Advancements and Applications of 4D Bioprinting in Biomedical Science

Hakan Eskizengin; Can Ergun

doi:10.1007/s10118-025-3259-0

Your Location：

Home >

Browse articles >

Advancements and Applications of 4D Bioprinting in Biomedical Science

REVIEW | Updated：2024-12-31

- Advancements and Applications of 4D Bioprinting in Biomedical Science
- Chinese Journal of Polymer Science Vol. 43, Issue 1, Pages: 18-39(2025)
- Affiliations：
  
  Department of Biology, Faculty of Science, Ankara University, Ankara 06560, Turkey
- Author bio：
  
  eskizengin@ankara.edu.tr
- Funds：
- DOI：10.1007/s10118-025-3259-0
  CLC：
- Published：01 January 2025，
  
  Published Online：25 December 2024，
  
  Received：14 August 2024，
  
  Revised：23 October 2024，
  
  Accepted：2024-10-27
- Accepted：
Scan QR Code
Eskizengin, H.; Ergun, C. Advancements and applications of 4D bioprinting in biomedical science. Chinese J. Polym. Sci. 2025, 43, 18–39

HAKAN ESKIZENGIN, CAN ERGUN. Advancements and Applications of 4D Bioprinting in Biomedical Science. [J]. Chinese journal of polymer science, 2025, 43(1): 18-39.
Eskizengin, H.; Ergun, C. Advancements and applications of 4D bioprinting in biomedical science. Chinese J. Polym. Sci. 2025, 43, 18–39 DOI： 10.1007/s10118-025-3259-0.

HAKAN ESKIZENGIN, CAN ERGUN. Advancements and Applications of 4D Bioprinting in Biomedical Science. [J]. Chinese journal of polymer science, 2025, 43(1): 18-39. DOI： 10.1007/s10118-025-3259-0.

摘要

4D bioprinting inherits the precision of 3D bioprinting but combines with the capabilities of post-fabrication transformation through smart materials that can change their physical or chemical properties by the introduction of some external triggers such as temperature

electricity

magnetic field

humidity

light

ions

reactive oxygen species

and molecules.

Abstract

The constraints of traditional 3D bioprinting are overcome by 4D bioprinting integrating with adaptable materials over time

resulting in dynamic

compliant

and functional biological structures. This innovative approach to bioprinting holds great promise for tissue engineering

regenerative medicine

and advanced drug delivery systems. 4D bioprinting is a technology that allows for the extension of 3D bioprinting technology by making predesigned structures change after they are fabricated using smart materials that can alter their characteristics

via

stimulus

leading to transformation in healthcare

which is able to provide precise personalized effective medical treatment without any side effects. This review article concentrates on some recent developments and applications in the field of 4D bioprinting

which can pave the way for groundbreaking advancements in biomedical sciences. 4D printing is a new chapter in bioprinting that introduces dynamism and functional living biological structures. Therefore

smart materials and sophisticated printing techniques can eliminate the challenges associated with printing complex organs and tissues. However

the problems with this process are biocompatibility

immunogenicity

and scalability

which need to be addressed. Moreover

numerous obstacles have been encountered during its widespread adoption in clinical practice. Therefore

4D bioprinting requires improvements in future material science innovations and further development in printers and manufacturing techniques to unlock its potential for better patient care and outcomes.

关键词

Keywords

Tissue engineeringFour-dimensional bioprintingThree-dimensional bioprintingHydrogelsStimuli sensitive polymers

references

Zhang, F.; Xia, Y.; Liu, Y.; Leng, J. Nano/microstructures of shape memory polymers: from materials to applications.Nanoscale Horizons2020,5, 1155−1173..

Bril, M.; Fredrich, S.; Kurniawan, N. A. Stimuli-responsive materials: a smart way to study dynamic cell responses.Smart Mater. Med.2022,3, 257−273..

Vydiam, K.; Mukherjee, S., Chapter 22 - 3D and 4D nanocomposites. InAdvances in Smart Nanomaterials and their Applications, Husen, A.; Siddiqi, K. S., Eds. Elsevier: 2023 ; pp. 505−522..

Pourmasoumi, P.; Moghaddam, A.; NematiMahand, S.; Heidari, F.; Salehi Moghaddam, Z.; Arjmand, M.; Kühnert, I.; Kruppke, B.; Wiesmann, H.-P.; Khonakdar, H. A. A review on the recent progress, opportunities, and challenges of 4D printing and bioprinting in regenerative medicine.J. Biomater. Sci. Polym. Ed.2023,34, 108−146..

Jiang, L.; Shen, Y.; Liu, Y.; Zhang, L.; Jiang, W. Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies.Theranostics2022,12, 1537−1556..

Sasai, Y. Next-generation regenerative medicine: organogenesis from stem cells in 3D culture.Cell Stem Cell2013,12, 520−530..

Jackson, E. L.; Lu, H. Three-dimensional models for studying development and disease: moving on from organisms to organs-on-a-chip and organoids.Integr. Biol.2016,8, 672−683..

Ren, L.; Li, B.; Liu, Q.; Ren, L.; Song, Z.; Zhou, X.; Gao, P. 4D printing dual stimuli-responsive bilayer structure toward multiple shape-shifting.Front. Mater.2021,8, 656180..

Willemen, N. G. A.; Morsink, M. A. J.; Veerman, D.; da Silva, C. F.; Cardoso, J. C.; Souto, E. B.; Severino, P. From oral formulations to drug-eluting implants: using 3D and 4D printing to develop drug delivery systems and personalized medicine.Bio-Design Manuf.2022,5, 85−106..

Tamo, A. K.; Djouonkep, L. D. W.; Selabi, N. B. S. 3D printing of polysaccharide-based hydrogel scaffolds for tissue engineering applications: a review.Int. J. Biological Macromol. 2024, 270, 132123..

Kangarshahi, B. M.; Naghib, S. M.; Kangarshahi, G. M.; Mozafari, M. R. Bioprinting of self-healing materials and nanostructures for biomedical applications: Recent advances and progresses on fabrication and characterization techniques.Bioprinting2024,38, e00335..

Wei, Q.; Wang, S.; Han, F.; Wang, H.; Zhang, W.; Yu, Q.; Liu, C.; Ding, L.; Wang, J.; Yu, L.; Zhu, C.; Li, B. Cellular modulation by the mechanical cues from biomaterials for tissue engineering.Biomater. Transl.2021,2, 323−342..

Hou, Y.; Yu, L.; Xie, W.; Camacho, L. C.; Zhang, M.; Chu, Z.; Wei, Q.; Haag, R. Surface roughness and substrate stiffness synergize to drive cellular mechanoresponse.Nano Lett.2020,20, 748−757..

Zarek, M.; Mansour, N.; Shapira, S.; Cohn, D. 4D printing of shape memory-based personalized endoluminal medical devices.Macromol. Rapid Commun. 2017, 38, 1600628..

Gnanakani, S. P. E.; Vijayalakshmi, R., Newer dimension: 4D- and 5D-printing opportunities in drug delivery to the skin. In3D Printing and Microfluidics in Dermatology, 2024 , CRC Press: pp. 157−190..

Shahbazi, M.; Jäger, H.; Ettelaie, R.; Mohammadi, A.; Asghartabar Kashi, P. Multimaterial 3D printing of self-assembling smart thermo-responsive polymers into 4D printed objects: a review.Additive Manufacturing2023,71, 103598..

Aldawood, F. K. A comprehensive review of 4D printing: state of the arts, opportunities, and challenges.Actuators 2023 ..

Kumar, P.; Suryavanshi, P.; Kumar Dwivedy, S.; Banerjee, S. Stimuli-responsive materials for 4D printing: mechanical, manufacturing, and biomedical applications.J. Mol. Liq.2024,410, 125553..

Gugulothu, S. B.; Chatterjee, K. Visible light-based 4D-bioprinted tissue scaffold.ACS Macro Lett.2023,12, 494−502..

Mandal, A.; Chatterjee, K. Emerging trends in humidity-responsive 4D bioprinting.Chem. Eng. J.2023,455, 140550..

Yang, Q.; Gao, B.; Xu, F. Recent advances in 4D bioprinting.Biotechnol. J.2020,15, 1900086..

Ashammakhi, N.; Ahadian, S.; Zengjie, F.; Suthiwanich, K.; Lorestani, F.; Orive, G.; Ostrovidov, S.; Khademhosseini, A. Advances and future perspectives in 4D bioprinting.Biotechnol. J.2018,13, 1800148..

Ergun, C. A current review on conducting polymer-based catalysts: advanced oxidation processes for the removal of aquatic pollutants.Water, Air, Soil Pollut.2023,234, 524..

Khoeini, R.; Nosrati, H.; Akbarzadeh, A.; Eftekhari, A.; Kavetskyy, T.; Khalilov, R.; Ahmadian, E.; Nasibova, A.; Datta, P.; Roshangar, L.; Deluca, D. C.; Davaran, S.; Cucchiarini, M.; Ozbolat, I. T. Natural and synthetic bioinks for 3D bioprinting.Adv. NanoBiomed. Res.2021,1, 2000097..

Vanaei, S.; Parizi, M. S.; Vanaei, S.; Salemizadehparizi, F.; Vanaei, H. R. An overview on materials and techniques in 3D bioprinting toward biomedical application.Eng. Reg.2021,2, 1−18..

Solis, D. M.; Czekanski, A. 3D and 4D additive manufacturing techniques for vascular-like structures – a review.Bioprinting 2022, 25, e00182..

Bartolo, P.; Malshe, A.; Ferraris, E.; Koc, B. 3D bioprinting: materials, processes, and applications.CIRP Annals 2022, 71, 577-597..

Das, H. R.; Uthaman, A.; Lal, H. M.; Babu, A.; Thomas, S., Chapter 12 - Shape memory polymers as sutures. InAdvanced Technologies and Polymer Materials for Surgical Sutures, Thomas, S.; Coates, P.; Whiteside, B.; Joseph, B.; Nair, K., Eds. Woodhead Publishing: 2023 ; pp. 265−281..

Yahia, L.Shape Memory Polymers for Biomedical Applications. 2015 , p. 1−310..

Xie, T. Tunable polymer multi-shape memory effect.Nature2010,464, 267−270..

Gopinath, S.; Adarsh, N. N.; Radhakrishnan Nair, P.; Mathew, S. Recent trends in thermo-responsive elastomeric shape memory polymer nanocomposites.Polym. Compos.2023,44, 4433−4458..

Zhao, W.; Yue, C.; Liu, L.; Liu, Y.; Leng, J. Research progress of shape memory polymer and 4D printing in biomedical application.Adv. Healthc. Mater.2023,12, 2201975..

Uyan, M.; Celiktas, M. S. Evaluation of the bio-based materials utilization in shape memory polymer composites production.Eur. Polym. J. 2023, 195..

Basak, S. Redesigning the modern applied medical sciences and engineering with shape memory polymers.Adv. Compos. Hybrid Mater.2021,4, 223−234..

Zhang, C.; Cai, D.; Liao, P.; Su, J. W.; Deng, H.; Vardhanabhuti, B.; Ulery, B. D.; Chen, S. Y.; Lin, J. 4D Printing of shape-memory polymeric scaffolds for adaptive biomedical implantation.Acta Biomater.2021,122, 101−110..

Li, Y. F.; Chen, Z. W.; Xie, Z. F.; Wang, S. S.; Xie, Y. M.; Zhang, Z. W. Recent development of biodegradable occlusion devices for intra-atrial shunts.RCM2024,25, 159..

Lin, C.; Huang, Z.; Wang, Q.; Zou, Z.; Wang, W.; Liu, L.; Liu, Y.; Leng, J. 4D printing of overall radiopaque customized bionic occlusion devices.Adv. Healthc. Mater. 2023, 12, 2201999..

Mahdavi, M.; Zolfaghari, A. Four-dimensional printing of continuous glass fiber-reinforced thermoplastics.Compos. Part B: Eng.2024,268, 111091..

Ben Abdallah, A.; Gamaoun, F.; Kallel, A.; Tcharkhtchi, A. Molecular weight influence on shape memory effect of shape memory polymer blend (poly(caprolactone)/styrene-butadiene-styrene).J. Appl. Polym. Sci.2021,138, 49761..

Liu, J.; Lu, H.; Fu, Y. Q. Yielding mechanisms for mechano-chemo-thermal couplings in amorphous shape memory polymer undergoing molecular entanglement.J. Phys. D: Appl. Phys.2021,54, 41..

Basak, S. Investigating entanglement-driven shape memory property: Insights and structure-property relationships from recent developments.Smart Mater. Meth.2024,1, 48−84..

Jerry Qi, H.; Castro, F.; Hermiller, J. M.; Havens, D. E. InOn the development of constitutive models of finite deformation behavior of shape memory polymers, International SAMPE Technical Conference, 2007 ..

Qi, H. J.; Dunn, M. L., Thermomechanical Behavior and Modeling Approaches. InShape-Memory Polymers and Multifunctional Composites, 2010 , CRC Press, pp. 65−90..

Wang, X.; Jian, W.; Lu, H.; Lau, D.; Fu, Y. Q. Selective entanglement coupling of nanoparticles in polymer nanocomposite with high shape recovery stress.Compos. Sci. Technol.2021,207, 108728..

Rahmatabadi, D.; Mirasadi, K.; Bayati, A.; Khajepour, M.; Ghasemi, I.; Baniassadi, M.; Abrinia, K.; Bodaghi, M.; Baghani, M. 4D printing thermo-magneto-responsive PETG-Fe3O4nanocomposites with enhanced shape memory effects.Appl. Mater. Today 2024, 40, 102361..

Chen, Y.; Mai, Y. W.; Ye, L. Perspectives for multiphase mechanical metamaterials.Mater. Sci. Eng.: R2023,153, 100725..

Ryan, K. R.; Down, M. P.; Banks, C. E. Future of additive manufacturing: overview of 4D and 3D printed smart and advanced materials and their applications.Chem. Eng. J.2021,403, 126162..

Bodaghi, M.; Namvar, N.; Yousefi, A.; Teymouri, H.; Demoly, F.; Zolfagharian, A. Metamaterial boat fenders with supreme shape recovery and energy absorption/dissipationviaFFF 4D printing.Smart Mater. Struct.2023,32, 095028..

Namvar, N.; Zolfagharian, A.; Vakili-Tahami, F.; Bodaghi, M. Reversible energy absorption of elasto-plastic auxetic, hexagonal, and AuxHex structures fabricated by FDM 4D printing.Smart Mater. Struct.2022,31, 055021..

Xu, P.; Lan, X.; Zeng, C.; Zhang, X.; Zhao, H.; Leng, J.; Liu, Y. Compression behavior of 4D printed metamaterials with various Poisson's ratios.Int. J. Mechan. Sci.2024,264, 108819..

Zhang, X.; Han, Y.; Zhu, M.; Chu, Y.; Li,W.; Zhang, Y.; Zhang, Y.; Luo, J.; Tao, R.; Qi, J. Bio-inspired 4D printed intelligent lattice metamaterials with tunable mechanical property.Int. J. Mechan. Sci.2024,272, 109198..

Lei, M.; Hong, W.; Zhao, Z.; Hamel, C.; Chen, M.; Lu, H.; Qi, H. J. 3D printing of auxetic metamaterials with digitally reprogrammable shape.ACS Appl. Mater. Interfaces2019,11, 22768−22776..

Yang, H.; D'Ambrosio, N.; Liu, P.; Pasini, D.; Ma, L. Shape memory mechanical metamaterials.Mater. Today2023,66, 36−49..

Roudbarian, N.; Jebellat, E.; Famouri, S.; Baniasadi, M.; Hedayati, R.; Baghani, M. Shape-memory polymer metamaterials based on triply periodic minimal surfaces.Eur. J. Mechanics, A/Solids2022,96, 104676..

Jolaiy, S.; Yousefi, A.; Hosseini, M.; Zolfagharian, A.; Demoly, F.; Bodaghi, M. Limpet-inspired design and 3D/4D printing of sustainable sandwich panels: pioneering supreme resiliency, recoverability and repairability.Appl. Mater. Today2024,38, 102243..

Munyensanga, P.; El Mabrouk, K. Design of bioinspired bone-based interpenetrating metamaterial with tailored mechanical properties.Smart Materi. Meth.2024,1, 167−199..

Yarali, E.; Klimopoulou, M.; David, K.; Boukany, P. E.; Staufer, U.; Fratila-Apachitei, L. E.; Zadpoor, A. A.; Accardo, A.; Mirzaali, M. J. Bone cell response to additively manufactured 3D micro-architectures with controlled Poisson's ratio: Auxetic vs. non-auxetic meta-biomaterials.Acta Biomater.2024,177, 228−242..

Darabi, M. A.; Khosrozadeh, A.; Mbeleck, R.; Liu, Y.; Chang, Q.; Jiang, J.; Cai, J.; Wang, Q.; Luo, G.; Xing, M. Skin-inspired multifunctional autonomic-intrinsic conductive self-healing hydrogels with pressure sensitivity, stretchability, and 3D printability.Adv. Mater.2017,29, 1700533..

Askari, M.; Afzali Naniz, M.; Kouhi, M.; Saberi, A.; Zolfagharian, A.; Bodaghi, M. Recent progress in extrusion 3D bioprinting of hydrogel biomaterials for tissue regeneration: a comprehensive review with focus on advanced fabrication techniques.Biomater. Sci.2021,9, 535−573..

Unagolla, J. M.; Jayasuriya, A. C. Hydrogel-based 3D bioprinting: A comprehensive review on cell-laden hydrogels, bioink formulations, and future perspectives.Appl. Mater. Today2020,18, 100479..

Ramiah, P.; du Toit, L. C.; Choonara, Y. E.; Kondiah, P. P. D.; Pillay, V. Hydrogel-based bioinks for 3D bioprinting in tissue.Front. Mater.2020,7, 76..

Isik, M.; Karakaya, E.; Arslan, T. S.; Atila, D.; Erdogan, Y. K.; Arslan, Y. E.; Eskizengin, H.; Eylem, C. C.; Nemutlu, E.; Ercan, B.; D'Este, M.; Okesola, B. O.; Derkus, B. 3D printing of extracellular matrix-based multicomponent, all-natural, highly elastic, and functional materials toward vascular tissue engineering.Adv. Healthc. Mater.2023,12, 2203044..

Ozbolat, I. T.; Hospodiuk, M. Current advances and future perspectives in extrusion-based bioprinting.Biomaterials2016,76, 321−343..

Falahati, M.; Ahmadvand, P.; Safaee, S.; Chang, Y. C.; Lyu, Z.; Chen, R.; Li, L.; Lin, Y. Smart polymers and nanocomposites for 3D and 4D printing.Mater. Today2020,40, 215−245..

Liu, H.; Xing, F.; Yu, P.; Zhe, M.; Duan, X.; Liu, M.; Xiang, Z.; Ritz, U. A review of biomacromolecule-based 3D bioprinting strategies for structure-function integrated repair of skin tissues.Int. J. Biol. Macromol.2024,268, 131623..

Megdich, A.; Habibi,M.; Laperrière, L. A review on 4D printing: material structures, stimuli and additive manufacturing techniques.Mater. Lett.2023,337, 133977..

Gudapati, H.; Dey, M.; Ozbolat, I. A comprehensive review on droplet-based bioprinting: past, present and future.Biomaterials2016,102, 20−42..

Suryatal, B. K.; Sarawade, S. S.; Deshmukh, S. P. Fabrication of medium scale 3D components using a stereolithography system for rapid prototyping.Journal of King Saud University - Engineering Sciences2023,35, 40−52..

Raman, R.; Bashir, R., Chapter 6 - Stereolithographic 3D Bioprinting for Biomedical Applications. InEssentials of 3D Biofabrication and Translation, Atala, A.; Yoo, J. J., Eds. Academic Press: Boston, 2015 ; pp 89−121..

Wang, Z.; Abdulla, R.; Parker, B.; Samanipour, R.; Ghosh, S.; Kim, K. A simple and high-resolution stereolithography-based 3D bioprinting system using visible light crosslinkable bioinks.Biofabrication2015,7, 045009..

Miao, S.; Cui, H.; Nowicki, M.; Xia, L.; Zhou, X.; Lee, S.-J.; Zhu, W.; Sarkar, K.; Zhang, Z.; Zhang, L. G. Stereolithographic 4D bioprinting of multiresponsive architectures for neural engineering.Adv. Biosystems2018,2, 1800101..

Zu, S.; Wang, Z.; Zhang, S.; Guo, Y.; Chen, C.; Zhang, Q.; Wang, Z.; Liu, T.; Liu, Q.; Zhang, Z. A bioinspired 4D printed hydrogel capsule for smart controlled drug release.Mater. Today Chem.2022,24, 100789..

Nizioł, M.; Paleczny, J.; Junka, A.; Shavandi, A.; Dawiec-Liśniewska, A.; Podstawczyk, D. 3D printing of thermoresponsive hydrogel laden with an antimicrobial agent towards wound healing applications.Bioengineering,2021,8, 79..

Bozuyuk, U.; Yasa, O.; Yasa, I. C.; Ceylan, H.; Kizilel, S.; Sitti, M. Light-triggered drug release from 3D-printed magnetic chitosan microswimmers.ACS Nano2018,12, 9617−9625..

Wei, H.; Zhang, Q.; Yao, Y.; Liu, L.; Liu, Y.; Leng, J. Direct-write fabrication of 4D active shape-changing structures based on a shape memory polymer and its nanocomposite.ACS Appl. Mater. Interfaces2017,9, 876−883..

Ding, A.; Lee, S. J.; Ayyagari, S.; Tang, R.; Huynh, C. T.; Alsberg, E. 4D biofabricationviainstantly generated graded hydrogel scaffolds.Bioact. Mater. 2022, 7, 324-332..

Lin, C.; Zhang, L.; Liu, Y.; Liu, L.; Leng, J. 4D printing of personalized shape memory polymer vascular stents with negative Poisson’s ratio structure: a preliminary study.Sci. China Technol. Sci.2020,63, 578−588..

Cui, H.; Liu, C.; Esworthy, T.; Huang, Y.; Yu, Z. X.; Zhou, X.; San, H.; Lee, S. J.; Hann, S. Y.; Boehm, M.; Mohiuddin, M.; Fisher, J. P.; Zhang, L. G. 4D physiologically adaptable cardiac patch: a 4-monthin vivostudy for the treatment of myocardial infarction.Sci. Adv.2020,6, eabb5067..

Cui, C.; Kim, D.-O.; Pack, M. Y.; Han, B.; Han, L.; Sun, Y.; Han, L. H. 4D printing of self-folding and cell-encapsulating 3D microstructures as scaffolds for tissue-engineering applications.Biofabrication2020,12, 045018..

Cui, H.; Miao, S.; Esworthy, T.; Lee, S.-j.; Zhou, X.; Hann, S. Y.; Webster, T. J.; Harris, B. T.; Zhang, L. G. A novel near-infrared light responsive 4D printed nanoarchitecture with dynamically and remotely controllable transformation.Nano Res.2019,12, 1381−1388..

He, W.; Zhou, D.; Gu, H.; Qu, R.; Cui, C.; Zhou, Y.; Wang, Y.; Zhang, X.; Wang, Q.; Wang, T.; Zhang, Y. A biocompatible 4D printing shape memory polymer as emerging strategy for fabrication of deployable medical devices.Macromol. Rapid Commun.2023,44, 2200553..

Wang, Y.; Miao, Y.; Zhang, J.; Wu, J. P.; Kirk, T. B.; Xu, J.; Ma, D.;Xue, W. Three-dimensional printing of shape memory hydrogels with internal structure for drug delivery.Mater. Sci. Eng.: C2018,84, 44−51..

Murphy, S. V.; Atala, A. 3D bioprinting of tissues and organs.Nat. Biotechnol. 2014, 32, 773-785..

Kabirian, F.; Mela, P.; Heying, R. 4D printing applications in the development of smart cardiovascular implants.Front. Bioeng. Biotechnol. 2022, 10..

Douillet, C.; Nicodeme, M.; Hermant, L.; Bergeron, V.; Guillemot, F.; Fricain, J.-C.; Oliveira, H.; Garcia, M. From local to global matrix organization by fibroblasts: a 4D laser-assisted bioprinting approach.Biofabrication2022,14, 025006..

Díaz-Payno, P. J.; Kalogeropoulou, M.; Muntz, I.; Kingma, E.; Kops, N.; D'Este, M.; Koenderink, G. H.; Fratila-Apachitei, L. E.; van Osch, G. J. V. M.; Zadpoor, A. A. Swelling-dependent shape-based transformation of a human mesenchymal stromal cells-laden 4d bioprinted construct for cartilage tissue engineering.Adv. Healthc. Mater.2023,12, 2201891..

Ding, A.; Jeon, O.; Cleveland, D.; Gasvoda, K. L.; Wells, D.; Lee, S. J.; Alsberg, E. Jammed micro-flake hydrogel for four-dimensional living cell bioprinting.Adv. Mater.2022,34, 2109394..

Miao, S.; Cui, H.; Esworthy, T.; Mahadik, B.; Lee, S.-j.; Zhou, X.; Hann, S. Y.; Fisher, J. P.; Zhang, L. G. 4D self-morphing culture substrate for modulating cell differentiation.Adv. Sci. 2020, 7, 1902403..

Kim, S. H.; Seo, Y. B.; Yeon, Y. K.; Lee, Y. J.; Park, H. S.; Sultan, M. T.; Lee, J. M.; Lee, J. S.; Lee, O. J.; Hong, H.; Lee, H.; Ajiteru, O.; Suh, Y. J.; Song, S. H.; Lee, K. H.; Park, C. H. 4D-bioprinted silk hydrogels for tissue engineering.Biomaterials 2020, 260, 120281..

Santos, A.; Bakker, A. D.; Klein-Nulend, J. The role of osteocytes in bone mechanotransduction.Osteoporosis International2009,20, 1027−1031..

Jeong, S. I.; Kwon, J. H.; Lim, J. I.; Cho, S. W.; Jung, Y.; Sung, W. J.; Kim, S. H.; Kim, Y. H.; Lee, Y. M.; Kim, B. S.; Choi, C. Y.; Kim, S. J. Mechano-active tissue engineering of vascular smooth muscle using pulsatile perfusion bioreactors and elastic PLCL scaffolds.Biomaterials2005,26, 1405−1411..

Santos, L. J.; Reis, R. L.; Gomes, M. E. Harnessing magnetic-mechano actuation in regenerative medicine and tissue engineering.Trends Biotechnol.2015,33, 471−479..

Dessì, M.; Borzacchiello, A.; Mohamed, T. H. A.; Abdel-Fattah, W. I.; Ambrosio, L. Novel biomimetic thermosensitiveβ-tricalcium phosphate/chitosan-based hydrogels for bone tissue engineering.J. Biomed. Mater. Res. Part A2013,101, 2984−2993..

Yang, G. H.; Kim, W.; Kim, J.; Kim, G. A skeleton muscle model using GelMA-based cell-aligned bioink processed with an electric-field assisted 3D/4D bioprinting.Theranostics2021,11, 48−63..

Liu, X.; Zhao, K.; Gong, T.; Song, J.; Bao, C.; Luo, E.; Weng, J.; Zhou, S. Delivery of growth factors using a smart porous nanocomposite scaffold to repair a mandibular bone defect.Biomacromolecules2014,15, 1019−1030..

Zhang, J.; Zhao, S.; Zhu, M.; Zhu, Y.; Zhang, Y.; Liu, Z.; Zhang, C. 3D-printed magnetic Fe3O4/MBG/PCL composite scaffolds with multifunctionality of bone regeneration, local anticancer drug delivery and hyperthermia.J. Mater. Chem. B 2014, 2, 7583-7595..

Xu, Y.; Han, J.; Chai, Y.; Yuan, S.; Lin, H.; Zhang, X. Development of porous chitosan/tripolyphosphate scaffolds with tunable uncross-linking primary amine content for bone tissue engineering.Mater. Sci. Eng.: C2018,85, 182−190..

Hann, S. Y.; Cui, H.; Esworthy, T.; Zhang, L. G. 4D thermo-responsive smart hiPSC-CM Cardiac construct for myocardial cell therapy.Int. J. Nanomed.2023,18, 1809−1821..

Miao, S.; Zhu, W.; Castro, N. J.; Nowicki, M.; Zhou, X.; Cui, H.; Fisher, J. P.; Zhang, L. G. 4D printing smart biomedical scaffolds with novel soybean oil epoxidized acrylate.Sci. Rep.2016,6, 27226..

Miao, S.; Cui, H.; Nowicki, M.; Lee, S. J.; Almeida, J.; Zhou, X.; Zhu, W.; Yao, X.; Masood, F.; Plesniak, M. W.; Mohiuddin, M.; Zhang, L. G. Photolithographic-stereolithographic-tandem fabrication of 4D smart scaffolds for improved stem cell cardiomyogenic differentiation.Biofabrication2018,10, 035007..

Faber, L.; Yau, A.; Chen, Y. Translational biomaterials of four-dimensional bioprinting for tissue regeneration.Biofabrication2024,16, 012001..

Dong, S. L.; Han, L.; Du, C. X.; Wang, X. Y.; Li, L. H.; Wei, Y. 3D printing of aniline tetramer-grafted-polyethylenimine and pluronic F127 composites for electroactive scaffolds.Macromol. Rapid Commun.2017,38, 1600551..

Wang, Y.; Cui, H.; Wang, Y.; Xu, C.; Esworthy, T. J.; Hann, S. Y.; Boehm, M.; Shen, Y. L.; Mei, D.; Zhang, L. G. 4D printed cardiac construct with aligned myofibers and adjustable curvature for myocardial regeneration.ACS Appl. Mater. Interfaces2021,13, 12746−12758..

Hegde, S.; Hsiao, A. Improving the Fontan: Pre-surgical planning using four dimensional (4D) flow, bio-mechanical modeling and three dimensional (3D) printing.Prog. Pediatr. Cardiol.2016,43, 57−60..

Morrison, R. J.; Hollister, S. J.; Niedner, M. F.; Mahani, M. G.; Park, A. H.; Mehta, D. K.; Ohye, R. G.; Green, G. E. Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients.Sci. Transl. Med.2015,7, 285ra64..

Mahjoubnia, A.; Cai, D.; Wu, Y.; King, S. D.; Torkian, P.; Chen, A. C.; Talaie, R.; Chen, S. Y.; Lin, J. Digital light 4D printing of bioresorbable shape memory elastomers for personalized biomedical implantation.Acta Biomater.2024,177, 165−177..

Esworthy, T. J.; Miao, S.; Lee, S. J.; Zhou, X.; Cui, H.; Zuo, Y. Y.; Zhang, L. G. Advanced 4D-bioprinting technologies for brain tissue modeling and study.Int. J. Smart Nano Mater.2019,10, 177−204..

Shahbazi, M.; Jäger, H.; Ettelaie, R.; Chen, J.; Mohammadi, A.; Kashi, P. A.; Ulbrich, M. A smart thermoresponsive macroporous 4D structure by 4D printing of Pickering-high internal phase emulsions stabilized by plasma-functionalized starch nanomaterials for a possible delivery system.Current Res. Food Sci.2024,8, 100686..

Cui, H.; Zhu, W.; Miao, S.; Sarkar, K.; Zhang, L. G. 4D printed nerve conduit with in situ neurogenic guidance for nerve regeneration.Tissue Engineering Part A2023,30, 293−303..

Joshi, A.; Choudhury, S.; Baghel, V. S.; Ghosh, S.; Gupta, S.; Lahiri, D.; Ananthasuresh, G. K.; Chatterjee, K. 4D printed programmable shape-morphing hydrogels as intraoperative self-folding nerve conduits for sutureless neurorrhaphy.Adv. Healthc. Mater.2023,12, 2300701..

Lu, Z.; Cui, J.; Liu, F.; Liang, C.; Feng, S.; Sun, Y.; Gao, W.; Guo, Y.; Zhang, B.; Huang, W. A 4D printed adhesive, thermo-contractile, and degradable hydrogel for diabetic wound healing.Adv. Healthc. Mater.2024,13, 2303499..

Wang, Z.; Jiang, C.; Fan, Y.; Hao, X.; Dong, Y.; He, X.; Gao, J.; Zhang, Y.; Li, M.; Wang, M.; Liu, Y.; Xu, W. The application of a 4D-printed chitosan-based stem cell carrier for the repair of corneal alkali burns.Stem Cell. Res. Ther.2024,15, 41..

Wang, M.; Liu, K.; Wang, X.; Shang, Z.; Liu, Y.; Pan, N.; Sun, X.; Xu, W. Limbal stem cells carried by a four-dimensional-printed chitosan-based scaffold for corneal epithelium injury in diabetic rabbits.Front. Physiol.2024,15, 1285850..

Amukarimi, S.; Rezvani, Z.; Eghtesadi, N.; Mozafari, M. Smart biomaterials: from 3D printing to 4D bioprinting.Methods2022,205, 191−199..

Costa, P. D. C.; Costa, D. C. S.; Correia, T. R.; Gaspar, V. M.; Mano, J. F. Natural origin biomaterials for 4D bioprinting tissue-like constructs.Adv. Mater. Technol.2021,6, 2100168..

Mirani, B.; Pagan, E.; Currie, B.; Siddiqui, M. A.; Hosseinzadeh, R.; Mostafalu, P.; Zhang, Y. S.; Ghahary, A.; Akbari, M. An advanced multifunctional hydrogel-based dressing for wound monitoring and drug delivery.Adv. Healthc. Mater.2017,6, 1700718..

Okwuosa, T. C.; Pereira, B. C.; Arafat, B.; Cieszynska, M.; Isreb, A.; Alhnan, M. A. Fabricating a shell-core delayed release tablet using dual FDM 3D printing for patient-centred therapy.Pharm. Res.2017,34, 427−437..

Zhang, Y.; Raza, A.; Xue, Y. Q.; Yang, G.; Hayat, U.; Yu, J.; Liu, C.; Wang, H. J.; Wang, J. Y. Water-responsive 4D printing based on self-assembly of hydrophobic protein “Zein” for the control of degradation rate and drug release.Bioact. Mater.2023,23, 343−352..

Luthfikasari, R.; Patil, T. V.; Patel, D. K.; Dutta, S. D.; Ganguly, K.; Espinal, M. M.; Lim, K. T. Plant-actuated micro-nanorobotics platforms: structural designs, functional prospects, and biomedical applications.Small2022,18, 2201417..

Zhang, Y.; Zhang, L.; Yang, L.; Vong, C. I.; Chan, K. F.; Wu, W. K. K.; Kwong, T. N. Y.; Lo, N. W. S.; Ip, M.; Wong, S. H.; Sung, J. J. Y.; Chiu, P. W. Y.; Zhang, L. Real-time tracking of fluorescent magnetic spore–based microrobots for remote detection ofC. difftoxins.Sci. Adv.2019,5, eaau9650..

Gao, W.; Feng, X.; Pei, A.; Kane, C. R.; Tam, R.; Hennessy, C.; Wang, J. Bioinspired helical microswimmers based on vascular plants.Nano Lett.2014,14, 305−310..

Chen, Y.; Li, M.; Tang, Q.; Cheng, Y.; Miao, A.; Cheng, L.; Zhu, S.; Luo, T.; Liu, G.; Zhang, L.; Niu, F.; Zhao, L.; Chen, J.; Yang, R. High-speed NIR-driven untethered 3D-printed hydrogel microrobots in high-viscosity liquids.Adv. Intelligent Systems2023,5, 2200311..

Rajabasadi, F.; Moreno, S.; Fichna, K.; Aziz, A.; Appelhans, D.; Schmidt, O. G.; Medina-Sánchez, M. Multifunctional 4D-printed sperm-hybrid microcarriers for assisted reproduction.Adv. Mater.2022,34, 2204257..

Rahimnejad, M.; Jahangiri, S.; Zirak Hassan Kiadeh, S.; Rezvaninejad, S.; Ahmadi, Z.; Ahmadi, S.; Safarkhani, M.; Rabiee, N. Stimuli-responsive biomaterials: smart avenue toward 4D bioprinting.Crit. Rev. Biotechnol.2024,44, 860−891..

Ghazal, A. F.; Zhang, M.; Liu, Z. Spontaneous color change of 3D printed healthy food product over time after printing as a novel application for 4D food printing.Food Bioproc. Technol.2019,12, 1627−1645..

Ren, L.; Wu, Q.; Liu, Q.; Hao, P.; Tang, J.; Li, J.; He, Y.; Wang, K.; Ren, L.; Zhou, X.; Li, B.; Liu, H. Stiffness-tunable and self-sensing integrated soft machines based on 4D printed conductive shape memory composites.Mater. Design2023,228, 111851..

Avinash, K.; Patolsky, F. Laser-induced graphene structures: from synthesis and applications to future prospects.Mater. Today2023,70, 104−136..

Lai, Y. C.; Wu, H. M.; Lin, H. C.; Chang, C. L.; Chou, H. H.; Hsiao, Y. C.; Wu, Y. C. Entirely, intrinsically, and autonomously self-healable, highly transparent, and superstretchable triboelectric nanogenerator for personal power sources and self-powered electronic skins.Adv. Funct. Mater.2019,29, 1904626..

Shao, B.; Lu, M. H.; Wu, T. C.; Peng, W. C.; Ko, T. Y.; Hsiao, Y. C.; Chen, J. Y.; Sun, B.; Liu, R.; Lai, Y. C. Large-area, untethered, metamorphic, and omnidirectionally stretchable multiplexing self-powered triboelectric skins.Nat. Commun.2024,15, 1238..

Xu, W.; Huang, L. B.; Hao, J. Fully self-healing and shape-tailorable triboelectric nanogenerators based on healable polymer and magnetic-assisted electrode.Nano Energy2017,40, 399−407..

Huang, L. B.; Han, J. C.; Chen, S.; Sun, Z.; Dai, X.; Ge, P.; Zhao, C. H.; Zheng, Q. Q.; Sun, F. C.; Hao, J. 4D-printed self-recovered triboelectric nanogenerator for energy harvesting and self-powered sensor.Nano Energy2021,84, 105873..

Jo, S. E.; Kim, M. K.; Kim, M. S.; Kim, Y. J. Flexible thermoelectric generator for human body heat energy harvesting.Electronics Lett.2012,48, 1015−1017..

Liu, H.; Wang, Y.; Mei, D.; Shi, Y.; Chen, Z. InDesign of a wearable thermoelectric generator for harvesting human body energy, Lecture Notes in Electrical Engineering, 2017 ; pp. 55−66..

Kiziroglou, M. E.; Wright, S. W.; Shi, M.; Boyle, D. E.; Becker, T.; Evans, J. W.; Yeatman, E. M. Milliwatt Power Supply by Dynamic Thermoelectric Harvesting.Journal of Physics: Conference Series2019,1407, 012098..

Schönfeld, D.; Walter, M.; Teicht, C.; Walter, M.; Rümmler, T.; Pretsch, T. Self-regulating thermal energy storage device.Smart Mater. Meth.2024,1, 3−29..

Geiss, M. J.; Boddeti, N.; Weeger, O.; Maute, K.; Dunn, M. L. Combined level-set-XFEM-density topology optimization of four-dimensional printed structures undergoing large deformation.J. Mechan. Design2019,141, 4041945..

Pivar, M.; Muck, D. InStudy of 4D primitives' self-transformation, International Symposium on Graphic Engineering and Design, 2020 ; pp. 515−523..

Suriano, R.; Bernasconi, R.; Magagnin, L.; Levi, M. 4D printing of smart stimuli-responsive polymers.J. Electrochem. Soc.2019,166, B3274−B3281..

Bodaghi, M.; Zolfagharian, A., 4D printing principles and manufacturing. InSmart Materials in Additive Manufacturing, volume 1: 4D Printing Principles and Fabrication, 2022 ; pp. 1−17..

Noroozi, R.; Arif,Z. U.; Taghvaei, H.; Khalid, M. Y.; Sahbafar, H.; Hadi, A.; Sadeghianmaryan, A.; Chen, X. 3D and 4D bioprinting technologies: a game changer for the biomedical sector?Ann. Biomed. Eng.2023,51, 1683−1712..

Mota, C.; Camarero-Espinosa, S.; Baker, M. B.; Wieringa, P.; Moroni, L. Bioprinting: from tissue and organ development toin vitromodels.Chem. Rev.2020,120, 10547−10607..

Maharjan, S.; Bonilla, D.; Zhang, Y. S. Strategies towards kidney tissue biofabrication.Curr. Opin. Biomed. Eng.2022,21, 100362..

Nguyen, A. K.; Goering, P. L.; Reipa, V.; Narayan, R. J. Toxicity and photosensitizing assessment of gelatin methacryloyl-based hydrogels photoinitiated with lithium phenyl-2,4,6-trimethylbenzoylphosphinate in human primary renal proximal tubule epithelial cells.Biointerphases2019,14, 021007..

Dutta, S. D.; Patil, T. V.; Ganguly, K.; Randhawa, A.; Lim, K. T. Unraveling the potential of 3D bioprinted immunomodulatory materials for regulating macrophage polarization: state-of-the-art in bone and associated tissue regeneration.Bioact. Mater.2023,28, 284−310..

Wu, P.; Shen, L.; Liu, H. F.; Zou, X. H.; Zhao, J.; Huang, Y.; Zhu, Y. F.; Li, Z. Y.; Xu, C.; Luo, L. H.; Luo, Z. Q.; Wu, M. H.; Cai, L.; Li, X. K.; Wang, Z. G. The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine.Military Medical Research2023,10, 35..

Liu, X.; Chen, W.; Shao, B.; Zhang, X.; Wang, Y.; Zhang, S.; Wu, W. Mussel patterned with 4D biodegrading elastomer durably recruits regenerative macrophages to promote regeneration of craniofacial bone.Biomaterials2021,276, 120998..

Aggarwal, S.; Hakovirta, M., New Industrial Sustainable Growth: 3D and 4D Printing. InTrends and Opportunities of Rapid Prototyping Technologies, Răzvan, P., Ed. IntechOpen: Rijeka, 2022 ; Ch. 2..

Paz, R.; Pei, E.; Monzón, M.; Ortega, F.; Suárez, L. Lightweight parametric design optimization for 4D printed parts.Integrated Computer-Aided Engineering2017,24, 225−240..

Espino, M. T.; Tuazon, B. J.; Espera, A. H.; Nocheseda, C. J. C.; Manalang, R. S.; Dizon, J. R. C.; Advincula, R. C. Statistical methods for design and testing of 3D-printed polymers.MRS Commun.2023,13, 193−211..

Jin, L.; Zhai, X.; Jiang, J.; Zhang, K.; Liao, W. H. InOptimizing stimuli-based 4D printed structures: a paradigm shift in programmable material response, Proceedings of SPIE - The International Society for Optical Engineering, 2024 ..

Su, J. W.; Li, D.; Xie, Y.; Zhou, T.; Gao, W.; Deng, H.; Xin, M.; Lin, J. A machine learning workflow for 4D printing: understand and predict morphing behaviors of printed active structures.Smart Mater. Struct.2020,30, 1..

Han, M.; Yang, Y.; Li, L. Techno-economic modeling of 4D printing with thermo-responsive materials towards desired shape memory performance.IISE Transactions2022,54, 1047−1059..

Mehrabi, O.; Sabri, H.; Karamimoghadam, M.; Khoran, M.; Casalino, G.; Moradi, M. Statistical and experimental study on additive manufacturing of polyethylene terephthalate glycol using fused deposition modeling.Smart Materials & Methods2024,1, 119−139..

Rahmatabadi, D.; Soltanmohammadi, K.; Pahlavani, M.; Aberoumand, M.; Soleyman, E.; Ghasemi, I.; Baniassadi, M.; Abrinia, K.; Bodaghi, M.; Baghani, M. Shape memory performance assessment of FDM 3D printed PLA-TPU composites by Box-Behnken response surface methodology.Int. J. Adv. Manuf. Technol.2023,127, 935−950..

Jin, L.; Zhai, X.; Wang, K.; Zhang, K.; Wu, D.; Nazir, A.; Jiang, J.; Liao, W.-H. Big data, machine learning, and digital twin assisted additive manufacturing: a review.Mater. Design2024,244, 113086..

Faruque, M. O.; Lee, Y.; Wyckoff, G. J.; Lee, C. H. Application of 4D printing and AI to cardiovascular devices.J. Drug Deliv. Sci. Technol.2023,80, 104162..

Cao, Y.; Xu, B.; Li, B.; Fu, H. Advanced design of soft robots with artificial intelligence.Nano-Micro Lett.2024,16, 214..

Rane, N.; Choudhary, S.; Rane, J. Enhanced product design and development using Artificial Intelligence (AI), Virtual Reality (VR), Augmented Reality (AR), 4D/5D/6D Printing, Internet of Things (IoT), and blockchain: a review.Virtual Reality (VR), Augmented Reality (AR) D2023,4, 4644059..

Ghazal, A. F.; Zhang, M.; Mujumdar, A. S.; Ghamry, M. Progress in 4D/5D/6D printing of foods: applications and R&D opportunities.Critical Reviews in Food Science and Nutrition2023,63, 7399−7422..

Jain, P.; Kathuria, H.; Dubey, N. Advances in 3D bioprinting of tissues/organs for regenerative medicine andin-vitromodels.Biomaterials2022,287, 121639..

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Nature-Inspired pH-Responsive Hydrogels with Rapid and High Contrast Changes in Color, Fluorescence, and Shape Simultaneously

Tough Semi-interpenetrating Polyvinylpyrrolidone/Polyacrylamide Hydrogels Enabled by Bioinspired Hydrogen-bonding Induced Phase Separation

Intestine Enzyme-responsive Polysaccharide-based Hydrogel to Open Epithelial Tight Junctions for Oral Delivery of Imatinib against Colon Cancer

Related Author

Le-Ping Xiao

Lv-Ming Qiu

Zhen Wu

Guo-Jie Wang

Qiong-Jun Xu

Zhao-Yang Yuan

Chang-Cheng Wang

Hao Liang

Related Institution

School of Materials Science and Engineering, University of Science and Technology Beijing

State Key Laboratory of Polymer Materials Engineering, College of Polymer Science and Engineering, Sichuan University

Department of Gynaecology and Obstetrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University

Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University

Department of Orthopaedic Surgery, West China Hospital, Sichuan University

⁰