Abstract
Additive manufacturing is being utilised in biomedical applications for drug delivery and soft tissue engineering as a key enabling technology for precision medicine. Unlike conventional manufacturing techniques, additive manufacturing can fabricate customised interventions with relative ease. In drug delivery, other drivers for growth in the technology is the production of complex dosage forms, incorporating multiple drugs and materials, and the pursuit of on-demand manufacturing. For tissue engineering applications, additive manufacturing is creating 3D scaffolds to aid or replace the native tissue with morphology and internal architecture which mimic the final shape and structure of the defective tissue. The chapter details the utilisation of additive manufacturing in the production of pharmaceutical dosage forms, spanning simple flat-faced oral tablets to more complex drug-delivery systems that provide for the independent release of multiple drug compounds. For tissue engineering applications, the chapter describes the production of scaffolds for various soft tissue scaffolds currently under development by research teams worldwide.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Allen, L. V., Popovich, N. G., & Ansel, H. (2015). Ansel’s pharmaceutical dosage forms and drug delivery systems. Journal of Chemical Information and Modeling. https://doi.org/10.1017/CBO9781107415324.004.
Alomari, M., et al. (2015). Personalised dosing: Printing a dose of one’s own medicine. International Journal of Pharmaceutics, 494(2), 568–577. https://doi.org/10.1016/j.ijpharm.2014.12.006.
Aulton, M. E. (2001). Pharmaceutics: The science of dosage form design. Edinburgh: Churchill Livingstone. https://doi.org/10.1017/CBO9781107415324.004.
Beck, R. C. R., et al. (2017). 3D printed tablets loaded with polymeric nanocapsules: An innovative approach to produce customized drug delivery systems. International Journal of Pharmaceutics. https://doi.org/10.1016/j.ijpharm.2017.05.074.
Blake, N. J., et al. (2016). HHS public access. Advanced Functional Materials, 25(39), 6205–6217. https://doi.org/10.1002/adfm.201501760.3D.
Boccaccini, A. R., & Maquet, V. (2003). Bioresorbable and bioactive polymer/Bioglass® composites with tailored pore structure for tissue engineering applications. Composites Science and Technology, 63, 2417–2429. https://doi.org/10.1016/S0266-3538(03)00275-6.
Bose, S., et al. (2018). Additive manufacturing of biomaterials. Progress in Materials Science, 93, 45–111. https://doi.org/10.1016/j.pmatsci.2017.08.003.
Cao, T., Ho, K.-H., & Teoh, S.-H. (2003). Scaffold design and in vitro study of osteochondral coculture in a three-dimensional porous polycaprolactone scaffold fabricated by fused deposition modeling. Tissue Engineering, 9(Suppl 1), 103–112. https://doi.org/10.1089/10763270360697012.
Cengiz, I. F., et al. (2016). Building the basis for patient-specific meniscal scaffolds: From human knee MRI to fabrication of 3D printed scaffolds. Bioprinting, 1–2, 1–10. https://doi.org/10.1016/j.bprint.2016.05.001.
Ceretti, E., et al. (2017). Multi-layered scaffolds production via fused deposition modeling (FDM) using an open source 3D printer: Process parameters optimization for dimensional accuracy and design reproducibility. Procedia CIRP, 65, 13–18. https://doi.org/10.1016/j.procir.2017.04.042.
Chai, X., et al. (2017). Fused deposition modeling (FDM) 3D printed tablets for intragastric floating delivery of domperidone. Scientific Reports, 7(1), 2829. https://doi.org/10.1038/s41598-017-03097-x.
Chen, L. J., & Wang, M. (2002). Production and evaluation of biodegradable composites based on PHB-PHV copolymer. Biomaterials, 23(13), 2631–2639. https://doi.org/10.1016/S0142-9612(01)00394-5.
Chen, G. Q., & Wu, Q. (2005). The application of polyhydroxyalkanoates as tissue engineering materials. Biomaterials, 26(33), 6565–6578. https://doi.org/10.1016/j.biomaterials.2005.04.036.
Chhaya, M. P., et al. (2015). Sustained regeneration of high-volume adipose tissue for breast reconstruction using computer aided design and biomanufacturing. Biomaterials, 52(1), 551–560. https://doi.org/10.1016/j.biomaterials.2015.01.025.
Chia, H. N., & Wu, B. M. (2015). Recent advances in 3D printing of biomaterials. Journal of Biological Engineering, 9(1), 1–14. https://doi.org/10.1186/s13036-015-0001-4.
Chiulan, I., et al. (2017). Recent advances in 3D printing of aliphatic polyesters. Bioengineering, 5(1), 2. https://doi.org/10.3390/bioengineering5010002.
Choonara, Y. E., et al. (2016). 3D-printing and the effect on medical costs: A new era? Expert Review of Pharmacoeconomics & Outcomes Research, 16(1), 23–32. https://doi.org/10.1586/14737167.2016.1138860.
Davis, S. S., et al. (2005). Formulation strategies for absorption windows. Drug Discovery Today, 10(4), 249–257.
Drummer, D., Cifuentes-Cuéllar, S., & Rietzel, D. (2012). Suitability of PLA/TCP for fused deposition modeling. Rapid Prototyping Journal, 18(6), 500–507. https://doi.org/10.1108/13552541211272045.
Eckardt, M. A., et al. (2011). Not all hemangiomas are benign—Epithelioid hemangioendothelioma: An aggressive vascular lesion in children. Pediatric Hematology and Oncology, 28, 622–624. https://doi.org/10.3109/08880018.2011.584609.
FDA. (2013). Federal food, drug, and cosmetic act. In Pharmacy law: Desk reference (pp. 1–692). Boca Raton, FL: CRC Press. https://doi.org/10.1002/9780471462422.eoct415.
Felgueiras, H. P., & Amorim, M. T. P. (2017). Functionalization of electrospun polymeric wound dressings with antimicrobial peptides. Colloids and Surfaces B: Biointerfaces, 156, 133–148. https://doi.org/10.1016/j.colsurfb.2017.05.001.
Friedrich, R. B., et al. (2010a). Drying polymeric drug-loaded nanocapsules: The wet granulation process as a promising approach. Journal of Nanoscience and Nanotechnology, 10(1), 616–621. https://doi.org/10.1166/jnn.2010.1732.
Friedrich, R. B., et al. (2010b). Tablets containing drug-loaded polymeric nanocapsules: An innovative platform. Journal of Nanoscience and Nanotechnology, 10(9), 5885–5888. https://doi.org/10.1166/jnn.2010.2464.
Fuenmayor, E., et al. (2018). Material considerations for fused-filament fabrication of solid dosage forms. Pharmaceutics, 10(2), 44. https://doi.org/10.3390/pharmaceutics10020044.
Genina, N., et al. (2016). Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices. European Journal of Pharmaceutical Sciences, 90, 53–63. https://doi.org/10.1016/j.ejps.2015.11.005.
Gioumouxouzis, C. I., et al. (2017). 3D printed oral solid dosage forms containing hydrochlorothiazide for controlled drug delivery. Journal of Drug Delivery Science and Technology, 40, 164–171. https://doi.org/10.1016/j.jddst.2017.06.008.
Gioumouxouzis, C. I., et al. (2018). A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery. European Journal of Pharmaceutical Sciences, 120(2017), 40–52. https://doi.org/10.1016/j.ejps.2018.04.020.
Goyanes, A., et al. (2014). Fused-filament 3D printing (3DP) for fabrication of tablets. International Journal of Pharmaceutics, 476(1–2), 88–92. https://doi.org/10.1016/j.ijpharm.2014.09.044.
Goyanes, A., Wang, J., et al. (2015a). 3D printing of medicines: Engineering novel oral devices with unique design and drug release characteristics. Molecular Pharmaceutics, 12(11), 4077–4084. https://doi.org/10.1021/acs.molpharmaceut.5b00510.
Goyanes, A., Robles Martinez, P., et al. (2015b). Effect of geometry on drug release from 3D printed tablets. International Journal of Pharmaceutics. https://doi.org/10.1016/j.ijpharm.2015.04.069.
Goyanes, A., Chang, H., et al. (2015c). Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing. International Journal of Pharmaceutics, 496(2), 414–420. https://doi.org/10.1016/j.ijpharm.2015.10.039.
Goyanes, A., et al. (2017). Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing. International Journal of Pharmaceutics, 527(1–2), 21–30. https://doi.org/10.1016/j.ijpharm.2017.05.021.
Hutmacher, D. W., et al. (2001a). Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. Journal of Biomedical Materials Research, 55(2), 203–216. https://doi.org/10.1002/1097-4636(200105)55:2<203::AID-JBM1007>3.0.CO;2-7.
Hutmacher, D. W., Schantz, T., Zein, I., Ng, K. W., Teoh, S. H., & Tan, K. C. (2001b). Mechanical properties and cell cultural response of polycalrolactone scaffolds designed and fabricated via fused deposition modelling. Journal of Biomedial Materials Research, 55, 203–216.
Hwang, Y. C., et al. (2013). Efficacy and safety of glimepiride/metformin sustained release once daily vs. glimepiride/metformin twice daily in patients with type 2 diabetes. International Journal of Clinical Practice, 67(3), 236–243. https://doi.org/10.1111/ijcp.12071.
Jeon, J. E., et al. (2014). Multiphasic construct studied in an ectopic osteochondral defect model. Journal of the Royal Society Interface, 11(95), 20140184–20140184. https://doi.org/10.1098/rsif.2014.0184.
Jonathan, G., & Karim, A. (2016). 3D printing in pharmaceutics: A new tool for designing customized drug delivery systems. International Journal of Pharmaceutics, 499(1–2), 376–394. https://doi.org/10.1016/j.ijpharm.2015.12.071.
Jones, D. S. (2016). FASTtrack: Pharmaceutics—Dosage form and design, antimicrobial agents and chemotherapy. Cambridge: Cambridge University Press. https://doi.org/10.1128/AAC.03728-14.
Khaled, S. A., et al. (2015). 3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles. Journal of Controlled Release, 217, 308–314. https://doi.org/10.1016/j.jconrel.2015.09.028.
Kim, J. Y., & Cho, D. W. (2009). Blended PCL/PLGA scaffold fabrication using multi-head deposition system. Microelectronic Engineering, 86(4–6), 1447–1450. https://doi.org/10.1016/j.mee.2008.11.026.
Kolan, K., et al. (2017). Solvent based 3D printing of biopolymer/bioactive glass composite and hydrogel for tissue engineering applications. Procedia CIRP, 65, 38–43. https://doi.org/10.1016/j.procir.2017.04.022.
Korpela, J., et al. (2013). Biodegradable and bioactive porous scaffold structures prepared using fused deposition modeling. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 101(4), 610–619. https://doi.org/10.1002/jbm.b.32863.
Lam, C. X., et al. (2008). Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds: Accelerated versus simulated physiological conditions. Biomedical Materials, 3(3), 34108. https://doi.org/10.1088/1748-6041/3/3/034108.
Lam, C. X. F., et al. (2009). Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo. Journal of Biomedical Materials Research Part A, 90(3), 906–919. https://doi.org/10.1002/jbm.a.32052.
Lee, M., Dunn, J. C. Y., & Wu, B. M. (2005). Scaffold fabrication by indirect three-dimensional printing. Biomaterials, 26(20), 4281–4289. https://doi.org/10.1016/j.biomaterials.2004.10.040.
Li, Q., et al. (2017). Preparation and investigation of controlled-release glipizide novel oral device with three-dimensional printing. International Journal of Pharmaceutics, 525(1), 5–11. https://doi.org/10.1016/j.ijpharm.2017.03.066.
Liang, K., et al. (2018). 3D printing of a wearable personalized oral delivery device: A first-in-human study. Science Advances, 4(5), 1–12. https://doi.org/10.1126/sciadv.aat2544.
Lim, S. H., et al. (2016). Three-dimensional printing of carbamazepine sustained-release scaffold. Journal of Pharmaceutical Sciences, 105(7), 2155–2163. https://doi.org/10.1016/j.xphs.2016.04.031.
Lim, S. H., et al. (2018). 3D printed drug delivery and testing systems—A passing fad or the future? Advanced Drug Delivery Reviews. https://doi.org/10.1016/j.addr.2018.05.006.
Mahato, R. I., & Narang, A. S. (2012). Pharmaceutical dosage forms and drug delivery (2nd ed.). Boca Raton, FL: CRC Press.
Mannoor, M. S., et al. (2013). 3D printed bionic ears. Nano Letters, 13(6), 2634–2639. https://doi.org/10.1021/nl4007744.
Mansour, G., & Tzetzis, D. (2013). Nanomechanical characterization of hybrid multiwall carbon nanotube and fumed silica epoxy nanocomposites. Polymer - Plastics Technology and Engineering, 52(10), 1054–1062. https://doi.org/10.1080/03602559.2013.769581.
Melocchi, A., et al. (2016). Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling. International Journal of Pharmaceutics, 509(1–2), 255–263. https://doi.org/10.1016/j.ijpharm.2016.05.036.
Mennella, J. A., et al. (2015). Children’s perceptions about medicines: Individual differences and taste. BMC Pediatrics, 15(1), 1–6. https://doi.org/10.1186/s12887-015-0447-z.
Mitra, A. K., Lee, C. H., & Cheng, K. (2013). Advance drug delivery. Journal of Chemical Information and Modeling. https://doi.org/10.1017/CBO9781107415324.004.
Norman, J., et al. (2017). A new chapter in pharmaceutical manufacturing: 3D-printed drug products. Advanced Drug Delivery Reviews, 108, 39–50. https://doi.org/10.1016/j.addr.2016.03.001.
Okwuosa, T. C., Stefaniak, D., et al. (2016a). A lower temperature FDM 3D printing for the manufacture of patient-specific immediate release tablets. Pharmaceutical Research, 33(11), 2704–2712. https://doi.org/10.1007/s11095-016-1995-0.
Okwuosa, T. C., Pereira, B. C., et al. (2016b). Fabricating a shell-core delayed release tablet using dual FDM 3D printing for patient-centred therapy. Pharmaceutical Research, 1, 1–11. https://doi.org/10.1007/s11095-016-2073-3.
Olszewski, R., Szymor, P., & Kozakiewicz, M. (2014). Accuracy of three-dimensional, paper-based models generated using a low-cost, three-dimensional printer. Journal of Cranio-Maxillofacial Surgery, 42(8), 1847–1852. https://doi.org/10.1016/j.jcms.2014.07.002.
Paes, A. H. P., Barker, A., & Soe-Agnie, C. J. (1997). Impact of dosage frequency on patient compliance. Diabetes Care, 20(10), 1512–1517. https://doi.org/10.2337/diacare.20.10.1512.
Park, K. (2015). 3D printing of 5-drug polypill. Journal of Controlled Release, 217, 352. https://doi.org/10.1016/j.jconrel.2015.10.014.
Pawar, V. K., et al. (2012). Industrial perspective of gastroretentive drug delivery systems: Physicochemical, biopharmaceutical, technological and regulatory consideration. Expert Opinion on Drug Delivery, 9(5), 551–565.
Pietrzak, K., Isreb, A., & Alhnan, M. A. (2015). A flexible-dose dispenser for immediate and extended release 3D printed tablets. European Journal of Pharmaceutics and Biopharmaceutics, 96, 380–387. https://doi.org/10.1016/j.ejpb.2015.07.027.
Poh, P. S. P., et al. (2016). Polylactides in additive biomanufacturing. Advanced Drug Delivery Reviews, 107, 228–246. https://doi.org/10.1016/j.addr.2016.07.006.
Pok, S., et al. (2013). A multilayered scaffold of a chitosan and gelatin hydrogel supported by a PCL core for cardiac tissue engineering. Acta Materialia, 9(3), 5630–5642. https://doi.org/10.1016/j.actbio.2012.10.032.
Poulin, E., et al. (2015). Towards real-time 3D ultrasound planning and personalized 3D printing for breast HDR brachytherapy treatment. Radiotherapy and Oncology, 114(3), 335–338. https://doi.org/10.1016/j.radonc.2015.02.007.
Rabionet, M., et al. (2018). 3D-printed tubular scaffolds for vascular tissue engineering. Procedia CIRP, 68(4), 352–357. https://doi.org/10.1016/J.PROCIR.2017.12.094.
Ravi, P., Shiakolas, P. S., & Welch, T. R. (2017). Poly-L-lactic acid: Pellets to fiber to fused filament fabricated scaffolds, and scaffold weight loss study. Additive Manufacturing, 16, 167–176. https://doi.org/10.1016/j.addma.2017.06.002.
Reddymasu, S. C., Soykan, I., & Mccallum, R. W. (2007). Domperidone: Review of pharmacology and clinical applications in gastroenterology. The American Journal of Gastroenterology, 102, 2036–2045. https://doi.org/10.1111/j.1572-0241.2007.01255.x.
Sadia, M., et al. (2016). Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets. International Journal of Pharmaceutics, 513(1–2), 659–668. https://doi.org/10.1016/j.ijpharm.2016.09.050.
Sadia, M., et al. (2018). Channelled tablets: An innovative approach to accelerating drug release from 3D printed tablets. Journal of Controlled Release, 269(9), 355–363. https://doi.org/10.1016/j.jconrel.2017.11.022.
Scaffaro, R., Lopresti, F., Botta, L., Rigogliuso, S., & Ghersi, G. (2016).Preparation of three-layered porous PLA/PEG scaffold: relationship between morphology, mechanical behavior and cell permeability. Journal of the Mechanical Behavior of Biomedical Materials, 54, 8–20. https://doi.org/10.1016/j.jmbbm.2015.08.033
Scott, S., et al. (2018). Polymeric 3D printed structures for soft-tissue engineering. Journal of Applied Polymer Science, 135(24), 46279. https://doi.org/10.1002/app.46279.
Scoutaris, N., Ross, S. A., & Douroumis, D. (2018). 3D printed “Starmix” drug loaded dosage forms for paediatric applications. Pharmaceutical Research, 35(2), 1–11. https://doi.org/10.1007/s11095-017-2284-2.
Seyednejad, H., et al. (2012). In vivo biocompatibility and biodegradation of 3D-printed porous scaffolds based on a hydroxyl-functionalized poly(ε-caprolactone). Biomaterials, 33(17), 4309–4318. https://doi.org/10.1016/j.biomaterials.2012.03.002.
Shanler, M., & Basiliere, P. (2017). Hype cycle for 3D printing. Stamford, CT: Gartner Inc..
Shor, L., et al. (2009). Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering. Biofabrication, 1(1), 015003. https://doi.org/10.1088/1758-5082/1/1/015003.
Singh, S., Ramakrishna, S., & Singh, R. (2017). Material issues in additive manufacturing: A review. Journal of Manufacturing Processes, 25, 185–200. https://doi.org/10.1016/j.jmapro.2016.11.006.
Skowyra, J., Pietrzak, K., & Alhnan, M. A. (2015). Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. European Journal of Pharmaceutical Sciences, 68, 11–17. https://doi.org/10.1016/j.ejps.2014.11.009.
Strickley, R. G., et al. (2008). Pediatric drugs—A review of commercially available oral formulations. Journal of Pharmaceutical Sciences, 97(5), 1731–1774. https://doi.org/10.1002/jps.21101.
Tzetzis, D., et al. (2013). Nanoindentation measurements of fumed silica epoxy reinforced nanocomposites. Journal of Reinforced Plastics and Composites, 32(3), 163–173. https://doi.org/10.1177/0731684412463978.
Wang, F., Shor, L., Darling, A., Khalil, S., Sun, W., Güçeri, S., & Lau, A. (2004). Precision extruding deposition and characterization of cellular poly-ϵ-caprolactone tissue scaffolds. Rapid Prototyping Journal, 10(1), 42–49. https://doi.org/10.1108/13552540410512525
Wilson, C. G., & Crowley, P. J. (2011). Controlled release in oral drug delivery. Boston, MA: Springer. https://doi.org/10.1007/978-1-4614-1004-1.
Woodruff, M. A., & Hutmacher, D. W. (2010). The return of a forgotten polymer—Polycaprolactone in the 21st century. Progress in Polymer Science, 35(10), 1217–1256. https://doi.org/10.1016/j.progpolymsci.2010.04.002.
Ye, H., et al. (2018). Polyester elastomers for soft tissue engineering. Chemical Society Reviews, 47(12), 4545–4580. https://doi.org/10.1039/c8cs00161h.
Yeong, W. Y., et al. (2004). Rapid prototyping in tissue engineering: Challenges and potential. Trends in Biotechnology, 22(12), 643–652. https://doi.org/10.1016/j.tibtech.2004.10.004.
Yen, H. J., Tseng, C. S., Hsu, S. H., & Tsai, C. L. (2009). Evaluation of chondrocyte growth in the highly porous scaffolds made by fused deposition manufacturing (FDM) filled with type II collagen. Biomedical microdevices, 11(3), 615–624. https://doi.org/10.1007/s10544-008-9271-7
Yin, H. S., et al. (2010). Parents’ medication administration errors. Archives of Pediatrics & Adolescent Medicine, 164(2), 181–186. https://doi.org/10.1001/archpediatrics.2009.269.
Zein, I., et al. (2002). Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials, 23(4), 1169–1185. https://doi.org/10.1016/S0142-9612(01)00232-0.
Zhu, W., et al. (2016). 3D printing of functional biomaterials for tissue engineering. Current Opinion in Biotechnology, 40, 103–112. https://doi.org/10.1016/j.copbio.2016.03.014.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Fuenmayor, E.A., Healy, A.V., Dalton, M., Major, I. (2019). Customised Interventions Utilising Additive Manufacturing. In: Devine, D. (eds) Polymer-Based Additive Manufacturing. Springer, Cham. https://doi.org/10.1007/978-3-030-24532-0_7
Download citation
DOI: https://doi.org/10.1007/978-3-030-24532-0_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-24531-3
Online ISBN: 978-3-030-24532-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)