Advanced Medical Additive Manufacturing: From 3D to 6D Printing, Bioprinting, and Biofabrication – Applications in Pharmaceuticals and Healthcare

Phalguni Deswal¹, Anupama Deswal², Surinder Deswal³

¹ Editor, Drug and Device World, Kurukshetra, India.

² Dental Consultant, Kurukshetra, India.

³ Professor, National Institute of Technology Kurukshetra, India. 

Abstract

Advanced medical additive manufacturing, encompassing three-dimensional (3D) to six-dimensional (6D) printing technologies, bioprinting, and biofabrication, is transforming pharmaceuticals and healthcare by enabling the creation of patient-specific solutions with unprecedented precision and functionality. This review comprehensively examines the characteristics, applications, and potential of these technologies across medical domains. Three-dimensional printing facilitates customized prosthetics, implants, anatomical models for surgical planning, and personalized drug delivery systems. Four-dimensional printing introduces time-responsive smart materials that dynamically adapt to external stimuli such as heat, moisture, or magnetic fields, offering revolutionary potential for self-assembling implants and adaptive drug release systems. Five-dimensional printing incorporates additional rotational axes, enhancing the strength, precision, and material efficiency of complex structures. Six-dimensional printing integrates concepts from both 4D and 5D approaches with smart materials to create objects capable of transforming structure and functionality over time. The review details bioprinting approaches—biomimicry, autonomous self-assembly, and microtissues—alongside various printing technologies, including extrusion-based methods, inkjet printing, stereolithography, and selective laser melting. Significant applications are explored in tissue engineering for bone, joints, skin, blood vessels, and organoids; customized prosthetics and implants for orthopaedic, maxillofacial, and dental applications; and pharmaceutical applications including personalized medications with tailored drug release profiles. While transformative potential is evident, challenges persist regarding cell viability, vascularization, regulatory frameworks, material biocompatibility, and clinical translation. Future developments integrating artificial intelligence, machine learning, and point-of-care manufacturing promise to further revolutionize personalized medicine, surgical planning, and regenerative therapeutics.     

Keywords: Bioprinting, Additive manufacturing, Extrusion-based methods, Inkjet printing, Stereolithography, Selective laser melting, Personalized medicine, Tissue engineering, Drug delivery systems, Medical implants

References

1. Alqutaibi, A.Y., Alghauli, M.A., Aljohani, M.H.A., et al. (2024) ‘Advanced additive manufacturing in implant dentistry: 3D printing technologies, printable materials, current applications and future requirements’, Bioprinting, 42, e00356. https://doi.org/10.1016/j.bprint.2024.e00356  
2. Amaya-Rivas, J.L., Perero, B.S., Helguero, C.G., et al. (2024) ‘Future trends of additive manufacturing in medical applications: An overview’, Heliyon, 10(5), e26641. https://doi.org/10.1016/j.heliyon.2024.e26641
3. AN (2017) Korean researchers develop 3D-printed stem cell patch for heart patients. Arirang News. https://www.youtube.com/watch?v=reWgFTAfKTg
4. Baltazar, T., Merola, J., Catarino, C., et al. (2020) ‘Three dimensional bioprinting of a vascularized and perfusable skin graft using human keratinocytes, fibroblasts, pericytes, and endothelial cells’,  Tissue Engineering Part A: Research Advances, 26(5-6), pp. 227-238. https://doi.org/10.1089/ten.tea.2019.0201  
5. Belvedere, C., Siegler, S., Fortunato, A., et al. (2018) ‘New comprehensive procedure for custom-made total ankle replacements: Medical imaging, joint modeling, prosthesis design, and 3D printing’, Journal of Orthopaedic Research, 37(3), pp. 760-768. https://doi.org/10.1002/jor.24198  
6. Brownell, L. (2024) 3D-printed blood vessels bring artificial organs closer to reality. Wyss Institute. https://wyss.harvard.edu/news/3d-printed-blood-vessels-bring-artificial-organs-closer-to-reality/  
7. Brydone, A.S., Meek, D. and Maclaine, S. (2010) ‘Bone grafting, orthopaedic biomaterials, and the clinical need for bone engineering’, Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 224(12), pp. 1329-1343.  https://doi.org/10.1243/09544119JEIM770  
8. CC (2013) Bioengineers, physicians 3-D print ears that look, act real. Cornell Chronicle, Cornell University. https://news.cornell.edu/stories/2013/02/bioengineers-physicians-3-d-print-ears-look-act-real   
9. Dargude, S, Shinde, S., Jagdale, S., Polshettiwar, S. and Rajput, A. (2025) ‘Exploring the evolution of 5D and 6D printing: current progress, challenges, technological innovations, and transformative biomedical applications’, Hybrid Advances, 10, 100470. https://doi.org/10.1016/j.hybadv.2025.100470
10. Dekker, T.J., Steele, J.R., Federer, A.E., et al. (2018) ‘Use of patient-specific 3D-printed titanium implants for complex foot and ankle limb salvage, deformity correction, and arthrodesis procedures’, Foot Ankle Int., 39(8), pp. 916-921. https://pubmed.ncbi.nlm.nih.gov/29648876/  
11. Deswal, A. (2025) ‘Applications of 3D printing in dentistry: Present and future perspectives’, International Journal of Technology, Health and Sustainability, 1(1), pp. 31-36. https://ijths.com/wp-content/uploads/2025/12/IJTHS-010118.pdf
12. Dong, C., Petrovic, M. and Davies, I.J. (2024) ‘Applications of 3D printing in medicine: a review’, Annals of 3D Printed Medicine, 14, 100149. https://doi.org/10.1016/j.stlm.2024.100149
13. Fleischman, T. (2017) Patented biomedical implant could improve heart patient outcome. Cornell Chronicle. https://news.cornell.edu/stories/2017/08/patented-biomedical-implant-could-improve-heart-patient-outcome
14. Forrmlabs (2025) Introduction to medical 3D printing and 3D printers for healthcare. Formlabs. https://formlabs.com/blog/3d-printing-in-medicine-healthcare/?srsltid=AfmBOooPPB2vetYeAwidaxZmYOKg6LdEaifm26KKVDjKOUa2Ov_e0JnN   
15. Gambini, A. (2021) In-vision co-develops 3D printed microneedles for diabetes monitoring. VM FocusMedical AM.  https://www.voxelmatters.com/3d-printed-microneedles-for-continuous-glucose-monitoring/   
16. Godec, M., Kocijan, A., Dolinar, D., et al. (2010) ‘An investigation of the aseptic loosening of an AISI 316L stainless steel hip prosthesis’, Biomedical Materials, 5(4), 045012.  https://iopscience.iop.org/article/10.1088/1748-6041/5/4/045012   
17. Golder, J. (2022) Experts grow new 3D-printed nose on woman’s arm after she lost hers to cancer. ANANOVA.  https://ananova.news/experts-grow-new-3d-printed-nose-on-womans-arm-after-she-lost-hers-to-cancer/  
18. Jenkinson, C.G., Wood, T.L. and Chuen, J. (2025) ‘Three-Dimensional Printing in Cardiothoracic Surgery: Workflow and Clinical Applications’, Cureus., 17(6), e85530. https://doi.org/10.7759/cureus.85530
19. Jiang, Y., Jiang, H., Yang, Z., et al. (2024) ‘The current application of 3D printing simulator in surgical training’, Front. Med. (Lausanne), 11, 1443024. https://doi.org/10.3389/fmed.2024.1443024
20. Kantaros, A., Petrescu, F., Abdoli, H., et al. (2024) ‘Additive manufacturing for surgical planning and education: A review’,  Applied Sciences, 14(6), 2550. https://doi.org/10.3390/app14062550
21. Kanumilli, S.L.D., Kosuru, B.P., Shaukat, F., et al. (2024) ‘Advancements and applications of three-dimensional printing technology in surgery’, J. Med. Phys., 49(3), pp. 319-325. https://doi.org/10.4103/jmp.jmp_89_24
22. Keane, P. (2023) First 3D printed pediatric medicine trials to begin in Europe. 3D Printing.com. https://3dprinting.com/news/first-3d-printed-pediatric-medicine-trials-to-begin-in-europe/
23. Khaled, S.A., Burley, J.C., Alexander, M.R., et al. (2015a) ‘3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles’, J. Control Release, 217, pp. 308-314. https://pubmed.ncbi.nlm.nih.gov/26390808/
24. Khaled, S.A., Burley, J.C., Alexander, M.R., et al. (2015b) ‘3D printing of tablets containing multiple drugs with defined release profiles’, Int. J. Pharm., 494(2), pp. 643-650. https://pubmed.ncbi.nlm.nih.gov/26235921/ 
25. Lei, J., Tee, L.B.G., Ragunath, K, et al. (2025) ‘Three-dimensional-printed gastrointestinal tract models for surgical planning and medical education: A systematic review’, Appl. Sci., 15(13), 7384. https://doi.org/10.3390/app15137384
26. Mannan, A. and Smith, T.O. (2016) ‘Favourable rotational alignment outcomes in PSI knee arthroplasty: a Level 1 systematic review and meta-analysis’, Knee, 23(2), pp. 186-190. https://pubmed.ncbi.nlm.nih.gov/26782300/   
27. Maroni, A., Melocchi, A., Parietti, F., et al. (2017) ‘3D printed multi-compartment capsular devices for two-pulse oral drug delivery’, Journal of Controlled Release, 268, pp. 10-18. https://www.sciencedirect.com/science/article/abs/pii/S0168365917308957
28. Matijašić, G., Gretić, M., Vinčić, J., et al. (2019) ‘Design and 3D printing of multi-compartmental PVA capsules for drug delivery’, Journal of Drug Delivery Science and Technology, 52, pp. 677-686. https://doi.org/10.1016/j.jddst.2019.05.037
29. Mesko, B. (2025) 3D printing in medicine: in recent years 3D printing in medicine took a massive leap. Check out our analysis of where this exciting field stands today!. The Medical Futurist.  https://medicalfuturist.com/3d-printing-in-medicine-and-healthcare/   
30. Mohammed, A.A., Algahtani, M.S., Ahmad, M.Z., et al. (2021) ‘3D printing in medicine: technology overview and drug delivery applications’, Annals of 3D Printed Medicine, 4, 100037. https://www.sciencedirect.com/science/article/pii/S2666964121000321
31. Morrison, R.J., Hollister, S.J., Niedner, M.F., et al. (2015) ‘Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients’, Science Translational Medicine, 7(285), pp. 285ra64. https://www.science.org/doi/abs/10.1126/scitranslmed.3010825
32. Mouser, V.H.M., Levato, R., Bonassar, L.J., et al. (2016) ‘Three-dimensional bioprinting and its potential in the field of articular cartilage regeneration’, Cartilage, 8(4), pp. 327-340. https://doi.org/10.1177/1947603516665445  
33. Narra, S.P., Mittwede, P.N., Wolf, S.D., et al. (2019) ‘Additive manufacturing in total joint arthroplasty’, Orthop Clin North Am., 50(1), pp. 13–20.   https://pmc.ncbi.nlm.nih.gov/articles/PMC6555404/  
34. Organova (2025) Pioneering 3D human tissues for drug discovery. Organova. https://organovo.com/  
35. Parramon-Teixido, C.J., Rodríguez-Pombo, L., Basit, A.W., et al. (2025) ‘A framework for conducting clinical trials involving 3D printing of medicines at the point-of-care’, Drug Delivery and Translational Research, 15, pp. 3078-3097. https://link.springer.com/article/10.1007/s13346-025-01868-y
36. Qian, Z., Wang, K., Liu, S., et al. (2017) ‘Quantitative prediction of paravalvular leak in transcatheter aortic valve replacement based on tissue-mimicking 3D printing’, JACC: Cardiovascular Imaging, 10(7), pp. 719-731. https://doi.org/10.1016/j.jcmg.2017.04.005
37. RMF (2023) New wound healing research by Wake Forest Institute for Regenerative Medicine produces full thickness human bioprinted skin. Regenerative Medicine Foundation. https://regmedfoundation.org/2023/10/26/new-wound-healing-research-by-wake-forest-institute-for-regenerative-medicine-produces-full-thickness-human-bioprinted-skin/  
38. Stirrat, T., Martin, R., Baek, G., et al. (2024) ‘Pixels to precision: Neuroradiology’s leap into 3D printing for personalized medicine’, J. Clin. Imaging Sci., 14, 49. https://doi.org/10.25259/JCIS_119_2024
39. Tarista, I.C., Lee, D., Foppiani, J., et al. (2024) ‘Three-dimensional printing in surgical education: An updated systematic review of the literature’, J. Surg. Res., 300, pp. 425-431. https://doi.org/10.1016/j.jss.2024.04.077
40. TAU (2019) TAU scientists print first ever 3D heart using patient’s own cells. Tel Aviv University, Israel. https://english.tau.ac.il/news/printed_heart
41. UAFMD (2021) 3D ‘bioprinting’ used to create nose cartilage. University of Alberta Faculty of Medicine & Dentistry. https://www.sciencedaily.com/releases/2021/05/210504161704.htm   
42. Vasiliadis, A.V., Koukoulias, N. and Katakalos, K. (2022) ‘From three-dimensional (3D)- to 6D-printing technology in orthopedics: Science fiction or scientific reality?,’ J. Funct. Biomater., 13(3), 101. https://doi.org/10.3390/jfb13030101
43. Weng, T., Zhang, W., Xia, Y., et al. (2021) ‘3D bioprinting for skin tissue engineering: Current status and perspectives’, J. Tissue Eng., 12, 20417314211028574. https://doi.org/10.1177/20417314211028574
44. Wu, Y., Liu, J., Kang, L., et al. (2023) ‘An overview of 3D printed metal implants in orthopedic applications: Present and future perspectives’, Heliyon, 9(7), e17718. https://doi.org/10.1016/j.heliyon.2023.e17718   
45. Xu, G., Gao, L., Tao, K., et al. (2017) ‘Three-dimensional-printed upper limb prosthesis for a child with traumatic amputation of right wrist: A case report’, Medicine (Baltimore), 96(52), e9426.  https://pubmed.ncbi.nlm.nih.gov/29384921/