AccScience Publishing / OR / Online First / DOI: 10.36922/OR026150023
Cite this article
6
Download
112
Views
Related Info Links
More by Authors Links
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
REVIEW ARTICLE

Advances in hydrogels with biomimetic mechanical properties for dental and periodontal tissue engineering and organoid applications

Wenting Lu1† Sucheol Shin2† Ao Zheng1 Shuaiting Wu3 Jinling Liu1 Zhuoyuan Li3 Xiao Wang4* Lingyan Cao1*
Show Less
1 Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai , China
2 School of Chemistry and Energy, Sungshin Women’s University, Seoul , Republic of Korea
3 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai , China
4 Department of Oral Implantology, Shanghai Stomatological Hospital, Fudan University, Shanghai , China
†These authors contributed equally to this work.
Received: 10 April 2026 | Revised: 12 July 2026 | Accepted: 3 August 2026 | Published online: 8 September 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Mechanically biomimetic hydrogels have emerged as promising extracellular matrix-mimicking platforms for dental and periodontal tissue engineering because of their capacity to reproduce the mechanical, structural, and biochemical characteristics of native tissue microenvironments. By providing controllable matrix stiffness, viscoelasticity, stress relaxation, fluid shear stress, and three-dimensional topographical cues, these materials can regulate stem cell fate, coordinate epithelial–mesenchymal interactions, guide tissue morphogenesis, and promote the functional maturation and mineralization of regenerating tissues. This review summarizes recent advances in the design and application of mechanically biomimetic hydrogels for the regeneration of dentin–pulp complexes, tooth germs, periodontal ligament, alveolar bone, and other craniofacial tissues, with particular emphasis on their emerging applications in dental and periodontal organoid engineering. Key material and design parameters, including biomimetic mineralization, mechanical tunability, three-dimensional architectural organization, and dynamic crosslinking, are systematically discussed. The mechanotransductive mechanisms by which hydrogel-derived cues regulate odontogenic, osteogenic, and periodontal differentiation are further examined. In addition, advanced fabrication strategies, including microfluidics, photocrosslinking, three-dimensional bioprinting, and decellularized extracellular matrix-based composites, are reviewed in relation to multicellular organization, vascular network formation, and reconstruction of tissue-specific interfaces. Despite substantial progress, challenges remain, including the attenuation of mechanical signals during long-term culture, insufficient spatiotemporal control of multicellular organization, limited vascularization and innervation, and discrepancies between engineered mineralized tissues and native dental hard tissues. Future developments in intelligent mechanoresponsive hydrogels, high-resolution developmental mechanobiological atlases, organoid-based multiscale validation systems, and automated biomanufacturing may facilitate the transition from empirical tissue repair toward mechanically programmed dental and periodontal regeneration.

Graphical abstract
Keywords
Hydrogel
Organoid
Dental tissue
Mechanical responsiveness
Tissue regeneration
Funding
This work was supported by the National Natural Science Foundation of China (grant numbers: 82270953 and 82401063).
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Wen B, Dai Y, Han X, et al. Biomineralization-inspired mineralized hydrogel promotes the repair and regeneration of dentin/bone hard tissue. npj Regen Med. 2023;8(1):11. doi: 10.1038/s41536-023-00286-3
  2. Mina M, Kollar EJ. The induction of odontogenesis in non-dental mesenchyme combined with early murine mandibular arch epithelium. Arch Oral Biol. 1987;32(2):123-127. doi: 10.1016/0003-9969(87)90055-0
  3. Kollar EJ, Baird GR. Tissue interactions in embryonic mouse tooth germs. II. The inductive role of the dental papilla. J Embryol Exp Morphol. 1970;24(1):173-186.
  4. Thesleff I, Sharpe P. Signalling networks regulating dental development. Mech Dev. 1997;67(2):111-123. doi: 10.1016/S0925-4773(97)00115-9
  5. Zhong C, Wang S, Yan K, Zhao Y, Yang H, Yu J. Integrating organoids and organ-on-a-chip in dental research. Biomaterials. 2026;330:124065. doi: 10.1016/j.biomaterials.2026.124065
  6. Wang J, Li Q, Lin X, et al. LAMB3 regulates extracellular matrix stiffness and promotes odontoblast differentiation in dental papilla. Chem Eng J. 2025;518:164595. doi: 10.1016/j.cej.2025.164595
  7. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126(4):677-689. doi: 10.1016/j.cell.2006.06.044
  8. Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells. Science. 2009;324(5935):1673-1677. doi: 10.1126/science.1171643
  9. Liu N, Zhou M, Zhang Q, et al. Stiffness regulates the proliferation and osteogenic/odontogenic differentiation of human dental pulp stem cells via the WNT signalling pathway. Cell Prolif. 2018;51(2):e12435. doi: 10.1111/cpr.12435
  10. Zhang X, Contessi Negrini N, Correia R, Sharpe PT, Celiz AD, Angelova Volponi A. Generating tooth organoids using defined bioorthogonally cross-linked hydrogels. ACS Macro Lett. 2024;13(12):1620-1626. doi: 10.1021/acsmacrolett.4c00520
  11. Hemeryck L, Hermans F, Chappell J, et al. Organoids from human tooth showing epithelial stemness phenotype and differentiation potential. Cell Mol Life Sci. 2022;79(3):153. doi: 10.1007/s00018-022-04183-8
  12. Hermans F, Hemeryck L, Bueds C, et al. Organoids from mouse molar and incisor as new tools to study tooth-specific biology and development. Stem Cell Rep. 2023;18(5):1166-1181. doi: 10.1016/j.stemcr.2023.03.011
  13. Han B, Cao C, Wang A, et al. Injectable Double-Network Hydrogel-Based Three-Dimensional Cell Culture Systems for Regenerating Dental Pulp. ACS Appl Mater Interfaces. 2023;15(6):7821-7832. doi: 10.1021/acsami.2c20848
  14. Zhang Z, Li C, Guo J, et al. “Young-Mechanical Niche” biomimetic hydrogel promotes dental pulp regeneration through YAP-dependent mechanotransduction. Chem Eng J. 2024;501:157483. doi: 10.1016/j.cej.2024.157483
  15. Xu X, Li Z, Ai X, Tang Y, Yang D, Dou L. Human three-dimensional dental pulp organoid model for toxicity screening of dental materials on dental pulp cells and tissue. Int Endod J. 2022;55(1):79-88. doi: 10.1111/iej.13641
  16. Zhang JJ, Li X, Tian Y, et al. Harnessing Mechanical Stress with Viscoelastic Biomaterials for Periodontal Ligament Regeneration. Adv Sci. 2024;11(18):e2309562. doi: 10.1002/advs.202309562
  17. Gao B, Yao J, Wang Y, et al. Periodontal ligament stem cells-loaded photocrosslinking GelMA/PEGDA scaffolds for periodontal bone regeneration. BMC Biotechnol. 2026;26(1):56. doi: 10.1186/s12896-026-01127-z
  18. Li X, Xia Y, Wang Z, et al. Three-dimensional matrix stiffness-based stem cell soil: Tri-phase biomechanical structure promoted human dental pulp stem cells to achieve pulpodentin regeneration. Mater Today Bio. 2025;31:101591. doi: 10.1016/j.mtbio.2025.101591
  19. Zhang R, Shen Z, Zhao Z, et al. Integrated multi-omics profiling characterizes the crucial role of human dental epithelium during tooth development. Cell Rep. 2025;44(4):115437. doi: 10.1016/j.celrep.2025.115437
  20. Huang Y, Zhao Z, Yang Y, et al. Synergistic peptide-organic matrix enhances mineralization of biomimetic scaffolds for bone regeneration. Mater Horiz. 2025;12(20):8631-8653. doi: 10.1039/d5mh00969c
  21. Kim HY, Cooley V, Kim EJ, et al. Adult dental epithelial stem cell-derived organoids deposit hydroxylapatite biomineral. Int J Oral Sci. 2023;15(1):55. doi: 10.1038/s41368-023-00257-w
  22. Jeong SY, Lee S, Choi WH, Jee JH, Kim HR, Yoo J. Fabrication of dentin-pulp-like organoids using dental-pulp stem cells. Cells. 2020;9(3):642. doi: 10.3390/cells9030642
  23. Zhang C, Shen Y, Huang M, et al. Dynamic hydrogel mechanics in organoid engineering: From matrix design to translational paradigms. Bioact Mater. 2026;55:144-170. doi: 10.1016/j.bioactmat.2025.09.021
  24. Yilmaz-Dagdeviren HD, Arslan YE. Beyond traditional dentistry: How organoids and next-gen hydrogels are redesigning dental tissue regeneration. Biomater Adv. 2026;179:214494. doi: 10.1016/j.bioadv.2025.214494
  25. Luo P, Cheng Y, Luo Y, et al. Hydrogel enhanced organoid multidirectional differentiation via Yap/Tead4 mechanotransduction for accelerated tissue regeneration. ACS Appl Mater Interfaces. 2025;17(26):37601-37616. doi: 10.1021/acsami.5c06161
  26. Shi S, Qiu J, Fu Z, et al. Dynamic hydrogels with independently tunable stress relaxation for stem cell fate regulation and regenerative engineering. Sci China Mater. 2026:1-14. doi: 10.1007/s40843-025-3749-3
  27. Liang C, Wu S, Huang Z, et al. Harnessing Oxidized Alginate Microgels for Rapid and Self-Assembling Dental Tissue Organogenesis In Vitro and In Vivo. Small Sci. 2025;5(12):e202500053. doi: 10.1002/smsc.202500053
  28. Peng YH, Hsiao SK, Gupta K, et al. Dynamic matrices with DNA-encoded viscoelasticity for cell and organoid culture. Nat Nanotechnol. 2023;18(12):1463-1473. doi: 10.1038/s41565-023-01483-3
  29. Elnawam H, Thabet A, Mobarak A, Abdallah A, Elbackly R. Preparation and characterization of bovine dental pulp-derived extracellular matrix hydrogel for regenerative endodontic applications: an in vitro study. BMC Oral Health. 2024;24(1):1281.doi: 10.1186/s12903-024-05004-z
  30. Nugraheni VI, Asrianti Bagio D, Margono A, Julianto I. The Effect of Hydrogel Hyaluronic Acid on Dentine Sialophosphoprotein Expression of Human Dental Pulp Stem Cells. Eur Endod J. 2023;8(4):280-285. doi: 10.14744/eej.2023.59672
  31. 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. doi: 10.3390/ijms242417483
  32. Zhang Y, Ding N, Zhang T, Sun Q, Han B, Yu T. A tetra-PEG hydrogel based aspirin sustained release system exerts beneficial effects on periodontal ligament stem cells mediated bone regeneration. Front Chem. 2019;7:682. doi: 10.3389/fchem.2019.00682
  33. Cui J, Xu R, Dong W, Kaneko T, Chen M, Shi D. Skin-inspired patterned hydrogel with strain-stiffening capability for strain sensors. ACS Appl Mater Interfaces. 2023;15(41):48736-48743. doi: 10.1021/acsami.3c12127
  34. Cordiale A, Stanco D, Visone R, et al. An innovative “tooth-on-chip” microfluidic device emulating the structure and physiology of the dental pulp tissue. Adv Healthc Mater. 2026;15(1):e2502080. doi: 10.1002/adhm.202502080
  35. Ha M, Athirasala A, Tahayeri A, Menezes PP, Bertassoni LE. Micropatterned hydrogels and cell alignment enhance the odontogenic potential of stem cells from apical papilla in-vitro. Dent Mater. 2020;36(1):88-96. doi: 10.1016/j.dental.2019.10.013
  36. Kilic Bektas C, Zhang W, Mao Y, Wu X, Kohn J, Yelick PC. Self-assembled hydrogel microparticle-based tooth-germ organoids. Bioengineering. 2022;9(5):215.doi: 10.3390/bioengineering9050215
  37. Carvalho LAM, Stuani VT, Silva ISPD, et al. Hydrogel microarchitecture as a regulatory cue for in vitro odontogenic differentiation. J Appl Oral Sci. 2026;34:e20250607. doi: 10.1590/1678-7765-2025-0607
  38. Bai M, Zhang Z, Chen H, Liu X, Xie J. Paxillin tunes the relationship between cell-matrix and cell-cell adhesions to regulate stiffness-dependent dentinogenesis. Regen Biomater. 2022;10:rbac100. doi: 10.1093/rb/rbac100
  39. Pankajakshan D, Voytik-Harbin SL, Nör JE, Bottino MC. Injectable highly tunable oligomeric collagen matrices for dental tissue regeneration. ACS Appl Bio Mater. 2020;3(2):859-868. doi: 10.1021/acsabm.9b00944
  40. Lwin HY, Tiskratok W, Kyawsoewin M, et al. Shear Stress Regulates Osteogenic Differentiation of Human Dental Pulp Stem Cells via the p38 Pathway. Int J Mol Sci. 2025;26(12):5667. doi: 10.3390/ijms261256678
  41. Wang X, Dong S, Dong Q, Sun X. Piezo1 Promotes Odontogenic Differentiation of Dental Pulp Stem Cells Under Stress Conditions. Int Dent J. 2025;75(3):1885-1896. doi: 10.1016/j.identj.2025.01.018
  42. Dong J, Li R, Chen Y, Zhu G, Liang X. Mechanosensitive Piezo channels in mineralized tissues: emerging roles in osteodental adaptation and disease. Front Cell Dev Biol. 2025;13:1607337. doi: 10.3389/fcell.2025.1607337
  43. Xu X, Guo Y, Liu P, et al. Piezo Mediates the Mechanosensation and Injury-Repair of Pulpo-Dentinal Complex. Int Dent J. 2024;74(1):71-80. doi: 10.1016/j.identj.2023.07.002
  44. Holland EN, Fernández-Yagüe MA, Zhou DW, et al. FAK, vinculin, and talin control mechanosensitive YAP nuclear localization. Biomaterials. 2024;308:122542. doi: 10.1016/j.biomaterials.2024.122542
  45. Hassan N, Greve B, Götte M. The role of ECM mechanics in cancer mechanotransduction through unraveling the molecular machinery of integrins, FAK, and YAP signaling. Cell Mol Biol Lett. 2026;31(1):86. doi: 10.1186/s11658-026-00905-z
  46. Rosowski J, Bräunig J, Amler AK, Strietzel FP, Lauster R, Rosowski M. Emulating the early phases of human tooth development in vitro. Sci Rep. 2019;9(1):7057. doi: 10.1038/s41598-019-43468-0
  47. Kim GH, Park YD, Lee SY, et al. Odontogenic stimulation of human dental pulp cells with bioactive nanocomposite fiber. J Biomate Appl. 2015;29(6):854-866. doi: 10.1177/0885328214546884
  48. Pierfelice TV, D’Amico E, Petrini M, et al. A Systematic Review on Organ-on-a-Chip in PDMS or Hydrogel in Dentistry: An Update of the Literature. Gels. 2024;10(2):102. doi: 10.3390/gels10020102
  49. Phan TV, Pimpakan T, Suwanchaikasem P, et al. Decellularized matrix-hyaluronic acid-alginate hybrid hydrogels to enable a multi-layered full-thickness oral mucosa-on-a-chip. J Dent. 2025;163:106115. doi: 10.1016/j.jdent.2025.106115
  50. Liang X, Xie L, Zhang Q, et al. Gelatin methacryloyl-alginate core-shell microcapsules as efficient delivery platforms for prevascularized microtissues in endodontic regeneration. Acta Biomater. 2022;144:242-257. doi: 10.1016/j.actbio.2022.03.045
  51. Qian Y, Gong J, Lu K, et al. DLP printed hDPSC-loaded GelMA microsphere regenerates dental pulp and repairs spinal cord. Biomaterials. 2023;299:122137. doi: 10.1016/j.biomaterials.2023.122137
  52. Cunha D, Souza N, Moreira M, et al. 3D-printed microgels supplemented with dentin matrix molecules as a novel biomaterial for direct pulp capping. Clin Oral Investig. 2023;27(3):1215-1225. doi: 10.1007/s00784-022-04735-z
  53. Chen J, Gui X, Qiu T, et al. DLP 3D printing of high-resolution root scaffold with bionic bioactivity and biomechanics for personalized bio-root regeneration. Biomater Adv. 2023;151:213475. doi: 10.1016/j.bioadv.2023.213475
  54. Zhu S, Liao X, Xu Y, et al. 3D bioprinting of high-performance hydrogel with in-situ birth of stem cell spheroids. Bioact Mater. 2024;43:392-405. doi: 10.1016/j.bioactmat.2024.09.033
  55. Jackson A, Bektas C, Mao Y. Optimization of gelatin-based cell carriers for tooth-germ organoids. Global Transl Med. 2025;4(1):67-79. doi: 10.36922/gtm.5897
  56. Yang Y, Zhao J, Qin B, et al. Bioactive photo-crosslinkable hydrogel based on decellularized dental pulp matrix for functional pulp regeneration. BMC Oral Health. 2026;26(1):654. doi: 10.1186/s12903-026-08001-6
  57. Sadeghian A, Kharaziha M, Khoroushi M. Dentin extracellular matrix loaded bioactive glass/GelMA support rapid bone mineralization for potential pulp regeneration. Int J Biol Macromol. 2023;234:123771. doi: 10.1016/j.ijbiomac.2023.123771
  58. Ioannidis K, Dimopoulos A, Decoene I, et al. 4D Biofabrication of Magnetically Augmented Callus Assembloid Implants Enables Rapid Endochondral Ossification via Activation of Mechanosensitive Pathways. Adv Sci. 2025;12(15):e2413680. doi: 10.1002/advs.202413680
  59. Chakraborty J, Fernandez-Perez J, Takhsha Ghahfarokhi M, et al. Development of 4D-bioprinted shape-morphing magnetic constructs for cartilage regeneration using a silk fibroin-gelatin bioink. Cell Rep Phys Sci. 2024;5(3):101819. doi: 10.1016/j.xcrp.2024.101819
  60. Yin Y, Wei Z, Lu B, et al. 4D-printed smart hydrogels in oral medicine: Current applications and future perspectives. J Mech Behav Biomed Mater. 2026;173:107233. doi: 10.1016/j.jmbbm.2025.107233
  61. Menzani B, De Gea P, Gidrol X, Tubbs E. Vascularizing organoids-on-chip for perfused and personalized models. Lab Chip. 2026;26(6):1798-1819. doi: 10.1039/d5lc00890e
  62. Wu Y, Li X, Liu H, et al. Organoids in the oral and maxillofacial region: present and future. Int J Oral Sci. 2024;16(1):61. doi: 10.1038/s41368-024-00324-w
  63. Zhang S, Yu M, Li M, et al. Notch Signaling Hydrogels Enable Rapid Vascularization and Promote Dental Pulp Tissue Regeneration. Adv Sci. 2024;11(35):e2310285. doi: 10.1002/advs.202310285
  64. Wang W, Li J, Zhou Y, et al. EphrinB2 in dental pulp stem cells promotes endothelial cells forming capillary-like cords in a 3D bioprinted hydrogel construct. BMC Mol Cell Biol. 2025;26(1):33. doi: 10.1186/s12860-025-00558-4
  65. Liu J, Li P, Chen Y, et al. Pre-vascularized hydrogel co-encapsulating SHEDs and HUVECs for dental pulp regeneration. Biomater Adv. 2026;180:214539. doi: 10.1016/j.bioadv.2025.214539
  66. Liu F, Xiao J, Chen LH, et al. Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization. World J Stem Cells.2024;16(3):287-304. doi: 10.4252/wjsc.v16.i3.287
  67. Seo EJ, Park JK, Jeong H, Kang JS, Kim HR, Jang IH. Differentiation of CD31-Positive Vascular Endothelial Cells from Organoid Culture of Dental Pulp Stem Cells. Int J Oral Biol. 2018;43(2):77-82. doi: 10.11620/IJOB.2018.43.2.077
  68. Gruenhagen GW, Mubeen T, Patil C, Stockert J, Streelman JT. Single Cell RNA Sequencing Reveals Deep Homology of Dental Cell Types Across Vertebrates. Front Dent Med. 2022;3:845449. doi: 10.3389/fdmed.2022.845449
  69. Al Thamin S, Chiba Y, Yoshizaki K, et al. Transcriptional regulation of the basic helix-loop-helix factor AmeloD during tooth development. J Cell Physiol. 2021;236(11):7533-7543. doi: 10.1002/jcp.30389
  70. Ma X, Ma Y, Lin Z, Ji M. The role of the TGF-β1 signaling pathway in the process of amelogenesis. Front Physiol. 2025;16:1586769. doi: 10.3389/fphys.2025.1586769
  71. de Paiva Narciso N, Christakopoulos F, Huang MS, et al. Tuning viscoelasticity of dynamic covalent hydrogels for human tissue modeling. bioRxiv. Preprint posted online October 17, 2025. doi: 10.1101/2025.10.16.682916
  72. Wu S, Wu X, Wang X, Su J. Hydrogels for bone organoid construction: From a materiobiological perspective. J Mater Sci Technol. 2023;136:21-31. doi: 10.1016/j.jmst.2022.07.008
  73. Dissanayaka WL, Zhu L, Hargreaves KM, Jin L, Zhang C. In vitro analysis of scaffold-free prevascularized microtissue spheroids containing human dental pulp cells and endothelial cells. J Endod. 2015;41(5):663-670. doi: 10.1016/j.joen.2014.12.017
  74. Shi Y, Yu Y, Li J, et al. Spatiotemporal cell landscape of human embryonic tooth development. Cell Prolif. 2024;57(9):e13653. doi: 10.1111/cpr.13653
  75. Huang C, Sanaei F, Verdurmen WPR, Yang F, Ji W, Walboomers XF. The Application of Organs-on-a-Chip in Dental, Oral, and Craniofacial Research. J Dent Res. 2023;102(4):364-375. doi: 10.1177/00220345221145555
  76. Wu X, Yang H, Liu G, et al. Osteomimix: A Multidimensional Biomimetic Cascade Strategy for Bone Defect Repair. Adv Mater. 2025;37(11):e2416715. doi: 10.1002/adma.202416715
  77. Wang X, Yang X, Xiao X, Li X, Chen C, Sun D. Biomimetic design of platelet-rich plasma controlled release bacterial cellulose/hydroxyapatite composite hydrogel for bone tissue engineering. Int J Biol Macromol. 2024;269(Pt 2):132124. doi: 10.1016/j.ijbiomac.2024.132124
  78. Wang Y, Zhang N, Zhang J, Yao R, He J, Wu F. Reinforced enzyme mineralized chitosan hydrogels with superior mechanical and osteogenic properties. Carbohydr Polym. 2025;349(Pt B):123032. doi: 10.1016/j.carbpol.2024.123032
  79. Khetan S, Guvendiren M, Legant WR, Cohen DM, Chen CS, Burdick JA. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat Mater. 2013;12(5):458-465. doi: 10.1038/nmat3586
  80. Cui Z, Liu Z, Zhang Z, et al. On-demand amorphous calcium phosphate-mediated regeneration of dentin and enamel using ion-regulated hydroxypropyl methylcellulose and carboxymethyl chitosan hydrogels. Carbohydr Polym. 2026;381:125170. doi: 10.1016/j.carbpol.2026.125170
  81. Clerkin S, Singh K, Davis JL, et al. Tuneable gelatin methacryloyl (GelMA) hydrogels for the directed specification of renal cell types for hiPSC-derived kidney organoid maturation. Biomaterials. 2025;322:123349. doi: 10.1016/j.biomaterials.2025.123349
  82. Sojdeh S, Panjipour A, Castillo M, Arabpour Z, Djalilian AR. Emerging Smart and Adaptive Hydrogels for Next-Generation Tissue Engineering. Bioengineering. 2025;13(1):50. doi: 10.3390/bioengineering13010050
  83. Liu Z, Fu J, Yuan H, et al. Polyisocyanide hydrogels with tunable nonlinear elasticity mediate liver carcinoma cell functional response. Acta Biomater. 2022;148:152-162. doi: 10.1016/j.actbio.2022.06.022
  84. Ollier RC, Webber MJ. Strain-Stiffening Mechanoresponse in Dynamic-Covalent Cellulose Hydrogels. Biomacromolecules. 2024;25(7):4406-4419. doi: 10.1021/acs.biomac.4c00450
  85. Ohnsorg ML, Mash KM, Khang A, et al. Nonlinear Elastic Bottlebrush Polymer Hydrogels Modulate Actomyosin Mediated Protrusion Formation in Mesenchymal Stromal Cells. Adv Mater. 2024;36(28):e2403198. doi: 10.1002/adma.202403198
  86. Zhang K, Zhou Y, Zhang J, et al. Shape morphing of hydrogels by harnessing enzyme enabled mechanoresponse. Nat Commun. 2024;15(1):249. doi: 10.1038/s41467-023-44607-y
  87. Gross BJ, Soltwedel JR, Shelton E, Gomez C, Campàs O. STRESS, an automated geometrical characterization of deformable particles for in vivo measurements of cell and tissue mechanical stresses. Sci Rep. 2025;15(1):28599. doi: 10.1038/s41598-025-13419-z
  88. Liao L, Feng Q, Xiaofeng X, Cai Z, Xie S. Advances in biomanufacturing and medical applications of three-dimensional-printed organoids: A review. Int J Bioprint. 2025;11(4):66-98. doi: 10.36922/IJB025190184
  89. Cadamuro F, Piazzoni M, Gamba E, et al. Artificial Intelligence tool for prediction of ECM mimics hydrogel formulations via click chemistry. Biomater Adv. 2025;175:214323. doi: 10.1016/j.bioadv.2025.214323
  90. Bai L, Su J. Artificial Intelligence Virtual Organoids (AIVOs). Bioact Mater. 2025;59:45-68. doi: 10.1016/j.bioactmat.2025.12.030
  91. Shi Y, Wang L, Jia H, et al. Artificial intelligence unlocks the future of oral organoid research. Transl Dent Res. 2025;1:100035. doi: 10.1016/j.tdr.2025.100035
  92. Yang J, Fischer NG, Ye Z. Revolutionising oral organoids with artificial intelligence. Biomater Transl. 2024;5(4):372-389. doi: 10.12336/biomatertransl.2024.04.004
  93. Mohammad S, Hossain MS, Sarver SL. Integrating AI with Cellular and Mechanobiology: Trends and Perspectives. Biophysica. 2025;5(4):62. doi: 10.3390/biophysica5040062
  94. Machla F, Monou PK, Artemiou P, et al. Design, additive manufacturing, and characterization of an organ-on-chip microfluidic device for oral mucosa analogue growth. J Mech Behav Biomed Mater. 2025;163:106877. doi: 10.1016/j.jmbbm.2024.106877
  95. Zhang H, Li L, Wang S, Sun X, Luo C, Hou B. Construction of dentin-on-a-chip based on microfluidic technology and tissue engineering. J Dent. 2024;148:105028. doi: 10.1016/j.jdent.2024.105028
  96. Li Y, Huang D, Zhang Y, Xiao Y, Zhang X. Microfluidic-assisted engineering of hydrogels with microscale complexity. Acta Biomater. 2025;199:1-17. doi: 10.1016/j.actbio.2025.05.023
  97. Lai W, Hu G, Xu B, Wang W. Effects of hydrogel stiffness and viscoelasticity on organoid culture: a comprehensive review. Mol Med. 2025;31:83. doi: 10.1186/s10020-025-01131-7
  98. Xiu J, Xue R, Duan X, et al. Mechanical characterization of nonlinear elasticity of growing intestinal organoids with a microinjection method. Acta Biomater. 2025;196:271-280. doi: 10.1016/j.actbio.2025.02.054
  99. Yan J, Ye Z, Lu Y, et al. 3D bioprinting lobule-like hepatorganoids with induced vascularization for orthotopic implantation. Mater Today Bio. 2025;31:101515. doi: 10.1016/j.mtbio.2025.101515
  100. Schot M, Becker M, Paggi CA, et al. Photoannealing of Microtissues Creates High-Density Capillary Network Containing Living Matter in a Volumetric-Independent Manner. Adv Mater. 2024;36(28):e2308949. doi: 10.1002/adma.202308949
  101. Rizzo R, Sampon T, Wilt JK, Stankey PP, Lewis JA. Embedding Perfusable Microchannel Networks in Photoclickable Bioresins via High-Resolution Digital Light Processing. bioRxiv. Preprint posted online October 30, 2025. doi: 10.1101/2025.10.29.685256
  102. Abbasalizadeh S, Babaee S, Kowsari-Esfahan R, et al. Continuous Production of Highly Functional Vascularized Hepatobiliary Organoids from Human Pluripotent Stem Cells using a Scalable Microfluidic Platform. Adv Funct Mater. 2023;33(49):2210233. doi: 10.1002/adfm.202210233
  103. Gusarova E, Ahmadi F, Cruickshank J, et al. A Biomimetic Buffering Hydrogel Scaffold for Long-Term Culture of Patient-Derived Tumor Organoids. Adv Healthc Mater. 2026;15(11):e04669. doi: 10.1002/adhm.202504669
  104. Liang L, Cui R, Zhong S, et al. Analysis of the potential role of photocurable hydrogel in patient-derived glioblastoma organoid culture through RNA sequencing. Biomater Sci. 2022;10(17):4902-4914. doi: 10.1039/d2bm00589a
  105. Li Y, Wang JL, Liang LG. Multiplexed tumor-mimetic dECM-chip platform for colorectal cancer: Interrogating pharmacological synergy and NK cell immunosurveillance dynamics. Talanta. 2026;298:129012. doi: 10.1016/j.talanta.2025.129012
  106. Wimmer RA, Leopoldi A, Aichinger M, et al. Human blood vessel organoids as a model of diabetic vasculopathy. Nature. 2019;565(7740):505-510. doi: 10.1038/s41586-018-0858-8
  107. Pagella P, Jiménez-Rojo L, Mitsiadis TA. Roles of innervation in developing and regenerating orofacial tissues. Cell Mol Life Sci. 2014;71(12):2241-2251. doi: 10.1007/s00018-013-1549-0
  108. Park CH, Rios HF, Jin Q, et al. Tissue engineering bone-ligament complexes using fiber-guiding scaffolds. Biomaterials. 2012;33(1):137-145. doi: 10.1016/j.biomaterials.2011.09.057
  109. Ingber DE. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nature Reviews Genetics. 2022;23(8):467-491. doi: 10.1038/s41576-022-00466-9
  110. Iglesias-Lopez C, Agustí A, Obach M, Vallano A. Regulatory framework for advanced therapy medicinal products in Europe and United States. Front Pharmacol. 2019;10:921. doi: 10.3389/fphar.2019.00921
  111. Detela G, Lodge A. EU regulatory pathways for ATMPs: standard, accelerated and adaptive pathways to marketing authorisation. Mol Ther Methods Clin Dev. 2019;13:205-232. doi: 10.1016/j.omtm.2019.01.012
  112. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials. 2011;32(12):3233-3243. doi: 10.1016/j.biomaterials.2011.01.057
  113. Aamodt JM, Grainger DW. Extracellular matrix-based biomaterial scaffolds and the host response. Biomaterials. 2016;86:68-82. doi: 10.1016/j.biomaterials.2016.02.003
  114. Caliari SR, Burdick JA. A practical guide to hydrogels for cell culture. Nat Methods. 2016;13(5):405-414. doi: 10.1038/nmeth.3839
  115. Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254-271. doi: 10.1016/j.biomaterials.2015.08.045
  116. Madl CM, Heilshorn SC. Engineering hydrogel microenvironments to recapitulate the stem cell niche. Annu Rev Biomed Eng. 2018;20:21-47. doi: 10.1146/annurev-bioeng-062117-120954
  117. Sadtler K, Singh A, Wolf MT, Wang X, Pardoll DM, Elisseeff JH. Design, clinical translation and immunological response of biomaterials in regenerative medicine. Nat Rev Mater. 2016;1:16040. doi: 10.1038/natrevmats.2016.40
  118. Rouwkema J, Khademhosseini A. Vascularization and angiogenesis in tissue engineering: beyond creating static networks. Trends Biotechnol. 2016;34(9):733-745. doi: 10.1016/j.tibtech.2016.03.002
  119. Saberianpour S, Heidarzadeh M, Geranmayeh MH, Hosseinkhani H, Rahbarghazi R, Nouri M. Tissue engineering strategies for the induction of angiogenesis using biomaterials. J Biol Eng. 2018;12:36. doi: 10.1186/s13036-018-0133-4
  120. Beniash E. Biominerals—hierarchical nanocomposites: the example of bone. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2011;3(1):47-69. doi: 10.1002/wnan.105
Share
Back to top
Organoid Research, Electronic ISSN: 3082-8503 Published by AccScience Publishing