1364. doi: 10.1080/17425247.2022.2131768 pmid: 36197839
[43]	Terranova L, Louvrier A, Hébraud A, et al. Highly structured 3D electrospun conical scaffold: A tool for dental pulp regeneration[J]. ACS Biomater Sci Eng, 2021, 7(12): 5775-5787. doi: 10.1021/acsbiomaterials.1c00900 pmid: 34846849
[44]	Soares DG, Zhang ZP, Mohamed F, et al. Simvastatin and nanofibrous poly(l-lactic acid) scaffolds to promote the odontogenic potential of dental pulp cells in an inflammatory environment[J]. Acta Biomater, 2018, 68: 190-203. doi: S1742-7061(17)30803-6 pmid: 29294374
[45]	Chen G, Chen JL, Yang B, et al. Combination of aligned PLGA/Gelatin electrospun sheets, native dental pulp extracellular matrix and treated dentin matrix as substrates for tooth root regeneration[J]. Biomaterials, 2015, 52: 56-70. doi: 10.1016/j.biomaterials.2015.02.011 pmid: 25818413
[46]	Galler KM, Brandl FP, Kirchhof S, et al. Suitability of different natural and synthetic biomaterials for dental pulp tissue engineering[J]. Tissue Eng Part A, 2018, 24(3/4): 234-244.
[47]	Demarco FF, Casagrande L, Zhang ZC, et al. Effects of morphogen and scaffold porogen on the differentiation of dental pulp stem cells[J]. J Endod, 2010, 36(11): 1805-1811. doi: 10.1016/j.joen.2010.08.031 pmid: 20951292
[48]	Itoh Y, Sasaki JI, Hashimoto M, et al. Pulp regeneration by 3-dimensional dental pulp stem cell constructs[J]. J Dent Res, 2018, 97(10): 1137-1143. doi: 10.1177/0022034518772260 pmid: 29702010
[49]	Jiménez-Aristazábal RF, Carmona JU, Prades M. Changes on the structural architecture and growth factor release, and degradation in equine platelet-rich fibrin clots cultured over time[J]. J Equine Vet Sci, 2019, 82: 102789.

参考文献	APC	结果
Narang等^[14]	PRF和PRP	临床研究表明,PRF加速牙髓坏死的未成熟恒牙牙根生长,促进作用优于PRP和血凝块
Zhou等^[15]	PRF	PRF联合血凝块可促进比格犬根尖周愈合,促进牙根发育
Nageh等^[16]	PRF	PRF用于REPs,有助于恢复牙齿感觉
Ray等^[17]	PRF	病例报告证明PRF促进REPs的临床效果
Hong等^[18]	CGF和PRF	CGF和PRF均能促进SCAP的增殖、迁移和分化
Xu等^[19]	CGF	在体内外研究中,CGF以剂量依赖的方式促进暴露于LPS的DPSCs的增殖、迁移和分化,并且显示出抗炎作用
Jin等^[20]	CGF	CGF以剂量依赖的方式促进DPSCs的增殖,但高浓度的CGF抑制DPSCs的内皮细胞向分化和成牙本质细胞向分化

参考文献	种类	修饰方法	负载细胞	结果
Terranova等^[43]	PLA和PCL	单宁酸微粒修饰	DPSCs	单宁酸微粒修饰的薄膜支架模拟了ECM,维持细胞活性。将薄膜卷曲为锥形结构促进了细胞迁移。
Soares等^[44]	PLA	将辛伐他汀和纳米纤维偶联支架	牙髓细胞	支架材料减轻了局部炎症,诱导DPSCs产生血管化的牙髓组织。
Chen等^[45]	PLGA	明胶改性支架	牙囊干细胞	通过电纺排列的PLGA/明胶膜片促进了牙囊干细胞的分化,产生牙髓牙本质复合体样结构。
Galler等^[46]	比较PEG、SAP、纤维蛋白和胶原		DPSCs	与PEG和SAP支架相比,天然材料,尤其是纤维蛋白,在细胞活力和牙髓组织形成方面更具优势。
Demarco等^[47]	PLA	模拟牙本质的多孔结构	DPSCs	模拟牙本质的形态可以影响DPSCs的行为,并诱导细胞分化产生牙髓组织。
Itoh等^[48]	聚(N-异丙基丙烯酰胺)	热响应的水凝胶支架	DPSCs	热响应水凝胶在体内实验形成血管化的牙髓组织。