journal article·2026-04-20Open access

4D Printing in Biomedical Implants and Functional Healthcare Devices

Muhammad Shafiq, Liaqat Zeb

Abstract

Four-dimensional (4D) printing integrates additive manufacturing with stimuli-responsive materials to fabricate biomedical implants and functional healthcare devices that undergo programmed, time-dependent changes in shape or function. Unlike static 3D-printed constructs, 4D-printed systems can respond to clinically relevant stimuli such as temperature, hydration, pH, light (including near-infrared), magnetic fields, or electrical inputs. These triggers drive defined actuation mechanisms, most commonly thermomechanical shape-memory recovery, swelling-induced morphing, and magnetothermal activation. This review synthesizes the principal material platforms used for biomedical 4D printing, including shape-memory polymers and alloys, hydrogels, liquid-crystal elastomers, and responsive composites, and links material choice to device behavior and translational feasibility. Applications are discussed across self-expanding stents, cardiac occluders, tissue-engineered constructs, implantable drug delivery systems, and adaptive wearables. Key translational challenges include sterilization compatibility, manufacturing reproducibility and quality control, safe stimulus delivery, predictable biodegradation and long-term biocompatibility, and regulatory pathway definition.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Advanced Materials and Mechanics · 3D Printing in Biomedical Research · Hydrogels: synthesis, properties, applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

School of Medical Sciences, Shandong Xiehe University, Jinan 250109, China

Laboratory of Bioresources and Pharmaceutical Chemistry, Department of Chemistry, University of Bergen, 5007 Bergen, Norway

References (100+)

Show source-provided references
1. Hussain, C.G., Qadeer, M., Keçili, R., and Hussain, C.M. (2024). Computer-aided modeling principles for anatomic design. Medical Additive Manufacturing, Elsevier.10.1016/B978-0-323-95383-2.00002-0 ↗
2. Recent advances in additive manufacturing of patient-specific devices for dental and maxillofacial rehabilitation10.1016/j.dental.2024.02.006 ↗
3. 4D Printing: A Comprehensive Review of Technologies, Materials, Stimuli, Design, and Emerging Applications10.1021/acs.chemrev.4c00070 ↗
4. Recent advances in 3D bioprinted polysaccharide hydrogels for biomedical applications: A comprehensive review10.1016/j.carbpol.2024.122845 ↗
5. Recent advances in 3D printing of tough hydrogels: A review10.1016/j.compositesb.2022.109895 ↗
6. Magneto-/electro-responsive polymers toward manufacturing, characterization, and biomedical/soft robotic applications10.1016/j.apmt.2021.101306 ↗
7. Capillary-force-driven self-assembly of 4d-printed microstructures10.1002/adma.202100332 ↗
8. 4D printing: From emergence to innovation over 3D printing10.1016/j.eurpolymj.2023.112356 ↗
9. 4D printing: Historical evolution, computational insights and emerging applications10.1016/j.mseb.2023.116567 ↗
10. 4D printing of multiple shape memory polymer and nanocomposites with biocompatible, programmable and selectively actuated properties
11. Biocompatible composite hydrogel with on-demand swelling-shrinking properties for 4D bioprinting10.1039/D5BM00551E ↗
12. Exploring materials, technologies, applications, and future outlooks in 4D printing: A comprehensive survey10.1007/s40964-025-01034-3 ↗
13. Advancements and applications of 4D bioprinting in biomedical science10.1007/s10118-025-3259-0 ↗
14. Recent progress in 4D printing of stimuli-responsive polymeric materials10.1007/s11431-019-1443-1 ↗
15. Recent advances in 4D printing of advanced materials and structures for functional applications10.1002/adma.202312263 ↗
16. Digital light 4D printing of bioresorbable shape memory elastomers for personalized biomedical implantation10.1016/j.actbio.2024.02.009 ↗
17. 4D printing for biomedical applications10.1002/adma.202402301 ↗
18. Recent Advances of Photothermal Materials for Biomedical Applications10.1021/acsomega.5c03418 ↗
19. Shie, M.-Y., Shen, Y.-F., Astuti, S.D., Lee, A.K.-X., Lin, S.-H., Dwijaksara, N.L.B., and Chen, Y.-W. (2019). Review of polymeric materials in 4D printing biomedical applications. Polymers, 11.10.3390/polym11111864 ↗
20. Research progress of shape memory polymer and 4D printing in biomedical application10.1002/adhm.202201975 ↗
21. Parida, S. (2025). Fundamental Concepts, Classification, and Materials Used for 3D, 4D, and 5D Printing. Polymer Nanocomposites for 3D, 4D and 5D Printing: Fundamental to Applications, Springer.10.1007/978-981-96-4214-4_2 ↗
22. 4D-printed dynamic materials in biomedical applications: Chemistry, challenges, and their future perspectives in the clinical sector10.1021/acs.jmedchem.9b02115 ↗
23. Metallic gels for conductive 3D and 4D printing10.1016/j.matt.2023.06.015 ↗
24. Mayakrishnan, V., and Murugan, P.A. (2024). Degradation studies of resorbable materials for biomedical applications. Nanomanufacturing Techniques in Sustainable Healthcare Applications, CRC Press.10.1201/9781003470311-13 ↗
25. 4D printing of polyvinyl chloride (PVC): A detailed analysis of microstructure, programming, and shape memory performance10.1002/mame.202200677 ↗
26. Recent advances in 4D-Printed shape memory actuators10.1002/marc.202401141 ↗
27. 4D printed shape memory polymers and their structures for biomedical applications10.1007/s11431-019-1494-0 ↗
28. Zeng, C., Liu, L., Zhao, W., Xin, X., Liu, Y., and Leng, J. (Adv. Eng. Mater., 2025). Advances in Shape-Memory Polymers and Composites for Biomedical Device Applications, Adv. Eng. Mater., early view.10.1002/adem.202402145 ↗
29. Heating/solvent responsive shape-memory polymers for implant biomedical devices in minimally invasive surgery: Current status and challenge10.1002/mabi.202000108 ↗
30. Dallaev, R. (2025). Smart and biodegradable polymers in tissue engineering and interventional devices: A brief review. Polymers, 17.10.3390/polym17141976 ↗
31. Biodegradable medical implants: Reshaping future medical practice10.1002/advs.202508014 ↗
32. Lee, J., and Kang, S.-K. (2021). Principles for controlling the shape recovery and degradation behavior of biodegradable shape-memory polymers in biomedical applications. Micromachines, 12.10.3390/mi12070757 ↗
33. Machining of NiTi-shape memory alloys—A review10.1080/10910344.2017.1365894 ↗
34. Flexible and tough superelastic Co–Cr alloys for biomedical applications10.1002/adma.202202305 ↗
35. Highly bidirectional bendable actuator engineered by LCST–UCST bilayer hydrogel with enhanced interface10.1021/acsami.0c17085 ↗
36. Design and Application of Stimuli-Responsive Nanocomposite Hydrogels: A Review10.1002/marc.202401095 ↗
37. 4D bioprinting: The next-generation technology for biofabrication enabled by stimuli-responsive materials10.1088/1758-5090/9/1/012001 ↗
38. Cao, D., He, D., Zhao, Y., Jin, D., Zhang, J., and Wang, W. (2026). Ionogel Actuators: A Review. SmartBot, early view.10.1002/smb2.70026 ↗
39. 4D bioprinting: Technological advances in biofabrication10.1002/mabi.201800441 ↗
40. Liquid crystal elastomers for soft actuators
41. Hussain, M., Jull, E.I., Mandle, R.J., Raistrick, T., Hine, P.J., and Gleeson, H.F. (2021). Liquid crystal elastomers for biological applications. Nanomaterials, 11.10.3390/nano11030813 ↗
42. Magnetically-activated lipid nanocarriers in biomedical applications: A review of current status and perspective10.1002/wnan.1863 ↗
43. Recent advances, status, and opportunities of magneto-electric nanocarriers for biomedical applications10.1016/j.mam.2021.101046 ↗
44. Recent advances in ionic liquid-based hybrid materials for electroactive soft actuator applications10.1002/mame.202400279 ↗
45. Ionic liquid–polymer composites: A new platform for multifunctional applications10.1002/adfm.201909736 ↗
46. Sekar, M.P., Budharaju, H., Zennifer, A., Sethuraman, S., and Sundaramurthi, D. (2023). Four-dimension printing in healthcare. 3D Printing in Medicine, Elsevier.10.1016/B978-0-323-89831-7.00010-9 ↗
47. 4D printing of shape memory polymers, blends, and composites and their advanced applications: A comprehensive literature review10.1002/adem.202200650 ↗
48. Razzaq, M.Y., Gonzalez-Gutierrez, J., Mertz, G., Ruch, D., Schmidt, D.F., and Westermann, S. (2022). 4D printing of multicomponent shape-memory polymer formulations. Appl. Sci., 12.10.3390/app12157880 ↗
49. Exploring the potential of 3D and 4D printing in advancing stent manufacturing for cardiovascular diseases10.1016/j.eurpolymj.2024.113035 ↗
50. van Beelen, S., Smesseim, I., Guibert, N., Wijma, I., and Burgers, S. (2023). Broadening the scope for three-dimensional printed airway stents. ERJ Open Res., 9.10.1183/23120541.00673-2022 ↗
51. Kantaros, A., Petrescu, F.I.T., and Ganetsos, T. (2025). From stents to smart implants employing biomimetic materials: The impact of 4D printing on modern healthcare. Biomimetics, 10.10.3390/biomimetics10020125 ↗
52. 4D printing of customizable and reconfigurable mechanical metamaterials10.1016/j.ijmecsci.2024.109112 ↗
53. Origami derived self-assembly stents fabricated via 4D printing10.1016/j.compstruct.2022.115669 ↗
54. Direct 3D printing of thin-walled cardiovascular stents with negative poisson’s ratio (NPR) structure and functional metallic coating10.1016/j.compstruct.2022.116572 ↗
55. 4D printing of shape memory vascular stent based on βCD-g-Polycaprolactone10.1002/marc.202100176 ↗
56. 4D printing of personalized shape memory polymer vascular stents with negative Poisson’s ratio structure: A preliminary study10.1007/s11431-019-1468-2 ↗
57. Clinical grade manufacture of 3D printed patient specific biodegradable devices for pediatric airway support10.1016/j.biomaterials.2022.121702 ↗
58. Digital light 3D printing of customized bioresorbable airway stents with elastomeric properties10.1126/sciadv.abe9499 ↗
59. Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients10.1126/scitranslmed.3010825 ↗
60. 4D printing of tracheal scaffold using shape-memory polymer composite10.1016/j.matlet.2022.133238 ↗
61. Design of 4D printed shape-changing tracheal stent and remote controlling actuation10.1080/19475411.2021.1974972 ↗
62. 4D printed orbital stent for the treatment of enophthalmic invagination10.1016/j.biomaterials.2022.121886 ↗
63. Mass-producible near-body temperature-triggered 4D printed shape memory biocomposites and their application in biomimetic intestinal stents10.1016/j.compositesb.2023.110623 ↗
64. Medical application of biomimetic 4D printing10.1080/03639045.2020.1862179 ↗
65. 4D-printed biodegradable and remotely controllable shape memory occlusion devices10.1002/adfm.201906569 ↗
66. 4D printing of bioinspired absorbable left atrial appendage occluders: A proof-of-concept study10.1021/acsami.0c17192 ↗
67. Is 4D Printing at the Forefront of Transformations in Tissue Engineering and Beyond?10.1007/s44174-024-00161-9 ↗
68. Programmable tissue folding patterns in structured hydrogels10.1002/adma.202300017 ↗
69. Rosellini, E., Giordano, C., Guidi, L., and Cascone, M.G. (2024). Biomimetic approaches in scaffold-based blood vessel tissue engineering. Biomimetics, 9.10.3390/biomimetics9070377 ↗
70. Jouda, H., Larrea Murillo, L., and Wang, T. (2022). Current progress in vascular engineering and its clinical applications. Cells, 11.10.3390/cells11030493 ↗
71. 4D biofabrication using shape-morphing hydrogels10.1002/adma.201703443 ↗
72. Approach to management of nerve gaps in peripheral nerve injuries10.1016/j.injury.2022.01.031 ↗
73. Three-dimensional engineered peripheral nerve: Toward a new era of patient-specific nerve repair solutions10.1089/ten.teb.2020.0355 ↗
74. Stereolithographic 4D bioprinting of multiresponsive architectures for neural engineering10.1002/adbi.201800101 ↗
75. 4D Printed Programmable Shape-Morphing Hydrogels as Intraoperative Self-Folding Nerve Conduits for Sutureless Neurorrhaphy10.1002/adhm.202300701 ↗
76. Skeletal muscle: A review of molecular structure and function, in health and disease10.1002/wsbm.1462 ↗
77. A skeleton muscle model using GelMA-based cell-aligned bioink processed with an electric-field assisted 3D/4D bioprinting10.7150/thno.50794 ↗
78. Sharma, V., Dash, S.K., Govarthanan, K., Gahtori, R., Negi, N., Barani, M., Tomar, R., Chakraborty, S., Mathapati, S., and Bishi, D.K. (2021). Recent advances in cardiac tissue engineering for the management of myocardium infarction. Cells, 10.10.3390/cells10102538 ↗
79. 4D printed cardiac construct with aligned myofibers and adjustable curvature for myocardial regeneration10.1021/acsami.0c17610 ↗
80. Biomaterial-based 3D bioprinting strategy for orthopedic tissue engineering10.1016/j.actbio.2022.08.004 ↗
81. 4D printing of multi-responsive membrane for accelerated in vivo bone healing via remote regulation of stem cell fate10.1002/adfm.202103920 ↗
82. Advanced reconfigurable scaffolds fabricated by 4D printing for treating critical-size bone defects of irregular shapes10.1088/1758-5090/abab5b ↗
83. In-vitro and in-vivo studies of 4D printed shape memory scaffolds with bioactive fillers and coating for enhanced bone tissue regeneration10.1088/1361-665X/ac884a ↗
84. Biomaterial-based scaffolds in promotion of cartilage regeneration: Recent advances and emerging applications
85. 4D cell-condensate bioprinting10.1002/smll.202202196 ↗
86. Jammed micro-flake hydrogel for four-dimensional living cell bioprinting10.1002/adma.202109394 ↗
87. Exploring the role of mesoporous silica nanoparticle in the development of novel drug delivery systems10.1007/s13346-021-00935-4 ↗
88. Towards 4D printing in pharmaceutics
89. Utilizing 4D printing to design smart gastroretentive, esophageal, and intravesical drug delivery systems10.1002/adhm.202202631 ↗
90. Three-dimensional printing of shape memory hydrogels with internal structure for drug delivery10.1016/j.msec.2017.11.025 ↗
91. Expandable drug delivery system for gastric retention based on shape memory polymers: Development via 4D printing and extrusion10.1016/j.ijpharm.2019.118700 ↗
92. 4D printing of core–shell hydrogel capsules for smart controlled drug release10.1007/s42242-021-00175-y ↗
93. A bioinspired 4D printed hydrogel capsule for smart controlled drug release10.1016/j.mtchem.2022.100789 ↗
94. Application of artificial intelligence in wearable devices: Opportunities and challenges10.1016/j.cmpb.2021.106541 ↗
95. A review of 4D printing: Materials, structures, and designs towards the printing of biomedical wearable devices10.1016/j.bprint.2022.e00217 ↗
96. Pourfarzaneh, A., Taghavi, M., Helps, T., and Rossiter, J. (2019). Towards adaptive prosthetic sockets using 3D-printed variable-stiffness shape-memory structures. 2019 2nd IEEE International Conference on Soft Robotics (RoboSoft), IEEE.10.1109/ROBOSOFT.2019.8722811 ↗
97. 4D printing elastic composites for strain-tailored multistable shape morphing10.1021/acsami.0c17618 ↗
98. Bio-inspired motion mechanisms: Computational design and material programming of self-adjusting 4D-printed wearable systems10.1002/advs.202100411 ↗
99. Dynamic photomask-assisted direct ink writing multimaterial for multilevel triboelectric nanogenerator10.1002/adfm.201903568 ↗
100. 4D-printed self-recovered triboelectric nanogenerator for energy harvesting and self-powered sensor10.1016/j.nanoen.2021.105873 ↗