AccScience Publishing / IJB / Volume 12 / Issue 4 / DOI: 10.36922/IJB026050038
Submit to IJB
Cite this article
25
Download
352
Views
Related Info Links
Google Scholar
More by Authors Links
Stefania Sabella
Sailing He
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW ARTICLE

Multiscale 3D printing in tissue engineering: From micro/nanoscale precision to functional organoid fabrication

Zewei He1,2† ,  Guolong Zhang1,3† ,  Saverio Caporalini4† ,  Julian Evans1 ,  Pengfei Yi5 ,  Stefania Sabella4,6* ,  Sailing He1,7*
Show Less
1 Center for Optical and Electromagnetic Research, National Engineering Research Center for Optical Instruments, Zhejiang University, Hangzhou, Zhejiang , China
2 Qianyuan Laboratory, Hangzhou, Zhejiang , China
3 The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, Zhejiang , China
4 Nanoregulatory Group, Translational Pharmacology Facility, Italian Institute of Technology , Genoa, Liguria , Italy
5 School of Computer Science and Technology, College of Mathematical Medicine, Zhejiang Normal University, Jinhua, Zhejiang , China
6 School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang , China
7 Department of Electromagnetic Engineering, School of Electrical Engineering, Royal Institute of Technology (KTH), Stockholm , Sweden
†These authors contributed equally to this work.
IJB 2026, 12(4), 026050038 https://doi.org/10.36922/IJB026050038
Received: 29 January 2026 | Revised: 23 March 2026 | Accepted: 27 March 2026 | Published online: 14 August 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/ )
Download PDF
XML
Cite
Abstract

Three-dimensional (3D) biofabrication is increasingly used in tissue engineering and regenerative medicine to recreate the spatial, mechanical, and biochemical complexity of native cellular microenvironments. Among light-based 3D printing technologies, volumetric bioprinting (VBP) and two-photon polymerization (TPP) offer complementary capabilities across distinct length scales. This review examines their evolution, key advances, and potential integration within a multiscale biofabrication framework. VBP enables rapid, layer-free fabrication of centimeter-scale, cell-laden constructs by delivering spatially modulated light doses throughout a photosensitive volume. This approach reduces mechanical stress, supports high cell viability, and permits complex internal architectures, including perfusable vascular networks. Advances in computed axial lithography, holographic patterning, and bioink engineering are reviewed, with emphasis on optical transparency, control of light scattering, and rheological stability in cell-dense systems. TPP, by contrast, uses nonlinear optical confinement to achieve submicrometer resolution and precise 3D control over scaffold architecture, mechanics, and biochemical patterning. These capabilities support deterministic regulation of cell–material interactions and applications in stem cell niche engineering, neural and vascular interface design, tumor microenvironment modeling, and biohybrid microsystems. Integrating VBP and TPP may bridge organ-scale architecture and perfusion with microscale niche definition and molecular-level signaling, thereby supporting the development of functional organoids and living tissues and better addressing distinct but interdependent biological requirements across organ, tissue, cellular, and molecular scales. Remaining challenges include material heterogeneity, optical–biological coupling, scalability, and long-term tissue maturation. Future progress will require coordinated advances in materials, optical design, computational modeling, and predictive design strategies to enable the translational biofabrication of functional living systems.

Graphical abstract
Keywords
3D printing
Two-photon polymerization
Biofabrication
Volumetric bioprinting
Organogenesis
Functional organoids
Funding
This work was supported by “Pioneer” and “Leading Goose” R&D Program of Zhejiang Province (Nos. 2025C02159, 2024C03045), The National Natural Science Foundation of China (No. W2412107), Zhejiang Provincial Health Commission (No. CXTD202502029), Ningbo Public Welfare Research Program Project (No. 2024Z234), and NanoKeySens project, funded by Italian Workers Health, Safety, and Insurance Authority (INAIL) Italy (No. EPTR0018).
Conflict of interest
The authors declare they have no competing interests.
References
  1. Arias-Peregrino VM, Tenorio-Barajas AY, Mendoza-Barrera CO, et al. 3D printing for tissue engineering: printing techniques, biomaterials, challenges, and the emerging role of 4D bioprinting. Bioengineering (Basel). 2025;12(9):936. doi: 10.3390/bioengineering12090936
  2. Ashworth JC, Cox TR. The importance of 3D fibre architecture in cancer and implications for biomaterial model design. Nat Rev Cancer. 2024;24:461-479. doi: 10.1038/s41568-024-00704-8
  3. Burdis R, Kelly DJ. Biofabrication and bioprinting using cellular aggregates, microtissues and organoids for the engineering of musculoskeletal tissues. Acta Biomater. 2021;126:1-14. doi: 10.1016/j.actbio.2021.03.016
  4. Karvinen J, Kellomäki M. Design aspects and characterization of hydrogel-based bioinks for extrusion-based bioprinting. Bioprinting. 2023;32:e00274. doi: 10.1016/j.bprint.2023.e00274
  5. Maturavongsadit P, Narayanan LK, Chansoria P, Shirwaiker R, Benhabbour SR. Cell-laden nanocellulose/chitosan-based bioinks for 3D bioprinting and enhanced osteogenic cell differentiation. ACS Appl Bio Mater. 2021;4:2342-2353. doi: 10.1021/acsabm.0c01108
  6. Miri AK, Khalilpour A, Cecen B, et al. Multiscale bioprinting of vascularized models. Biomaterials. 2019;198:204-216. doi: 10.1016/j.biomaterials.2018.08.006
  7. Dehghani F, Annabi N. Engineering porous scaffolds using gas-based techniques. Curr Opin Biotechnol. 2011;22(5):661-666. doi: 10.1016/j.copbio.2011.04.005
  8. Chausse V, Casanova-Batlle E, Canal C, et al. Solvent-cast direct-writing and electrospinning as a dual fabrication strategy for drug-eluting polymeric bioresorbable stents. Addit Manuf. 2023;71:103568. doi: 10.1016/j.addma.2023.103568
  9. Zhang J, Byers P, Erben A, et al. Single cell bioprinting with ultrashort laser pulses. Adv Funct Mater. 2021;31:2100066. doi: 10.1002/adfm.202100066
  10. Zhang X, Zhang K, Zhang L, Wang W, Li Y, He R. Additive manufacturing of cellular ceramic structures: from structure to structure–function integration. Mater Des. 2022;215:110470. doi: 10.1016/j.matdes.2022.110470
  11. Liu J, Wang Q, Xu K, et al. AI-enhanced magnetically controlled 4D printing: reshaping the future of medical robotics. Int J Bioprint. 2025;11(6):197-204. doi: 10.36922/IJB025420427
  12. Hongjin W, Han C, Baoxiang J, Shiqi Y, Xiaoyu X. Reconstituting neurovascular unit based on the close relations between neural stem cells and endothelial cells: an effective method to explore neurogenesis and angiogenesis. Rev Neurosci. 2020;31(2):143-159. doi: 10.1515/revneuro-2019-0023
  13. Dou XQ, Feng CL. Amino acids and peptide-based supramolecular hydrogels for three-dimensional cell culture. Adv Mater. 2017;29(16):1604062. doi: 10.1002/adma.201604062
  14. Kawata S, Sun HB, Tanaka T, et al. Finer features for functional microdevices. Nature. 2001;412:697-698. doi: 10.1038/35089130
  15. Zhao CX, Liu JN, Li BQ, et al. Multiscale construction of bifunctional electrocatalysts for long-lifespan rechargeable zinc–air batteries. Adv Funct Mater. 2020;30(36):2003619. doi: 10.1002/adfm.202003619
  16. O'Halloran S, Pandit A, Heise A, et al. Two-photon polymerization: fundamentals, materials, and chemical modification strategies. Adv Sci (Weinh). 2023;10(7):2204072. doi: 10.1002/advs.202204072
  17. Wang W, Chen Z, Lin B, et al. Two-photon polymerization-based 3D micro-scaffolds toward biomedical devices. Chem Eng J. 2024;493:152469. doi: 10.1016/j.cej.2024.152469
  18. Morales AR, Schafer-Hales KJ, Yanez CO, et al. Excited state intramolecular proton transfer and photophysics of a new fluorenyl two-photon fluorescent probe. Chemphyschem. 2009;10(12):2073-2081. doi: 10.1002/cphc.200900032
  19. Serbin J, Egbert A, Ostendorf A, et al. Femtosecond laser-induced two-photon polymerization of inorganic–organic hybrid materials for applications in photonics. Opt Lett. 2003;28(5):301-303. doi: 10.1364/OL.28.000301
  20. Gan Z, Cao Y, Evans R, et al. Three-dimensional deep sub-diffraction optical beam lithography with 9 nm feature size. Nat Commun. 2013;4:2061. doi: 10.1038/ncomms3061
  21. Florczak S, Größbacher G, Ribezzi D, et al. Adaptive and context-aware volumetric printing. Nature. 2025;645:108-114. doi: 10.1038/s41586-025-09436-7
  22. Kim D, Kang D, Kim D, Jang J. Volumetric bioprinting strategies for creating large-scale tissues and organs. MRS Bull. 2023;48:657-667. doi: 10.1557/s43577-023-00541-4
  23. Negrini NC, Volponi AA, Sharpe PT, et al. Tunable cross-linking and adhesion of gelatin hydrogels via bioorthogonal click chemistry. ACS Biomater Sci Eng. 2021;7(9):4330-4346. doi: 10.1021/acsbiomaterials.1c00136
  24. Yue K, Trujillo-de Santiago G, Alvarez MM, et al. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254-271. doi: 10.1016/j.biomaterials.2015.08.045
  25. Kurian AG, Singh RK, Patel KD, et al. Multifunctional GelMA platforms with nanomaterials for advanced tissue therapeutics. Bioact Mater. 2022;8:267-295. doi: 10.1016/j.bioactmat.2021.06.027
  26. Ford MC, Bertram JP, Hynes SR, et al. A macroporous hydrogel for the coculture of neural progenitor and endothelial cells to form functional vascular networks in vivo. Proc Natl Acad Sci USA. 2006;103:2512-2517. doi: 10.1073/pnas.0506020102
  27. Xing JF, Zheng ML, Duan XM. Two-photon polymerization microfabrication of hydrogels: an advanced 3D printing technology for tissue engineering and drug delivery. Chem Soc Rev. 2015;44:5031-5039. doi: 10.1039/C5CS00278H
  28. Jia Y, Spiegel CA, Welle A, et al. Covalent adaptable microstructures via combining two-photon laser printing and alkoxyamine chemistry: toward living 3D microstructures. Adv Funct Mater. 2023;33:2207826. doi: 10.1002/adfm.202207826
  29. Mur M, Kavčič A, Jagodič U, et al. Two-photon 3D printing of functional microstructures inside living cells. Adv Mater. 2026;38(25):2519286. doi: 10.1002/adma.202519286
  30. Malinauskas M, Žukauskas A, Hasegawa S, et al. Ultrafast laser processing of materials: from science to industry. Light Sci Appl. 2016;5(8):e16133. doi: 10.1038/lsa.2016.133
  31. Ovsianikov A, Deiwick A, Van Vlierberghe S, et al. Laser fabrication of three-dimensional CAD scaffolds from photosensitive gelatin for applications in tissue engineering. Biomacromolecules. 2011;12(4):851-858. doi: 10.1021/bm1015305
  32. Gou M, Qu X, Zhu W, et al. Bio-inspired detoxification using 3D-printed hydrogel nanocomposites. Nat Commun. 2014;5:3774. doi: 10.1038/ncomms4774
  33. Zhu W, Qu X, Zhu J, et al. Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture. Biomaterials. 2017;124:106-115. doi: 10.1016/j.biomaterials.2017.01.042
  34. Tumbleston JR, Shirvanyants D, Ermoshkin N, et al. Continuous liquid interface production of 3D objects. Science. 2015;347(6228):1349-1352. doi: 10.1126/science.aaa2397
  35. Bernal PN, Delrot P, Loterie D, et al. Volumetric bioprinting of complex living-tissue constructs within seconds. Adv Mater. 2019;31(42):1904209. doi: 10.1002/adma.201904209
  36. Zhao S, et al. Spatial light modulator-based printing technologies for optical elements fabrication with different materials. J Manuf Process. 2025;144:60-77. doi: 10.1016/j.jmapro.2025.04.019
  37. Ge Q, et al. Projection micro stereolithography based 3D printing and its applications. Int J Extrem Manuf. 2020;2(2):022004. doi: 10.1088/2631-7990/ab8d9a
  38. Chen J, 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
  39. Beyer M, et al. Comparative evaluation of SLA and DLP 3D printing in dental implant guides: impact on fabrication accuracy, speed, and resin usage. Dent J (Basel). 2025;13(10):471. doi: 10.3390/dj13100471
  40. Liu D, et al. Engineering tridimensional hydrogel tissue and organ phantoms with tunable springiness. Adv Funct Mater. 2023;33(17):2214885. doi: 10.1002/adfm.202214885
  41. Sun Y, et al. Projection stereolithography 3D printing high-conductive hydrogel for flexible passive wireless sensing. Adv Mater. 2024;36(25):2400103. doi: 10.1002/adma.202400103
  42. Maines EM, Porwal MK, Ellison CJ, Reineke TM. Sustainable advances in SLA/DLP 3D printing materials and processes. Green Chem. 2021;23(18):6863-6897. doi: 10.1039/D1GC01489G
  43. Kaijage DJ, Lee BJ. Multiphysics simulation of continuous liquid interface production (CLIP) 3D printing technology. Int J Precis Eng Manuf Green Technol. 2025;12(2):541-552. doi: 10.1007/s40684-024-00673-1
  44. Van Der Laan HL, Burns MA, Scott TF. Volumetric photopolymerization confinement through dual-wavelength photoinitiation and photoinhibition. ACS Macro Lett. 2019;8(8):899-904. doi: 10.1021/acsmacrolett.9b00412
  45. Mathur V, Dsouza V, Srinivasan V, et al. Volumetric additive manufacturing for cell printing: bridging industry adaptation and regulatory frontiers. ACS Biomater Sci Eng. 2025;11(1):156-181. doi: 10.1021/acsbiomaterials.4c01837
  46. Whyte DJ, Doeven EH, Sutti A, Kouzani AZ, Adams SD. Volumetric additive manufacturing: a new frontier in layer-less 3D printing. Addit Manuf. 2024;84:104094. doi: 10.1016/j.addma.2024.104094
  47. Bernal PN, Florczak S, Inacker S, et al. The road ahead in materials and technologies for volumetric 3D printing. Nat Rev Mater. 2025;10:826-841. doi: 10.1038/s41578-025-00785-3
  48. Lü JQ, Sun JS, Jia RP, et al. Erosion-free penalty minimization optimization for high-fidelity computed axial lithography. Addit Manuf. 2025;111:104990. doi: 10.1016/j.addma.2025.104990
  49. Kelly BE, Bhattacharya I, Heidari H, et al. Volumetric additive manufacturing via tomographic reconstruction. Science. 2019;363(6431):1075-1079. doi: 10.1126/science.aau7114
  50. Toombs JT, Luitz M, Cook CC, et al. Volumetric additive manufacturing of silica glass with microscale computed axial lithography. Science. 2022;376(6590):308-312. doi: 10.1126/science.abm6459
  51. Regehly M, Garmshausen Y, Reuter M, et al. Xolography for linear volumetric 3D printing. Nature. 2020;588(7839):620-624. doi: 10.1038/s41586-020-3029-7
  52. Ding S, He S, Shen L, et al. An instructional design strategy for optimization of GelMA hydrogels material properties. Eur Polym J. 2024;218:113336. doi: 10.1016/j.eurpolymj.2024.113336
  53. Gehlen J, Qiu W, Schädli GN, et al. Tomographic volumetric bioprinting of heterocellular bone-like tissues in seconds. Acta Biomater. 2023;156:49-60. doi: 10.1016/j.actbio.2022.06.020
  54. Melde K, Mark AG, Qiu T, et al. Holograms for acoustics. Nature. 2016;537(7621):518-522. doi: 10.1038/nature19755
  55. Zhang M, Jin B, Hua Y, et al. Reconfigurable dynamic acoustic holography with acoustically transparent and programmable metamaterial. Nat Commun. 2025;16(1):9126. doi: 10.1038/s41467-025-64154-y
  56. Derayatifar M, Habibi M, Bhat R, Packirisamy M. Holographic direct sound printing. Nat Commun. 2024;15:6691. doi: 10.1038/s41467-024-50923-8
  57. Li X, Xiu Y, Lee K, Zhang J, Corrigan N, Boyer C. Xolography for rapid volumetric production of objects from the nanoscopic to macroscopic length scales. Adv Mater. 2025;37(37):2503245. doi: 10.1002/adma.202503245
  58. Álvarez-Castaño MI, Madsen AG, Glückstad J, et al. Holographic beam shaping for volumetric 3D printing. In: Advanced Fabrication Technologies for Micro/Nano Optics and Photonics XVII. Bellingham, WA: SPIE; 2024:42. doi: 10.1117/12.3001404
  59. Álvarez-Castaño MI, et al. Holographic tomographic volumetric additive manufacturing. Nat Commun. 2025;16(1):1551. doi: 10.1038/s41467-025-56852-4
  60. Liu C, et al. Correction of a digital micromirror device lithography system for fabrication of a pixelated liquid crystal micropolarizer array. Opt Express. 2022;30(7):12014. doi: 10.1364/OE.453800
  61. Lim Y, Hahn J, Lee B. Phase-conjugate holographic lithography based on micromirror array recording. Appl Opt. 2011;50(34):H68. doi: 10.1364/AO.50.000H68
  62. Thijssen Q, Toombs J, Li CC, Taylor H, Van Vlierberghe S. From pixels to voxels: a mechanistic perspective on volumetric 3D-printing. Prog Polym Sci. 2023;147:101755. doi: 10.1016/j.progpolymsci.2023.101755
  63. Fairbanks BD, Schwartz MP, Bowman CN, Anseth KS. Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. Biomaterials. 2009;30(35):6702-6707. doi: 10.1016/j.biomaterials.2009.08.055
  64. Topa-Skwarczyńska M, et al. Increasing resolution in additive manufacturing by using high-performance and non-toxic photoinitiating systems. Addit Manuf. 2024;94:104473. doi: 10.1016/j.addma.2024.104473
  65. Elkhoury K, Zuazola J, Vijayavenkataraman S. Bioprinting the future using light: a review on photocrosslinking reactions, photoreactive groups, and photoinitiators. SLAS Technol. 2023;28(3):142-151. doi: 10.1016/j.slast.2023.02.003
  66. Lian L, et al. Rapid volumetric bioprinting of decellularized extracellular matrix bioinks. Adv Mater. 2024;36(34):2304846. doi: 10.1002/adma.202304846
  67. Wolfel A, et al. Bioxolography using diphenyliodonium chloride and N-vinylpyrrolidone enables rapid high-resolution volumetric 3D printing of spatially encoded living matter. Adv Mater. 2025;37(37):2501052. doi: 10.1002/adma.202501052
  68. Dogan E, Austin A, Pourmostafa A, Yogeshwaran S, Hosseinabadi HG, Miri AK. Design considerations for photoinitiator selection in cell-laden gelatin methacryloyl hydrogels. Biomater Sci. 2026;14(3):807-816. doi: 10.1039/D5BM00550G
  69. Madrid-Wolff J, Boniface A, Loterie D, Delrot P, Moser C. Controlling light in scattering materials for volumetric additive manufacturing. Adv Sci (Weinh). 2022;9(22):2105144. doi: 10.1002/advs.202105144
  70. You S, et al. High cell density and high-resolution 3D bioprinting for fabricating vascularized tissues. Sci Adv. 2023;9(8):eade7923. doi: 10.1126/sciadv.ade7923
  71. Bernal PN, Bouwmeester M, Madrid-Wolff J, et al. Volumetric bioprinting of organoids and optically tuned hydrogels to build liver-like metabolic biofactories. Adv Mater. 2022;34(15):2110054. doi: 10.1002/adma.202110054
  72. He N, et al. Photoinhibiting via simultaneous photoabsorption and free-radical reaction for high-fidelity light-based bioprinting. Nat Commun. 2023;14(1):3063. doi: 10.1038/s41467-023-38838-2
  73. Madrid-Wolff J, et al. A review of materials used in tomographic volumetric additive manufacturing. MRS Commun. 2023;13(5):764-785. doi: 10.1557/s43579-023-00447-x
  74. Jain T, et al. Impact of cell density on the bioprinting of gelatin methacrylate (GelMA) bioinks. Bioprinting. 2021;22:e00131. doi: 10.1016/j.bprint.2021.e00131
  75. Dubbin K, Tabet A, Heilshorn SC. Quantitative criteria to benchmark new and existing bio-inks for cell compatibility. Biofabrication. 2017;9(4):044102. doi: 10.1088/1758-5090/aa869f
  76. Ribezzi D, et al. Shaping synthetic multicellular and complex multimaterial tissues via embedded extrusion-volumetric printing of microgels. Adv Mater. 2023;35(36):2301673. doi: 10.1002/adma.202301673
  77. Liu J, Shahriar M, Xu H, Xu C. Cell-laden bioink circulation-assisted inkjet-based bioprinting to mitigate cell sedimentation and aggregation. Biofabrication. 2022;14(4):045020. doi: 10.1088/1758-5090/ac8fb7
  78. An C, et al. The microparticulate inks for bioprinting applications. Mater Today Bio. 2024;24:100930. doi: 10.1016/j.mtbio.2023.100930
  79. Duquesne J, et al. Volumetric bioprinting of the osteoid niche. Biofabrication. 2025;17(2):025002. doi: 10.1088/1758-5090/adab25
  80. Qiu W, Gehlen J, Bernero M, et al. A synthetic dynamic polyvinyl alcohol photoresin for fast volumetric bioprinting of functional ultrasoft hydrogel constructs. Adv Funct Mater. 2023;33(20):2214393. doi: 10.1002/adfm.202214393
  81. Longoni A, Bernal PN, Falandt M, Ribezzi D, Levato R. Volumetric biofabrication strategies for regenerative medicine applications and tissue vascularization. Bone Joint J. 2025;107-B(suppl 6):40. doi: 10.1302/1358-992X.2025.6.040
  82. Ribezzi D, et al. Multi-material volumetric bioprinting and plug-and-play suspension bath biofabrication via bioresin molecular weight tuning and via multiwavelength alignment optics. Adv Mater. 2025;37(13):2409355. doi: 10.1002/adma.202409355
  83. Akbari M, Khademhosseini A. Tissue bioprinting for biology and medicine. Cell. 2022;185(15):2644-2648. doi: 10.1016/j.cell.2022.06.015
  84. Chansoria P, et al. Synergizing algorithmic design, photoclick chemistry and multi-material volumetric printing for accelerating complex shape engineering. Adv Sci (Weinh). 2023;10(26):2300912. doi: 10.1002/advs.202300912
  85. Kim W, Kim G. Engineered 3D liver-tissue model with minispheroids formed by a bioprinting process supported with in situ electrical stimulation. Bioact Mater. 2024;35:382-400. doi: 10.1016/j.bioactmat.2024.02.001
  86. Zhang X, Zhang X, Li Y, Zhang Y. Applications of light-based 3D bioprinting and photoactive biomaterials for tissue engineering. Materials (Basel). 2023;16(23):7461. doi: 10.3390/ma16237461
  87. Yang M, et al. Multi-material digital light processing (DLP) bioprinting of heterogeneous hydrogel constructs with perfusable networks. Adv Funct Mater. 2024;34(32):2316456. doi: 10.1002/adfm.202316456
  88. Subramanian A, et al. Reviewing the literature of 3D printing of bones and cartilage: evidence and practice. Ann 3D Print Med. 2024;16:100180. doi: 10.1016/j.stlm.2024.100180
  89. Zhou J, Li Q, Tian Z, Yao Q, Zhang M. Recent advances in 3D bioprinted cartilage-mimicking constructs for applications in tissue engineering. Mater Today Bio. 2023;23:100870. doi: 10.1016/j.mtbio.2023.100870
  90. Hao S, Wang M, Yin Z, Jing Y, Bai L, Su J. Microenvironment-targeted strategy steers advanced bone regeneration. Mater Today Bio. 2023;22:100741. doi: 10.1016/j.mtbio.2023.100741
  91. Xiang Y, et al. Iohexol as a refractive index tuning agent for bioinks in high cell density bioprinting. Biomater Sci. 2025;13(14):3958-3971. doi: 10.1039/D5BM00585J
  92. Guan J, et al. Compensating the cell-induced light scattering effect in light-based bioprinting using deep learning. Biofabrication. 2022;14(1):015011. doi: 10.1088/1758-5090/ac3b92
  93. Li F, et al. Efficient light-based bioprinting via rutin nanoparticle photoinhibitor for advanced biomedical applications. ACS Nano. 2024;18(33):22104-22121. doi: 10.1021/acsnano.4c05380
  94. Lee SJ, Jeong W, Atala A. 3D bioprinting for engineered tissue constructs and patient-specific models: current progress and prospects in clinical applications. Adv Mater. 2024;36(49):2408032. doi: 10.1002/adma.202408032
  95. Yang S, Wang L, Chen Q, Xu M. In situ process monitoring and automated multi-parameter evaluation using optical coherence tomography during extrusion-based bioprinting. Addit Manuf. 2021;47:102251. doi: 10.1016/j.addma.2021.102251
  96. Tashman JW, et al. In situ volumetric imaging and analysis of FRESH 3D bioprinted constructs using optical coherence tomography. Biofabrication. 2023;15(1):014102. doi: 10.1088/1758-5090/ac975e
  97. Sexton ZA, et al. Rapid model-guided design of organ-scale synthetic vasculature for biomanufacturing. Science. 2025;388(6752):1198-1204. doi: 10.1126/science.adj6152
  98. Levato R, Lim KS. Harnessing light in biofabrication. Biofabrication. 2023;15(2):020401. doi: 10.1088/1758-5090/acb50f
  99. Guo Y, Wu Y, Li Y, Rao X, Rao C. Deep phase retrieval for astronomical Shack–Hartmann wavefront sensors. Mon Not R Astron Soc. 2022;510(3):4347-4354. doi: 10.1093/mnras/stab3690
  100. Florczak S, et al. Multi-material integration in light-based volumetric bioprinting: pathways to enhanced precision and complexity in scaffold fabrication. In: von Freymann G, Blasco E, Chanda D, eds. Advanced Fabrication Technologies for Micro/Nano Optics and Photonics XVII. Bellingham, WA: SPIE; 2024:38. doi: 10.1117/12.3008912
  101. Keding C. Understanding the interplay of artificial intelligence and strategic management: four decades of research in review. Manag Rev Q. 2021;71(1):91-134. doi: 10.1007/s11301-020-00181-x
  102. Meyer TA, Ramirez C, Tamasi MJ, Gormley AJ. A user's guide to machine learning for polymeric biomaterials. ACS Polym Au. 2023;3(2):141-157. doi: 10.1021/acspolymersau.2c00037
  103. Ng WL, Chan A, Ong YS, Chua CK. Deep learning for fabrication and maturation of 3D bioprinted tissues and organs. Virtual Phys Prototyp. 2020;15(3):340-358. doi: 10.1080/17452759.2020.1771741
  104. Maharjan S, et al. Advanced 3D imaging and organoid bioprinting for biomedical research and therapeutic applications. Adv Drug Deliv Rev. 2024;208:115237. doi: 10.1016/j.addr.2024.115237
  105. Bhardwaj N, Dey S, Bhar B, Mandal BB. Bioprinted in vitro tissue models: an emerging platform for developing therapeutic interventions and disease modelling. Prog Biomed Eng. 2024;6(1):012003. doi: 10.1088/2516-1091/ad10b4
  106. Xu K, Han Y, Huang Y, et al. The application of 3D bioprinting in urological diseases. Mater Today Bio. 2022;16:100388. doi: 10.1016/j.mtbio.2022.100388
  107. Liu H, Wu C, Lin S, et al. Advances in 3D and 4D printing of soft robotics and their applications. Adv Intell Syst. 2025;7:2400699. doi: 10.1002/aisy.202400699
  108. De Reguardati S, Pahapill J, Mikhailov A, et al. High-accuracy reference standards for two-photon absorption in the 680–1050 nm wavelength range. Opt Express. 2016;24:9053. doi: 10.1364/OE.24.009053
  109. You S, Li J, Zhu W, et al. Nanoscale 3D printing of hydrogels for cellular tissue engineering. J Mater Chem B. 2018;6:2187-2197. doi: 10.1039/C8TB00301G
  110. He M, Zhang Z, Cao C, et al. 3D sub-diffraction printing by multicolor photoinhibition lithography: from optics to chemistry. Laser Photonics Rev. 2022;16:2100229. doi: 10.1002/lpor.202100229
  111. Taale M, Schamberger B, Taheri F, et al. In situ fabrication of constraints for multicellular micro-spheroids using two-photon lithography. Adv Funct Mater. 2024;34:2302356. doi: 10.1002/adfm.202302356
  112. Bouwmeester MC, Bernal PN, Oosterhoff LA, et al. Bioprinting of human liver-derived epithelial organoids for toxicity studies. Macromol Biosci. 2021;21:2100327. doi: 10.1002/mabi.202100327
  113. Gebinoga M, Katzmann J, Fernekorn U, et al. Multi-photon structuring of native polymers: a case study for structuring natural proteins. Eng Life Sci. 2013;13:368-375. doi: 10.1002/elsc.201200152
  114. Zhou X, Liu X, Gu Z. Photoresist development for 3D printing of conductive microstructures via two-photon polymerization. Adv Mater. 2024;36:2409326. doi: 10.1002/adma.202409326
  115. Paradowska-Stolarz A, Wezgowiec J, Malysa A, et al. Effects of polishing and artificial aging on mechanical properties of dental LT clear resin. J Funct Biomater. 2023;14:295. doi: 10.3390/jfb14060295
  116. Haas KH, Wolter H. Synthesis, properties and applications of inorganic–organic copolymers (ORMOCER). Curr Opin Solid State Mater Sci. 1999;4(6):571-580. doi: 10.1016/S1359-0286(00)00009-7
  117. Schlie S, Ngezahayo A, Ovsianikov A, et al. Three-dimensional cell growth on structures fabricated from ORMOCER® by two-photon polymerization technique. J Biomater Appl. 2007;22:275-287. doi: 10.1177/0885328207077590
  118. Schwegler N, Gebert T, Villiou M, et al. Multimaterial 3D laser printing of cell-adhesive and cell-repellent hydrogels. Small. 2024;20:2401344. doi: 10.1002/smll.202401344
  119. Zhu W, Huo FY, Cao LM, et al. Two-photon polymerization 3D printing of biomimetic microstructures for functionalizing surfaces to inhibit bacterial growth. Chem Eng J. 2025;511:161907. doi: 10.1016/j.cej.2025.161907
  120. Tezel Ö, Kahraman MV, Ceylan R, et al. Usage of 3D-printed scaffolds manufactured with bio-based photopolymer resin via 3D DLP in tissue engineering. J Polym Environ. 2025;33:3013-3028. doi: 10.1007/s10924-025-03592-7
  121. He Z, Chen F, He S. Fabrication of microneedles using two photon-polymerization with low numerical aperture. Opt Commun. 2024;553:130093. doi: 10.1016/j.optcom.2023.130093
  122. Yao Z, Zhang X, Yu W, et al. Scaffolds fabricated via two-photon polymerisation for regulating cell morphology and differentiation. Virtual Phys Prototyp. 2025;20(1):2447934. doi: 10.1080/17452759.2024.2447934
  123. Bran A, Orobeti S, Jipa F, et al. Tissue-like scaffolds created by two-photon polymerization for testing cancer cell behavior in confined environments. ACS Appl Bio Mater. 2025;8(8):7344-7356. doi: 10.1021/acsabm.5c01009
  124. Rengaraj A, Bosc L, Machillot P, et al. Engineering of a microscale niche for pancreatic tumor cells using bioactive film coatings combined with 3D-architectured scaffolds. ACS Appl Mater Interfaces. 2022;14:13107-13121. doi: 10.1021/acsami.2c01747
  125. Accardo A, Blatché MC, Courson R, et al. Multi-photon direct laser writing and 3D imaging of polymeric freestanding architectures for cell colonization. Small. 2017;13(27):1700621. doi: 10.1002/smll.201700621
  126. Costa BNL, Adão RMR, Maibohm C, et al. Cellular interaction of bone marrow mesenchymal stem cells with polymer and hydrogel 3D microscaffold templates. ACS Appl Mater Interfaces. 2022;14:13013-13024. doi: 10.1021/acsami.1c23442
  127. Gartner ZJ, Hu JL. Guiding tissue-scale self-organization. Nat Mater. 2021;20:2-3. doi: 10.1038/s41563-020-00885-1
  128. Breslin S, O'Driscoll L. Three-dimensional cell culture: the missing link in drug discovery. Drug Discov Today. 2013;18:240-249. doi: 10.1016/j.drudis.2012.10.003
  129. Edmondson R, Adcock AF, Yang L. Influence of matrices on 3D-cultured prostate cancer cells' drug response and expression of drug-action associated proteins. PLoS One. 2016;11(6):e0158116. doi: 10.1371/journal.pone.0158116
  130. He Z, He S. Two-photon polymerization of hydrogel cellular scaffolds. Opt Commun. 2025;574:131161. doi: 10.1016/j.optcom.2024.131161
  131. Fu H, Yu B. 3D micro/nano hydrogel structures fabricated by two-photon polymerization for biomedical applications. Front Bioeng Biotechnol. 2024;12:1339450. doi: 10.3389/fbioe.2024.1339450
  132. Torgersen J, Qin XH, Li Z, et al. Hydrogels for two-photon polymerization: a toolbox for mimicking the extracellular matrix. Adv Funct Mater. 2013;23:4542-4554. doi: 10.1002/adfm.201203880
  133. Santos LMS, Oliveira JM, Oliveira LFAM, et al. Two-photon polymerizable nanocomposites incorporating Brazilian red propolis for tailored wound healing applications. J Polym Sci. 2025;63:3978-3989. doi: 10.1002/pol.20250266
  134. Yarali E, Mubeen AA, Cussen K, et al. Two-photon polymerization based 4D printing of poly(N-isopropylacrylamide) hydrogel microarchitectures for reversible shape morphing. Sci Rep. 2025;15:21549. doi: 10.1038/s41598-025-06269-2
  135. Song J, Michas C, Chen CS, et al. Controlled cell alignment using two-photon direct laser writing-patterned hydrogels in 2D and 3D. Macromol Biosci. 2021;21:2100051. doi: 10.1002/mabi.202100051
  136. Jeon H, Hidai H, Hwang DJ, et al. Fabrication of arbitrary polymer patterns for cell study by two-photon polymerization process. J Biomed Mater Res A. 2010;93A:56-66. doi: 10.1002/jbm.a.32517
  137. Richter B, Hahn V, Bertels S, et al. Guiding cell attachment in 3D microscaffolds selectively functionalized with two distinct adhesion proteins. Adv Mater. 2017;29:1604342. doi: 10.1002/adma.201604342
  138. Colombo F, Taale M, Taheri F, et al. Two-photon laser printing to mechanically stimulate multicellular systems in 3D. Adv Funct Mater. 2024;34:2303601. doi: 10.1002/adfm.202303601
  139. Turunen S, Joki T, Hiltunen ML, et al. Direct laser writing of tubular microtowers for 3D culture of human pluripotent stem cell-derived neuronal cells. ACS Appl Mater Interfaces. 2017;9:25717-25730. doi: 10.1021/acsami.7b05536
  140. Eren TN, Liang J, Schneider JLG, et al. Soft and stiff 3D microstructures by step-growth photopolymerization using a single photoresin and multi-photon laser printing. Adv Funct Mater. 2026;36(5):2502876. doi: 10.1002/adfm.202502876
  141. Hohmann JK, Von Freymann G. Influence of direct laser written 3D topographies on proliferation and differentiation of osteoblast-like cells: towards improved implant surfaces. Adv Funct Mater. 2014;24:6573-6580. doi: 10.1002/adfm.201401390
  142. Koroleva A, Deiwick A, El-Tamer A, et al. In vitro development of human iPSC-derived functional neuronal networks on laser-fabricated 3D scaffolds. ACS Appl Mater Interfaces. 2021;13:7839-7853. doi: 10.1021/acsami.0c16616
  143. Marino A, Tricinci O, Battaglini M, et al. A 3D real-scale, biomimetic, and biohybrid model of the blood-brain barrier fabricated through two-photon lithography. Small. 2018;14:1702959. doi: 10.1002/smll.201702959
  144. Gullo MR, Takeuchi S, Paul O. Multicellular biohybrid materials: probing the interplay of cells of different types precisely positioned and constrained on 3D wireframe-like microstructures. Adv Healthc Mater. 2017;6:1601053. doi: 10.1002/adhm.201601053
  145. Ma ZC, Zhang YL, Han B, et al. Femtosecond laser programmed artificial musculoskeletal systems. Nat Commun. 2020;11:4536. doi: 10.1038/s41467-020-18117-0
  146. Binder S, Chalupa-Gantner F, Yoo HW, et al. Two-photon polymerization system based on a resonant scanner for high-throughput production of tissue engineering microscaffolds. Addit Manuf. 2025;97:104601. doi: 10.1016/j.addma.2024.104601
  147. Van Der Sanden B, Gredy L, Wion D, et al. 3D two-photon polymerization of smart cell gelatin–collagen matrixes with incorporated ruthenium complexes for the monitoring of local oxygen tensions. Acta Biomater. 2021;130:172-182. doi: 10.1016/j.actbio.2021.06.021
  148. Zandrini T, Shan O, Parodi V, et al. Multi-foci laser microfabrication of 3D polymeric scaffolds for stem cell expansion in regenerative medicine. Sci Rep. 2019;9:11761. doi: 10.1038/s41598-019-48080-w
  149. Weisgrab G, Guillaume O, Guo Z, et al. 3D printing of large-scale and highly porous biodegradable tissue engineering scaffolds from poly(trimethylene-carbonate) using two-photon-polymerization. Biofabrication. 2020;12:045036. doi: 10.1088/1758-5090/abb539
  150. Torgersen J, Ovsianikov A, Mironov V, et al. Photo-sensitive hydrogels for three-dimensional laser microfabrication in the presence of whole organisms. J Biomed Opt. 2012;17:105008. doi: 10.1117/1.JBO.17.10.105008
  151. Wagner S, Siegle L, Haeusler S, et al. From two-photon grayscale lithography to scalable replication: enabling complex aspherical micro-optics for mass production. Adv Opt Mater. 2025;13(30):2502089. doi: 10.1002/adom.202502089
  152. Lemma ED, Spagnolo B, De Vittorio M, et al. Studying cell mechanobiology in 3D: the two-photon lithography approach. Trends Biotechnol. 2019;37:358-372. doi: 10.1016/j.tibtech.2018.09.008
  153. Brassard JA, Lutolf MP. Engineering stem cell self-organization to build better organoids. Cell Stem Cell. 2019;24(6):860-876. doi: 10.1016/j.stem.2019.05.005
  154. Gjorevski N, Nikolaev M, Brown TE, et al. Tissue geometry drives deterministic organoid patterning. Science. 2022;375(6576):eaaw9021. doi: 10.1126/science.aaw9021
  155. Lawlor KT, Vanslambrouck JM, Higgins JW, et al. Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nat Mater. 2021;20:260-271. doi: 10.1038/s41563-020-00853-9
  156. Zhang Z, Wu Y, Xuan Z, et al. Self-assembly of three-dimensional liver organoids: virtual reconstruction via endocytosed polymer dots for refactoring the fine structure. Biomater Sci. 2023;11:7867-7883. doi: 10.1039/D3BM01174G
  157. Dobos A, Van Hoorick J, Steiger W, et al. Thiol–gelatin–norbornene bioink for laser-based high-definition bioprinting. Adv Healthc Mater. 2020;9:1900752. doi: 10.1002/adhm.201900752
  158. Stichel T. Two-photon polymerization as method for the fabrication of large scale biomedical scaffold applications. J Laser Micro Nanoeng. 2010;5:209-212. doi: 10.2961/jlmn.2010.03.0005
  159. Hidai H, Jeon H, Hwang DJ, et al. Self-standing aligned fiber scaffold fabrication by two photon photopolymerization. Biomed Microdevices. 2009;11:643-652. doi: 10.1007/s10544-008-9274-4
  160. Huang X, Zhang Y, Shi M, et al. A highly biocompatible bio-ink for 3D hydrogel scaffolds fabrication in the presence of living cells by two-photon polymerization. Eur Polym J. 2021;153:110505. doi: 10.1016/j.eurpolymj.2021.110505
  161. Vitkūnaitė E, Žymantaitė E, Mlynska A, et al. Advancing 3D spheroid research through 3D scaffolds made by two-photon polymerization. Bioengineering (Basel). 2024;11:902. doi: 10.3390/bioengineering11090902
  162. Shin J, Tabatabaei Rezaei N, Choi S, et al. Photocrosslinkable kidney decellularized extracellular matrix-based bioink for 3D bioprinting. Adv Healthc Mater. 2025;14:2501616. doi: 10.1002/adhm.202501616
  163. Brassard JA, Nikolaev M, Hübscher T, Hofer M, Lutolf MP. Recapitulating macro-scale tissue self-organization through organoid bioprinting. Nat Mater. 2021;20:22-29. doi: 10.1038/s41563-020-00803-5
  164. Skylar-Scott MA, Uzel SGM, Nam LL, et al. Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels. Sci Adv. 2019;5(9):eaaw2459. doi: 10.1126/sciadv.aaw2459
  165. Navarro JF, Crilly S, Chan WK, et al. Cerebral organoids with integrated endothelial networks emulate the neurovascular unit and mitigate core necrosis. Adv Sci (Weinh). 2025;12(43):2507256. doi: 10.1002/advs.202507256
  166. Antich C, Kundu S, Frebert S, Voss T, Song MJ, Ferrer M. Bioprinting spatially guided functional 3D neural circuits with agarose-xanthan gum copolymer hydrogels. Biomaterials. 2025;318:123156. doi: 10.1016/j.biomaterials.2025.123156
  167. Homan KA, Gupta N, Kroll KT, et al. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat Methods. 2019;16(3):255-262. doi: 10.1038/s41592-019-0325-y
  168. Kang SY, Kimura M, Shrestha S, et al. A pillar and perfusion plate platform for robust human organoid culture and analysis. Adv Healthc Mater. 2024;13(21):2302502. doi: 10.1002/adhm.202302502
  169. Al Reza H, Santangelo C, Iwasawa K, et al. Multi-zonal liver organoids from human pluripotent stem cells. Nature. 2025;641(8065):1258-1267. doi: 10.1038/s41586-025-08850-1
  170. Schuster B, Junkin M, Kashaf SS, et al. Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids. Nat Commun. 2020;11(1):5271. doi: 10.1038/s41467-020-19058-4
  171. Caporale N, Leemans M, Birgersson L, et al. From cohorts to molecules: adverse impacts of endocrine disrupting mixtures. Science. 2022;375(6582):eabe8244. doi: 10.1126/science.abe8244
  172. Romaldini A, Spanò R, Veronesi M, Grimaldi B, Bandiera T, Sabella S. Human multi-lineage liver organoid model reveals impairment of CYP3A4 expression upon repeated exposure to graphene oxide. Cells. 2024;13(18):1542. doi: 10.3390/cells13181542
  173. Urciuolo A, Giobbe GG, Dong Y, et al. Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures. Nat Commun. 2023;14(1):3128. doi: 10.1038/s41467-023-37953-4
  174. Crowe JA, El-Tamer A, Nagel D, et al. Development of two-photon polymerised scaffolds for optical interrogation and neurite guidance of human iPSC-derived cortical neuronal networks. Lab Chip. 2020;20(10):1792-1806. doi: 10.1039/C9LC01209E
  175. Harris N, Zou M. Controlling the organization and differentiation of human neural stem cells on Hilbert microcapillary scaffolds fabricated via two-photon lithography. Adv Healthc Mater. 2026;15(2):2501355. doi: 10.1002/adhm.202501355
  176. Lancaster MA, Knoblich JA. Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc. 2014;9(10):2329-2340. doi: 10.1038/nprot.2014.158
  177. Han H, Lee S, Gao G, Yi HG, Paek SH, Jang J. Cerebrovascular-specific extracellular matrix bioink promotes blood–brain barrier properties. Biomater Res. 2024;28:0115. doi: 10.34133/bmr.0115
  178. Wang X, Ma Y, Niu Y, et al. Sub-second volumetric 3D printing by synthesis of holographic light fields. Nature. 2026;650:882-890. doi: 10.1038/s41586-026-10114-5
  179. Wang HY, Gao FY, Shi Y, et al. Sparse-view irradiation processing volumetric additive manufacturing. Int J Extrem Manuf. 2025;7(6):065001. doi: 10.1088/2631-7990/adebbf
  180. Han G, Lavoie NS, Patil N, et al. 3D-printed scaffolds promote enhanced spinal organoid formation for use in spinal cord injury. Adv Healthc Mater. 2025;14(24):2404817. doi: 10.1002/adhm.202404817
  181. Hariharan A, Ackermann M, Koss S, et al. High-speed 3D printing coupled with machine learning to accelerate alloy development for additive manufacturing. Adv Sci (Weinh). 2025;12(17):2414880. doi: 10.1002/advs.202414880
  182. Tan C, Li Q, Yao X, et al. Machine learning customized novel material for energy-efficient 4D printing. Adv Sci (Weinh). 2023;10(10):2206607. doi: 10.1002/advs.202206607
Next article in this issue
Share
Back to top
International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept