Lithography-based 3D printing of hydrogels | Nature Reviews Bioengineering
Nature Reviews Bioengineering (2024)Cite this article
2 Altmetric
Metrics details
Additive manufacturing is an engineering tool that enables the creation of complex structures for biomedical use, such as 3D scaffolds for tissue engineering and regenerative medicine, as well as in vitro disease models for drug testing. In particular, lithography-based techniques such as digital light processing and volumetric additive manufacturing have enabled advances in the 3D processing of photoreactive resins into structured hydrogels. In this Review, we introduce light-based lithographic 3D printing methods to process hydrogels and provide a guide to lithography-based printing, from bioresin selection to the optimization of print parameters. Moreover, we highlight examples of in vitro and in vivo biomedical applications of hydrogels, for which lithography-based approaches have been leveraged, and discuss efforts to process hydrogels into heterogeneous structures with multi-scale organization. Finally, we provide a perspective on the challenges and opportunities in this field.
Lithography-based 3D printing achieves high-resolution structures without compromising the speed of fabrication.
Hydrogels can be processed using several lithography-based methods to control hydrogel structure, as well as biochemical and biophysical properties.
Lithography-based printing involves a sequence of steps from resin formulation through post-processing.
Printed hydrogels are promising for applications from tissue engineering to in vitro models for drug screening.
Advanced lithography-based methods are increasing the complexity of printed structures, expanding their use to new applications.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
Prices may be subject to local taxes which are calculated during checkout
Zhang, Y. S. & Khademhosseini, A. Advances in engineering hydrogels. Science 356, eaaf3627 (2017).
Article Google Scholar
Caliari, S. R. & Burdick, J. A. A practical guide to hydrogels for cell culture. Nat. Methods 13, 405–414 (2016).
Article Google Scholar
Blache, U. et al. Engineered hydrogels for mechanobiology. Nat. Rev. Meth. Prim. 2, 98 (2022).
Article Google Scholar
Li, J. & Mooney, D. J. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 1, 16071 (2016).
Article Google Scholar
Yuk, H., Wu, J. & Zhao, X. Hydrogel interfaces for merging humans and machines. Nat. Rev. Mater. 7, 935–952 (2022).
Article Google Scholar
Lim, K. S. et al. Fundamentals and applications of photo-cross-linking in bioprinting. Chem. Rev. 120, 10662–10694 (2020).
Article Google Scholar
Levato, R. et al. Light-based vat-polymerization bioprinting. Nat. Rev. Meth. Prim. 3, 47 (2023).
Article Google Scholar
Madrid-Wolff, J. et al. A review of materials used in tomographic volumetric additive manufacturing. MRS Commun. 13, 764–785 (2023).
Article Google Scholar
Saha, S. K. et al. Scalable submicrometer additive manufacturing. Science 366, 105–109 (2019).
Article Google Scholar
Skylar-Scott, M. A., Liu, M. C., Wu, Y., Dixit, A. & Yanik, M. F. Guided homing of cells in multi-photon microfabricated bioscaffolds. Adv. Healthc. Mater. 5, 1233–1243 (2016).
Article Google Scholar
Rayner, S. G. et al. Multiphoton-guided creation of complex organ-specific microvasculature. Adv. Healthc. Mater. 10, 2100031 (2021).
Article Google Scholar
Tytgat, L. et al. High-resolution 3D bioprinting of photo-cross-linkable recombinant collagen to serve tissue engineering applications. Biomacromolecules 21, 3997–4007 (2020).
Article Google Scholar
Dobos, A. et al. Thiol–gelatin–norbornene bioink for laser-based high-definition bioprinting. Adv. Healthc. Mater. 9, e1900752 (2020).
Article Google Scholar
Loebel, C., Broguiere, N., Alini, M., Zenobi-Wong, M. & Eglin, D. Microfabrication of photo-cross-linked hyaluronan hydrogels by single- and two-photon tyramine oxidation. Biomacromolecules 16, 2624–2630 (2015).
Article Google Scholar
Greant, C., Van Durme, B., Van Hoorick, J. & Van Vlierberghe, S. Multiphoton lithography as a promising tool for biomedical applications. Adv. Funct. Mater. 33, 2212641 (2023).
Article Google Scholar
Koch, T. et al. Approaching standardization: mechanical material testing of macroscopic two-photon polymerized specimens. Adv. Mater. 36, e2308497 (2024).
Article Google Scholar
Grigoryan, B. et al. Multivascular networks and functional intravascular topologies within biocompatible hydrogels. Science 364, 458–464 (2019).
Article Google Scholar
Tumbleston, J. R. et al. Continuous liquid interface production of 3D objects. Science 347, 1349–1352 (2015).
Article Google Scholar
Hsiao, K. et al. Single-digit-micrometer-resolution continuous liquid interface production. Sci. Adv. 8, 2846 (2022).
Article Google Scholar
Lipkowitz, G. et al. Injection continuous liquid interface production of 3D objects. Sci. Adv. 8, 3917 (2022).
Article Google Scholar
Walker, D. A., Hedrick, J. L. & Mirkin, C. A. Rapid, large-volume, thermally controlled 3D printing using a mobile liquid interface. Science 366, 360–364 (2019).
Article Google Scholar
Wu, J. et al. Rapid digital light 3D printing enabled by a soft and deformable hydrogel separation interface. Nat. Commun. 12, 6070 (2021).
Article Google Scholar
Anandakrishnan, N. et al. Fast stereolithography printing of large-scale biocompatible hydrogel models. Adv. Healthc. Mater. 10, 2002103 (2021).
Article Google Scholar
De Beer, M. P. et al. Rapid, continuous additive manufacturing by volumetric polymerization inhibition patterning. Sci. Adv. 5, e2308497 (2019).
Google Scholar
Van Der Laan, H. L., Burns, M. A. & Scott, T. F. Volumetric photopolymerization confinement through dual-wavelength photoinitiation and photoinhibition. ACS Macro Lett. 8, 899–904 (2019).
Article Google Scholar
Beh, C. W. et al. A fluid-supported 3D hydrogel bioprinting method. Biomaterials 276, 121034 (2021).
Article Google Scholar
Murphy, C. A. et al. Next evolution in organ-scale biofabrication: bioresin design for rapid high-resolution vat polymerization. Adv. Mater. 34, 2107759 (2022).
Article Google Scholar
Kelly, B. E. et al. Volumetric additive manufacturing via tomographic reconstruction. Science 363, 1075–1079 (2019).
Article Google Scholar
Shusteff, M. et al. One-step volumetric additive manufacturing of complex polymer structures. Sci. Adv. 3, eaao5496 (2017).
Article Google Scholar
Orth, A. et al. Deconvolution volumetric additive manufacturing. Nat. Commun. 14, 4412 (2023).
Article Google Scholar
Lee, M., Rizzo, R., Surman, F. & Zenobi-Wong, M. Guiding lights: tissue bioprinting using photoactivated materials. Chem. Rev. 120, 10950–11027 (2020).
Article Google Scholar
Qiu, W. et al. A synthetic dynamic polyvinyl alcohol photoresin for fast volumetric bioprinting of functional ultrasoft hydrogel constructs. Adv. Funct. Mater. 33, 2214393 (2023).
Article Google Scholar
Riffe, M. B. et al. Multi-material volumetric additive manufacturing of hydrogels using gelatin as a sacrificial network and 3D suspension bath. Adv. Mater. 36, e2309026 (2024).
Article Google Scholar
Rizzo, R. et al. Optimized photoclick (bio)resins for fast volumetric bioprinting. Adv. Mater. 33, 2102900 (2021).
Article Google Scholar
Thijssen, Q., Toombs, J., Li, C. C., Taylor, H. & Van Vlierberghe, S. From pixels to voxels: a mechanistic perspective on volumetric 3D-printing. Prog. Polym. Sci. 147, 101755 (2023).
Article Google Scholar
Boniface, A., Maitre, F. Madrid-Wolff, J. & Moser, C. Volumetric helical additive manufacturing. Preprint at https://doi.org/10.48550/arXiv.2210.14717 (2022).
Stüwe, L. et al. Continuous volumetric 3D printing: xolography in flow. Adv. Mater. 36, 2306716 (2024).
Article Google Scholar
Loterie, D., Delrot, P. & Moser, C. High-resolution tomographic volumetric additive manufacturing. Nat. Commun. 11, 852 (2020).
Article Google Scholar
Lou, J. & Mooney, D. J. Chemical strategies to engineer hydrogels for cell culture. Nat. Rev. Chem. 6, 726–744 (2022).
Article Google Scholar
Bagheri, A. & Jin, J. Photopolymerization in 3D printing. ACS Appl. Polym. Mater. 1, 593–611 (2019).
Article Google Scholar
Fairbanks, B. D. et al. Photoclick chemistry: a bright idea. Chem. Rev. 121, 6915–6990 (2021).
Article Google Scholar
Northrop, B. H. & Coffey, R. N. Thiol-ene click chemistry: computational and kinetic analysis of the influence of alkene functionality. J. Am. Chem. Soc. 134, 13804–13817 (2012).
Article Google Scholar
Yu, C. et al. Photopolymerizable biomaterials and light-based 3D printing strategies for biomedical applications. Chem. Rev. 120, 10695–10743 (2020).
Article Google Scholar
Zhang, Z., Corrigan, N., Bagheri, A., Jin, J. & Boyer, C. A versatile 3D and 4D printing system through photocontrolled RAFT polymerization. Angew. Chem. Int. Edn Engl. 58, 17954–17963 (2019).
Article Google Scholar
Chen, M., Zhong, M. & Johnson, J. A. Light-controlled radical polymerization: mechanisms, methods, and applications. Chem. Rev. 116, 10167–10211 (2016).
Article Google Scholar
Commisso, A. J., Sama, G. R. & Scott, T. F. Radical-mediated ring-opening photopolymerization for semicrystalline thermoplastic additive manufacturing. Chem. Mater. 35, 3825–3834 (2023).
Article Google Scholar
Dhand, A. P. et al. Simultaneous one-pot interpenetrating network formation to expand 3D processing capabilities. Adv. Mater. 34, e2202261 (2022).
Article Google Scholar
Dhand, A. P. et al. Additive manufacturing of highly entangled polymer networks. Science 385, 566–572 (2024).
Article Google Scholar
Zhu, G. et al. Introducing dynamic bonds in light-based 3D printing. Adv. Funct. Mater. 34, 2300456 (2023).
Article Google Scholar
Caprioli, M. et al. 3D-printed self-healing hydrogels via digital light processing. Nat. Commun. 12, 2462 (2021).
Article Google Scholar
Choi, C. et al. Digital light processing of dynamic bottlebrush materials. Adv. Funct. Mater. 32, 2200883 (2022).
Article Google Scholar
Matsuda, T., Kawakami, R., Namba, R., Nakajima, T. & Gong, J. P. Mechanoresponsive self-growing hydrogels inspired by muscle training. Science 363, 504–508 (2019).
Article Google Scholar
Ghanem, M. A. et al. The role of polymer mechanochemistry in responsive materials and additive manufacturing. Nat. Rev. Mater. 6, 84–98 (2020).
Article Google Scholar
Duong, V. T. & Lin, C. C. Digital light processing 3D bioprinting of gelatin-norbornene hydrogel for enhanced vascularization. Macromol. Biosci. 23, 2300213 (2023).
Article Google Scholar
Nuñez Bernal, P. et al. Volumetric bioprinting of complex living-tissue constructs within seconds. Adv. Mater. 31, 1904209 (2019).
Article Google Scholar
Galarraga, J. H., Dhand, A. P., Enzmann, B. P. & Burdick, J. A. Synthesis, characterization, and digital light processing of a hydrolytically degradable hyaluronic acid hydrogel. Biomacromolecules 24, 413–425 (2023).
Article Google Scholar
Kim, S. H. et al. Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing. Nat. Commun. 9, 1620 (2018).
Article Google Scholar
Xie, M. et al. Volumetric additive manufacturing of pristine silk-based (bio)inks. Nat. Commun. 14, 210 (2023).
Article Google Scholar
Sakai, S. et al. Visible light-induced hydrogelation of an alginate derivative and application to stereolithographic bioprinting using a visible light projector and acid red. Biomacromolecules 19, 672–679 (2018).
Article Google Scholar
Zhang, J. et al. Water soluble photocurable carboxymethyl cellulose-based bioactive hydrogels for digital light processing. J. Appl. Polym. Sci. 139, 52155 (2022).
Article Google Scholar
Zanon, M. et al. Bioderived dyes-mediated vat photopolymerization 3D printing of chitosan hydrogels for tissue engineering. Addit. Manuf. 69, 103553 (2023).
Google Scholar
Kumari, S., Mondal, P. & Chatterjee, K. Digital light processing-based 3D bioprinting of κ-carrageenan hydrogels for engineering cell-loaded tissue scaffolds. Carbohydr. Polym. 290, 119508 (2022).
Article Google Scholar
Lian, L. et al. Rapid volumetric bioprinting of decellularized extracellular matrix bioinks. Adv. Mater. 36, e2304846 (2024).
Article Google Scholar
Kim, H. et al. Light-activated decellularized extracellular matrix-based bioinks for volumetric tissue analogs at the centimeter scale. Adv. Funct. Mater. 31, 2011252 (2021).
Article Google Scholar
Duong, V. T., Nguyen, H. D., Luong, N. H., Chang, C. Y. & Lin, C. C. Photo-responsive decellularized small intestine submucosa hydrogels. Adv. Funct. Mater. 34, 2401952 (2024).
Smith, P. T. et al. Methacrylated bovine serum albumin and tannic acid composite materials for three-dimensional printing tough and mechanically functional parts. ACS Appl. Mater. Interf. 14, 21418–21425 (2022).
Article Google Scholar
Muir, V. G. & Burdick, J. A. Chemically modified biopolymers for the formation of biomedical hydrogels. Chem. Rev. 121, 10908–10949 (2021).
Article Google Scholar
Kim, M. H. & Lin, C. C. Poly(ethylene glycol)-norbornene as a photoclick bioink for digital light processing 3D bioprinting. ACS Appl. Mater. Interf. 15, 2737–2746 (2022).
Article Google Scholar
Lim, K. S. et al. Bio-resin for high resolution lithography-based biofabrication of complex cell-laden constructs. Biofabrication 10, 034101 (2018).
Article Google Scholar
Ge, Q. et al. 3D printing of highly stretchable hydrogel with diverse UV curable polymers. Sci. Adv. 7, eaba4261 (2021).
Article Google Scholar
Xiang, Z., Li, N., Rong, Y., Zhu, L. & Huang, X. 3D-printed high-toughness double network hydrogels via digital light processing. Colloids Surf. A 639, 128329 (2022).
Article Google Scholar
Bao, Y. Recent trends in advanced photoinitiators for vat photopolymerization 3D printing. Macromol. Rapid Commun. 43, 2200202 (2022).
Article Google Scholar
Lim, K. S. et al. Visible light cross-linking of gelatin hydrogels offers an enhanced cell microenvironment with improved light penetration depth. Macromol. Biosci. 19, 1900098 (2019).
Article Google Scholar
Cook, C. C. et al. Highly tunable thiol-ene photoresins for volumetric additive manufacturing. Adv. Mater. 32, 2003376 (2020).
Article Google Scholar
Sun, Y. et al. Modeling the printability of photocuring and strength adjustable hydrogel bioink during projection-based 3D bioprinting. Biofabrication 13, 035032 (2021).
Article Google Scholar
Ma, Y. et al. Biomacromolecule-based agent for high-precision light-based 3D hydrogel bioprinting. Cell Rep. Phys. Sci. 3, 100985 (2022).
Article Google Scholar
Pritchard, Z. D. et al. Modeling and correcting cure-through in continuous stereolithographic 3D printing. Adv. Mater. Technol. 4, 1900700 (2019).
Article Google Scholar
Ligon, S. C., Husár, B., Wutzel, H., Holman, R. & Liska, R. Strategies to reduce oxygen inhibition in photoinduced polymerization. Chem. Rev. 114, 577–589 (2014).
Article Google Scholar
Emami, M. M. & Rosen, D. W. Modeling of light field effect in deep vat polymerization for grayscale lithography application. Addit. Manuf. 36, 101595 (2020).
Google Scholar
Saygin, V., Snapp, K., Gongora, A. E., Kolaghassi, R. & Brown, K. A. Mechanical consequences of oxygen inhibition in vat polymerization. Adv. Mater. Technol. 8, 2202022 (2023).
Article Google Scholar
You, S. et al. High cell density and high-resolution 3D bioprinting for fabricating vascularized tissues. Sci. Adv. 9, eade7923 (2023).
Article Google Scholar
Bernal, P. N. et al. Volumetric bioprinting of organoids and optically tuned hydrogels to build liver-like metabolic biofactories. Adv. Mater. 34, 2110054 (2022).
Article Google Scholar
Madrid-Wolff, J., Boniface, A., Loterie, D., Delrot, P. & Moser, C. Controlling light in scattering materials for volumetric additive manufacturing. Adv. Sci. 9, 2105144 (2022).
Article Google Scholar
Guan, J. et al. Compensating the cell-induced light scattering effect in light-based bioprinting using deep learning. Biofabrication 14, 015011 (2021).
Article Google Scholar
Liu, H. et al. Filamented light (FLight) biofabrication of highly aligned tissue-engineered constructs. Adv. Mater. 34, 2204301 (2022).
Article Google Scholar
Rizzo, R. et al. Multiscale hybrid fabrication: volumetric printing meets two-photon ablation. Adv. Mater. Technol. 8, 2201871 (2023).
Article Google Scholar
Caplins, B. W. et al. Characterizing light engine uniformity and its influence on liquid crystal display based vat photopolymerization printing. Addit. Manuf. 62, 103381 (2023).
Google Scholar
Caplins, B. W. et al. Influence of spectral bandwidth on the working curve in vat photopolymerization. Addit. Manuf. 85, 104172 (2024).
Google Scholar
Bennett, J. Measuring UV curing parameters of commercial photopolymers used in additive manufacturing. Addit. Manuf. 18, 203–212 (2017).
Google Scholar
Higgins, C. I., Brown, T. E. & Killgore, J. P. Digital light processing in a hybrid atomic force microscope: in situ, nanoscale characterization of the printing process. Addit. Manuf. 38, 101744 (2021).
Google Scholar
Li, Y. et al. Theoretical prediction and experimental validation of the digital light processing (DLP) working curve for photocurable materials. Addit. Manuf. 37, 101716 (2021).
Google Scholar
Uzcategui, A. C., Muralidharan, A., Ferguson, V. L., Bryant, S. J. & McLeod, R. R. Understanding and improving mechanical properties in 3D printed parts using a dual-cure acrylate-based resin for stereolithography. Adv. Eng. Mater. 20, 1800876 (2018).
Article Google Scholar
Saccone, M. A., Gallivan, R. A., Narita, K., Yee, D. W. & Greer, J. R. Additive manufacturing of micro-architected metals via hydrogel infusion. Nature 612, 685–690 (2022).
Article Google Scholar
David, S. et al. Co-culture approaches for cultivated meat production. Nat. Rev. Bioeng. 1, 817–831 (2023).
Article Google Scholar
Guzzi, E. A. & Tibbitt, M. W. Additive manufacturing of precision biomaterials. Adv. Mater. 32, 1901994 (2020).
Article Google Scholar
Goyanes, A., Det-Amornrat, U., Wang, J., Basit, A. W. & Gaisford, S. 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems. J. Control. Rel. 234, 41–48 (2016).
Article Google Scholar
Zhong, Z. et al. Rapid bioprinting of conjunctival stem cell micro-constructs for subconjunctival ocular injection. Biomaterials 267, 120462 (2021).
Article Google Scholar
He, B. et al. 3D printed biomimetic epithelium/stroma bilayer hydrogel implant for corneal regeneration. Bioact. Mater. 17, 234–247 (2022).
Google Scholar
Wang, Y. et al. 4D printed cardiac construct with aligned myofibers and adjustable curvature for myocardial regeneration. ACS Appl. Mater. Interf. 13, 12746–12758 (2021).
Article Google Scholar
Jiang, G. et al. A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model. Acta Biomater. 128, 150–162 (2021).
Article Google Scholar
Cianciosi, A. et al. Flexible allyl-modified gelatin photoclick resin tailored for volumetric bioprinting of matrices for soft tissue engineering. Adv. Healthc. Mater. 12, 2300977 (2023).
Article Google Scholar
Wang, M. et al. Molecularly cleavable bioinks facilitate high-performance digital light processing-based bioprinting of functional volumetric soft tissues. Nat. Commun. 13, 3317 (2022).
Article Google Scholar
Locke, R. C. et al. Linguistic analysis identifies emergent biomaterial fabrication trends for orthopaedic applications. Adv. Healthc. Mater. 12, 2202591 (2023).
Article Google Scholar
Dhand, A. P., Galarraga, J. H. & Burdick, J. A. Enhancing biopolymer hydrogel functionality through interpenetrating networks. Trends Biotechnol. 39, 519–538 (2021).
Article Google Scholar
Chaudhuri, O., Cooper-White, J., Janmey, P. A., Mooney, D. J. & Shenoy, V. B. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 584, 535–546 (2020).
Article Google Scholar
Xu, X. et al. Vat photopolymerization 3D printing for advanced drug delivery and medical device applications. J. Control. Rel. 329, 743–757 (2021).
Article Google Scholar
Bloomquist, C. J. et al. Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins. J. Control. Rel. 278, 9–23 (2018).
Article Google Scholar
Janusziewicz, R., Mecham, S. J., Olson, K. R. & Benhabbour, S. R. Design and characterization of a novel series of geometrically complex intravaginal rings with digital light synthesis. Adv. Mater. Technol. 5, 2000261 (2020).
Article Google Scholar
Wu, J. et al. Strong and ultra-tough supramolecular hydrogel enabled by strain-induced microphase separation. Adv. Funct. Mater. 33, 2210395 (2023).
Article Google Scholar
Mazari-Arrighi, E. et al. Self-organization of long-lasting human endothelial capillary-like networks guided by DLP bioprinting. Adv. Healthc. Mater. 13, 2302830 (2024).
Article Google Scholar
Zhu, W. et al. Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture. Biomaterials 124, 106–115 (2017).
Article Google Scholar
Franca, C. M. et al. High-throughput bioprinting of geometrically-controlled pre-vascularized injectable microgels for accelerated tissue regeneration. Adv. Healthc. Mater. 12, 2202840 (2023).
Article Google Scholar
Raman, R. et al. High-resolution projection microstereolithography for patterning of neovasculature. Adv. Healthc. Mater. 5, 610–619 (2016).
Article Google Scholar
Kinstlinger, I. S. et al. Perfusion and endothelialization of engineered tissues with patterned vascular networks. Nat. Protoc. 16, 3089–3113 (2021).
Article Google Scholar
Schoonraad, S. A. et al. Biomimetic and mechanically supportive 3D printed scaffolds for cartilage and osteochondral tissue engineering using photopolymers and digital light processing. Biofabrication 13, 044106 (2021).
Article Google Scholar
Tao, J. et al. Nanoparticle-stabilized emulsion bioink for digital light processing based 3D bioprinting of porous tissue constructs. Adv. Healthc. Mater. 11, 2102810 (2022).
Article Google Scholar
Ying, G. L. et al. Aqueous two-phase emulsion bioink-enabled 3D bioprinting of porous hydrogels. Adv. Mater. 30, 1805460 (2018).
Article Google Scholar
Ouyang, L. et al. Tunable microgel-templated porogel (MTP) bioink for 3D bioprinting applications. Adv. Healthc. Mater. 11, 2200027 (2022).
Article Google Scholar
Weber, P. et al. Microfluidic bubble-generator enables digital light processing 3D printing of porous structures. Aggregate 5, e409 (2024).
Article Google Scholar
Müller, M. Z. et al. Photoclick phase-separating hydrogels for 3D cell culture and volumetric bioprinting. Preprint at bioRxiv https://doi.org/10.1101/2022.01.29.478338 (2023).
Carberry, B. J. et al. 3D printing of sacrificial thioester elastomers using digital light processing for templating 3D organoid structures in soft biomatrices. Biofabrication 13, 044104 (2021).
Article Google Scholar
Kleger, N. et al. Light-based printing of leachable salt molds for facile shaping of complex structures. Adv. Mater. 34, 2203878 (2022).
Article Google Scholar
Koffler, J. et al. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Nat. Med. 25, 263–269 (2019).
Article Google Scholar
Hong, H. et al. Digital light processing 3D printed silk fibroin hydrogel for cartilage tissue engineering. Biomaterials 232, 119679 (2020).
Article Google Scholar
Chen, Y. et al. Noninvasive in vivo 3D bioprinting. Sci. Adv. 6, eaba7406 (2020).
Article Google Scholar
Urciuolo, A. et al. Intravital three-dimensional bioprinting. Nat. Biomed. Eng. 4, 901–915 (2020).
Article Google Scholar
Wu, J. et al. Biomechanically compatible hydrogel bioprosthetic valves. Chem. Mater. 34, 6129–6141 (2022).
Article Google Scholar
Liu, D. et al. Engineering tridimensional hydrogel tissue and organ phantoms with tunable springiness. Adv. Funct. Mater. 33, 2214885 (2023).
Article Google Scholar
Rodrigo-Navarro, A., Sankaran, S., Dalby, M. J., del Campo, A. & Salmeron-Sanchez, M. Engineered living biomaterials. Nat. Rev. Mater. 6, 1175–1190 (2021).
Article Google Scholar
Wangpraseurt, D. et al. Bionic 3D printed corals. Nat. Commun. 11, 1748 (2020).
Article Google Scholar
Binelli, M. R. et al. Complex living materials made by light-based printing of genetically programmed bacteria. Adv. Mater. 35, 2207483 (2023).
Article Google Scholar
Altin-Yavuzarslan, G., Sadaba, N., Brooks, S. M., Alper, H. S. & Nelson, A. Engineered living material bioreactors with tunable mechanical properties using vat photopolymerization. Small 35, e2306564 (2023).
Google Scholar
Altin-Yavuzarslan, G. et al. Additive manufacturing of engineered living materials with bio-augmented mechanical properties and resistance to degradation. Adv. Funct. Mater. 33, 2300332 (2023).
Article Google Scholar
Sugianto, W. et al. Gene expression dynamics in input-responsive engineered living materials programmed for bioproduction. Mater. Today Bio 20, 100677 (2023).
Article Google Scholar
Moroni, L. et al. Biofabrication strategies for 3D in vitro models and regenerative medicine. Nat. Rev. Mater. 3, 21–37 (2018).
Article Google Scholar
Loewa, A., Feng, J. J. & Hedtrich, S. Human disease models in drug development. Nat. Rev. Bioeng. 1, 545–559 (2023).
Article Google Scholar
Hu, Q. et al. 3D printed porous microgel for lung cancer cells culture in vitro. Mater. Des. 210, 110079 (2021).
Article Google Scholar
Ma, X. et al. Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proc. Natl Acad. Sci. USA 113, 2206–2211 (2016).
Article Google Scholar
Mao, Q. et al. Fabrication of liver microtissue with liver decellularized extracellular matrix (dECM) bioink by digital light processing (DLP) bioprinting. Mater. Sci. Eng. C 109, 110625 (2020).
Article Google Scholar
Ma, X. et al. Rapid 3D bioprinting of decellularized extracellular matrix with regionally varied mechanical properties and biomimetic microarchitecture. Biomaterials 185, 310–321 (2018).
Article Google Scholar
Liu, J. et al. Direct 3D bioprinting of cardiac micro-tissues mimicking native myocardium. Biomaterials 256, 120204 (2020).
Article Google Scholar
Zhou, X. et al. 3D bioprinting a cell-laden bone matrix for breast cancer metastasis study. ACS Appl. Mater. Interf. 8, 30017–30026 (2016).
Article Google Scholar
Gehlen, J., Qiu, W., Schädli, G. N., Müller, R. & Qin, X. H. Tomographic volumetric bioprinting of heterocellular bone-like tissues in seconds. Acta Biomater. 156, 49–60 (2023).
Article Google Scholar
Davidson, M. D. et al. Programmable and contractile materials through cell encapsulation in fibrous hydrogel assemblies. Sci. Adv. 7, 8157 (2021).
Article Google Scholar
Tang, M. et al. Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions. Cell Res. 30, 833–853 (2020).
Article Google Scholar
Tang, M. et al. Rapid 3D bioprinting of glioblastoma model mimicking native biophysical heterogeneity. Small 17, e2006050 (2021).
Article Google Scholar
Clevers, H. Modeling development and disease with organoids. Cell 165, 1586–1597 (2016).
Article Google Scholar
Gou, M. et al. Bio-inspired detoxification using 3D-printed hydrogel nanocomposites. Nat. Commun. 5, 3774 (2014).
Article Google Scholar
Zhu, Y., Sazer, D., Miller, J. S. & Warmflash, A. Rapid fabrication of hydrogel micropatterns by projection stereolithography for studying self-organized developmental patterning. PLoS ONE 16, e0245634 (2021).
Article Google Scholar
Leung, C. M. et al. A guide to the organ-on-a-chip. Nat. Rev. Meth. Prim. 2, 33 (2022).
Campbell, S. B. et al. Beyond polydimethylsiloxane: alternative materials for fabrication of organ-on-a-chip devices and microphysiological systems. ACS Biomater. Sci. Eng. 7, 2880–2899 (2021).
Article Google Scholar
Milton, L. A., Viglione, M. S., Ong, L. J. Y., Nordin, G. P. & Toh, Y. C. Vat photopolymerization 3D printed microfluidic devices for organ-on-a-chip applications. Lab Chip 23, 3537–3560 (2023).
Article Google Scholar
Karamzadeh, V., Shen, M. L., Lussier, F. & Juncker, D. Nanoporous, gas permeable PEGDA ink for 3D printingorgan‐on‐a‐chip devices. Adv. Function. Mater. 34, 2315035 (2024).
Article Google Scholar
Corbett, D. C. et al. Thermofluidic heat exchangers for actuation of transcription in artificial tissues. Sci. Adv. 6, 9062 (2020).
Article Google Scholar
Yafia, M. et al. Microfluidic chain reaction of structurally programmed capillary flow events. Nature 605, 464–469 (2022).
Article Google Scholar
Karamzadeh, V., Sohrabi-Kashani, A., Shen, M. & Juncker, D. Digital manufacturing of functional ready-to-use microfluidic systems. Adv. Mater. 35, 2303867 (2023).
Article Google Scholar
MacDonald, E. & Wicker, R. Multiprocess 3D printing for increasing component functionality. Science 353, aaf2093 (2016).
Article Google Scholar
Sampson, K. L. et al. Multimaterial vat polymerization additive manufacturing. ACS Appl. Polym. Mater. 3, 4304–4324 (2021).
Article Google Scholar
Kim, Y. T., Ahmadianyazdi, A. & Folch, A. A ‘print–pause–print’ protocol for 3D printing microfluidics using multimaterial stereolithography. Nat. Protoc. 2023 18:4 18, 1243–1259 (2023).
Google Scholar
Grigoryan, B. et al. Development, characterization, and applications of multi-material stereolithography bioprinting. Sci. Rep. 11, 1–13 (2021).
Article Google Scholar
Miri, A. K. et al. Microfluidics-enabled multimaterial maskless stereolithographic bioprinting. Adv. Mater. 30, 1800242 (2018).
Article Google Scholar
Han, D., Yang, C., Fang, N. X. & Lee, H. Rapid multi-material 3D printing with projection micro-stereolithography using dynamic fluidic control. Addit. Manuf. 27, 606–615 (2019).
Google Scholar
Choi, J. W., Kim, H. C. & Wicker, R. Multi-material stereolithography. J. Mater. Process. Technol. 211, 318–328 (2011).
Article Google Scholar
Bhusal, A. et al. Multi-material digital light processing bioprinting of hydrogel-based microfluidic chips. Biofabrication 14, 014103 (2021).
Article Google Scholar
Cheng, J. et al. Centrifugal multimaterial 3D printing of multifunctional heterogeneous objects. Nat. Commun. 13, 7931 (2022).
Article Google Scholar
Wang, M. et al. Digital light processing based bioprinting with composable gradients. Adv. Mater. 34, 2107038 (2022).
Article Google Scholar
Li, C., Ouyang, L., Armstrong, J. P. K. & Stevens, M. M. Advances in the fabrication of biomaterials for gradient tissue engineering. Trends Biotechnol. 39, 150–164 (2021).
Article Google Scholar
Chansoria, P. et al. Rationally designed anisotropic and auxetic hydrogel patches for adaptation to dynamic organs. Adv. Funct. Mater. 32, 2207590 (2022).
Chansoria, P. et al. Synergizing algorithmic design, photoclick chemistry and multi-material volumetric printing for accelerating complex shape engineering. Adv. Sci. 10, 2300912 (2023).
Article Google Scholar
Puiggalí-Jou, A. et al. FLight biofabrication supports maturation of articular cartilage with anisotropic properties. Adv. Healthc. Mater. 32, e2302179 (2023).
Google Scholar
Huang, J. et al. Conformal geometry and multimaterial additive manufacturing through freeform transformation of building layers. Adv. Mater. 33, 2005672 (2021).
Article Google Scholar
Ragelle, H. et al. Surface tension-assisted additive manufacturing. Nat. Commun. 9, 1184 (2018).
Article Google Scholar
Größbacher, G. et al. Volumetric printing across melt electrowritten scaffolds fabricates multi-material living constructs with tunable architecture and mechanics. Adv. Mater. 35, 2300756 (2023).
Article Google Scholar
Ribezzi, D. et al. Shaping synthetic multicellular and complex multimaterial tissues via embedded extrusion-volumetric printing of microgels. Adv. Mater. 35, 2301673 (2023).
Article Google Scholar
Tavares-Negrete, J. A. et al. A novel 3D-bioprinting technology of orderly extruded multi-materials via photopolymerization. Adv. Mater. Technol. 8, 2201926 (2023).
Article Google Scholar
Shanjani, Y., Pan, C. C., Elomaa, L. & Yang, Y. A novel bioprinting method and system for forming hybrid tissue engineering constructs. Biofabrication 7, 045008 (2015).
Article Google Scholar
Kunwar, P. et al. Hybrid laser printing of 3D, multiscale, multimaterial hydrogel structures. Adv. Opt. Mater. 7, 1900656 (2019).
Article Google Scholar
Yang, Y. et al. Biomimetic anisotropic reinforcement architectures by electrically assisted nanocomposite 3D printing. Adv. Mater. 29, 1605750 (2017).
Article Google Scholar
Martin, J. J., Fiore, B. E. & Erb, R. M. Designing bioinspired composite reinforcement architectures via 3D magnetic printing. Nat. Commun. 6, 8641 (2015).
Article Google Scholar
Paulsen, S. J. et al. Projection-based stereolithography for direct 3D printing of heterogeneous ultrasound phantoms. PLoS ONE 16, e0260737 (2021).
Article Google Scholar
Falandt, M. et al. Spatial-selective volumetric 4D printing and single-photon grafting of biomolecules within centimeter-scale hydrogels via tomographic manufacturing. Adv. Mater. Technol. 8, 2300026 (2023).
Article Google Scholar
Yu, C. et al. A sequential 3D bioprinting and orthogonal bioconjugation approach for precision tissue engineering. Biomaterials 258, 120294 (2020).
Article Google Scholar
Broguiere, N. et al. Morphogenesis guided by 3D patterning of growth factors in biological matrices. Adv. Mater. 32, 1908299 (2020).
Article Google Scholar
Batalov, I., Stevens, K. R. & DeForest, C. A. Photopatterned biomolecule immobilization to guide three-dimensional cell fate in natural protein-based hydrogels. Proc. Natl Acad. Sci. USA 118, e2014194118 (2021).
Article Google Scholar
Kunwar, P. et al. High-resolution 3D printing of stretchable hydrogel structures using optical projection lithography. ACS Appl. Mater. Interf. 12, 1640–1649 (2020).
Article Google Scholar
Brown, T. E. & Anseth, K. S. Spatiotemporal hydrogel biomaterials for regenerative medicine. Chem. Soc. Rev. 46, 6532–6552 (2017).
Article Google Scholar
Jiang, P. et al. Grayscale stereolithography of gradient hydrogel with site-selective shape deformation. Adv. Mater. Technol. 7, 2101288 (2022).
Article Google Scholar
Dong, M. et al. Digital light processing 3D printing of tough supramolecular hydrogels with sophisticated architectures as impact-absorption elements. Adv. Mater. 34, 2204333 (2022).
Article Google Scholar
Peng, X. et al. Multi-color 3D printing via single-vat grayscale digital light processing. Adv. Funct. Mater. 32, 2112329 (2022).
Article Google Scholar
Wang, B. et al. Stiffness control in dual color tomographic volumetric 3D printing. Nat. Commun. 13, 367 (2022).
Article Google Scholar
Lu, P. et al. Wavelength-selective light–matter interactions in polymer science. Matter 4, 2172–2229 (2021).
Article Google Scholar
Schwartz, J. J. & Boydston, A. J. Multimaterial actinic spatial control 3D and 4D printing. Nat. Commun. 10, 791 (2019).
Article Google Scholar
Kirillova, A., Maxson, R., Stoychev, G., Gomillion, C. T. & Ionov, L. 4D biofabrication using shape-morphing hydrogels. Adv. Mater. 29, 1703443 (2017).
Regehly, M. et al. Xolography for linear volumetric 3D printing. Nature 588, 620–624 (2020).
Article Google Scholar
Mainik, P. et al. DLP 4D printing of multi-responsive bilayered structures. Adv. Mater. Technol. 8, 2300727 (2023).
Article Google Scholar
Ahn, D., Stevens, L. M., Zhou, K. & Page, Z. A. Rapid high-resolution visible light 3D printing. ACS Cent. Sci. 6, 1555–1563 (2020).
Article Google Scholar
Truong, V. X., Tsang, K. M., Ercole, F. & Forsythe, J. S. Red light activation of tetrazine-norbornene conjugation for bioorthogonal polymer cross-linking across tissue. Chem. Mater. 29, 3678–3685 (2017).
Article Google Scholar
Tran, H. B. D. et al. 4D printing of adaptable “living” materials based on alkoxyamine chemistry. Adv. Funct. Mater. 34, 2315238 (2024).
Article Google Scholar
Liu, X., Liu, J., Lin, S. & Zhao, X. Hydrogel machines. Mater. Today 36, 102–124 (2020).
Article Google Scholar
Mishra, A. K. et al. Autonomic perspiration in 3D-printed hydrogel actuators. Sci Robot 5, eaaz3918 (2020).
Article Google Scholar
Hua, M. et al. 4D printable tough and thermoresponsive hydrogels. ACS Appl. Mater. Interf. 13, 12689–12697 (2021).
Article Google Scholar
Hu, Y. et al. Botanical-inspired 4D printing of hydrogel at the microscale. Adv. Funct. Mater. 30, 1907377 (2020).
Article Google Scholar
Aduba, D. C. et al. Vat photopolymerization 3D printing of acid-cleavable PEG-methacrylate networks for biomaterial applications. Mater. Today Commun. 19, 204–211 (2019).
Article Google Scholar
Ji, Z. et al. 3D printing of hydrogel architectures with complex and controllable shape deformation. Adv. Mater. Technol. 4, 1800713 (2019).
Article Google Scholar
Shiblee, N. I. et al. 4D printing of shape-memory hydrogels for soft-robotic functions. Adv. Mater. Technol. 4, 1900071 (2019).
Article Google Scholar
Zhao, Z. et al. Desolvation induced origami of photocurable polymers by digit light processing. Macromol. Rapid Commun. 38, 1600625 (2017).
Article Google Scholar
He, Y. et al. Digital light processing 4D printing of transparent, strong, highly conductive hydrogels. ACS Appl. Mater. Interf. 13, 36286–36294 (2021).
Article Google Scholar
Pruksawan, S., Lin, Z., Lee, Y. L., Chee, H. L. & Wang, F. K. 4D-printed hydrogel actuators through diffusion-path architecture design. ACS Appl. Mater. Interf. 15, 46388–46399 (2023).
Article Google Scholar
Odent, J. et al. Hierarchical chemomechanical encoding of multi-responsive hydrogel actuators via 3D printing. J. Mater. Chem. A 7, 15395–15403 (2019).
Article Google Scholar
Liu, B. et al. 4D printed hydrogel scaffold with swelling-stiffening properties and programmable deformation for minimally invasive implantation. Nat. Commun. 15, 1587 (2024).
Article Google Scholar
Zhao, X. et al. Soft materials by design: unconventional polymer networks give extreme properties. Chem. Rev. 121, 4309–4372 (2021).
Article Google Scholar
Webber, M. J. & Tibbitt, M. W. Dynamic and reconfigurable materials from reversible network interactions. Nat. Rev. Mater. 7, 541–556 (2022).
Article Google Scholar
Rizzo, R., Petelinšek, N., Bonato, A. & Zenobi-Wong, M. From free-radical to radical-free: a paradigm shift in light-mediated biofabrication. Adv. Sci. 10, 2205302 (2023).
Article Google Scholar
Nelson, B. R. et al. Photoinduced dithiolane crosslinking for multiresponsive dynamic hydrogels. Adv. Mater. https://doi.org/10.1002/adma.202211209 (2023).
Liu, A. P. et al. The living interface between synthetic biology and biomaterial design. Nat. Mater. 21, 390–397 (2022).
Article Google Scholar
Jorgensen, A. M., Yoo, J. J. & Atala, A. Solid organ bioprinting: strategies to achieve organ function. Chem. Rev. 120, 11093–11127 (2020).
Article Google Scholar
Murphy, S. V., De Coppi, P. & Atala, A. Opportunities and challenges of translational 3D bioprinting. Nat. Biomed. Eng. 4, 370–380 (2019).
Article Google Scholar
Ng, W. L. et al. Vat polymerization-based bioprinting—process, materials, applications and regulatory challenges. Biofabrication 12, 022001 (2020).
Article Google Scholar
Sarkar, N., Bhumiratana, S., Geris, L., Papantoniou, I. & Grayson, W. L. Bioreactors for engineering patient-specific tissue grafts. Nat. Rev. Bioeng. 1, 361–377 (2023).
Article Google Scholar
Wolf, K. J., Weiss, J. D., Uzel, S. G. M., Skylar-Scott, M. A. & Lewis, J. A. Biomanufacturing human tissues via organ building blocks. Cell Stem Cell 29, 667–677 (2022).
Article Google Scholar
Zheng, X. et al. Multiscale metallic metamaterials. Nat. Mater. 15, 1100–1106 (2016).
Article Google Scholar
Hwang, H. H. et al. High throughput direct 3D bioprinting in multiwell plates. Biofabrication 13, 025007 (2021).
Article Google Scholar
Kronenfeld, J. M., Rother, L., Saccone, M. A., Dulay, M. T. & DeSimone, J. M. Roll-to-roll, high-resolution 3D printing of shape-specific particles. Nature 627, 306–312 (2024).
Article Google Scholar
US FDA. Regulatory considerations for human cells, tissues, and cellular and tissue-based products: minimal manipulation and homologous use; https://www.fda.gov/regulatory-information/search-fda-guidance-documents/regulatory-considerations-human-cells-tissues-and-cellular-and-tissue-based-products-minimal (2020).
US FDA. Technical considerations for additive manufactured medical devices; https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-additive-manufactured-medical-devices (2017).
Fogarasi, M., Snodderly, K. L. & Di Prima, M. A. A survey of additive manufacturing trends for FDA-cleared medical devices. Nat. Rev. Bioeng. 1, 687–689 (2023).
Article Google Scholar
Wang, Z. et al. A simple and high-resolution stereolithography-based 3D bioprinting system using visible light crosslinkable bioinks. Biofabrication 7, 045009 (2015).
Article Google Scholar
Garciamendez-Mijares, C. E., Agrawal, P., García Martínez, G., Cervantes Juarez, E. & Zhang, Y. S. State-of-art affordable bioprinters: a guide for the DiY community. Appl. Phys. Rev. 8, 31312 (2021).
Article Google Scholar
Zhang, F. et al. The recent development of vat photopolymerization: a review. Addit. Manuf. 48, 102423 (2021).
Google Scholar
Li, W. et al. A smartphone-enabled portable digital light processing 3D printer. Adv. Mater. 33, 2102153 (2021).
Article Google Scholar
Zandrini, T., Florczak, S., Levato, R. & Ovsianikov, A. Breaking the resolution limits of 3D bioprinting: future opportunities and present challenges. Trends Biotechnol. 41, 604–614 (2023).
Article Google Scholar
Brown, T. E. et al. Voxel-scale conversion mapping informs intrinsic resolution in stereolithographic additive manufacturing. ACS Appl. Polym. Mater. 3, 290–298 (2021).
Article Google Scholar
Bliley, J. M., Shiwarski, D. J. & Feinberg, A. W. 3D-bioprinted human tissue and the path toward clinical translation. Sci. Transl. Med. 14, eabo7047 (2022).
Article Google Scholar
Doloff, J. C. et al. The surface topography of silicone breast implants mediates the foreign body response in mice, rabbits and humans. Nat. Biomed. Eng. 5, 1115–1130 (2021).
Article Google Scholar
Zhou, T. et al. 3D printable high-performance conducting polymer hydrogel for all-hydrogel bioelectronic interfaces. Nat. Mater. 22, 895–902 (2023).
Article Google Scholar
Zushin, P. J. H., Mukherjee, S. & Wu, J. C. FDA modernization Act 2.0: transitioning beyond animal models with human cells, organoids, and AI/ML-based approaches. J. Clin. Invest. 133, e175824 (2023).
Article Google Scholar
Download references
The authors acknowledge funding from the National Institutes of Health (R01HL160616, R01AR077362 and R01AR056624) and thank J. Killgore, T. Kolibaba, H. Zlotnick and B. Kirkpatrick for discussions and critical feedback on the manuscript.
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Abhishek P. Dhand & Jason A. Burdick
BioFrontiers Insstitute and Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado, USA
Matthew D. Davidson & Jason A. Burdick
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
A.P.D. researched data for the article and contributed to writing and editing the manuscript. M.D.D. contributed to discussion of content and writing. J.A.B. contributed to the discussion, reviewing and editing of the manuscript.
Correspondence to Jason A. Burdick.
The authors have submitted a provisional patent related to lithography-based printing of hydrogels.
Nature Reviews Bioengineering thanks the anonymous reviewer(s) for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
Reprints and permissions
Dhand, A.P., Davidson, M.D. & Burdick, J.A. Lithography-based 3D printing of hydrogels. Nat Rev Bioeng (2024). https://doi.org/10.1038/s44222-024-00251-9
Download citation
Published: 16 October 2024
DOI: https://doi.org/10.1038/s44222-024-00251-9
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative