10.57647/pibm.2025.17542

Development of Polylactic Acid/Hydroxyapatite Composite Filaments for 3D Printing of Bone Tissue Engineering Scaffolds

  1. Center for Nanotechnology & Biomaterials Application and Research (NBUAM), Marmara University, Istanbul, 34890, Turkey
  2. Department of Nanoscience and Nanoengineering, Nanotechnology Institute, Gebze Technical University, Turkey
  3. Department of Mechanical Engineering, Faculty of Technology, Marmara University, Turkey
  4. National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor Street, 077125 Magurele, Romania
  5. Department of Metallurgical and Materials Engineering, Faculty of Technology, Marmara University, Istanbul 34890, Turkey

Published in Issue 2025-09-29

How to Cite

Cinici, B., Gozonunde, S., Kurt, M., Duta, L., & Gunduz, O. (2025). Development of Polylactic Acid/Hydroxyapatite Composite Filaments for 3D Printing of Bone Tissue Engineering Scaffolds. Progress in Biomaterials. https://doi.org/10.57647/pibm.2025.17542

Abstract

This study addresses the development of novel composite filaments tailored for 3D printing applications in bone tissue engineering. The granules were fabricated by blending polylactic acid with commercial hydroxyapatite (HA) at different weight ratios of 10, 20, 30, and 40% (i.e., PLA/HA_10, PLA/HA_20, PLA/HA_30, and PLA/HA_40), using twin-screw extrusion. The resulting granules were subsequently processed into filaments through single-screw extrusion. The as-obtained filaments were comprehensively characterized in terms of thermal stability, morphological features, mechanical properties, and biological performance.

It should be emphasized that the variation in HA concentration played a critical role in optimizing both the mechanical and biological performance of the composite filaments. Mechanical testing demonstrated increased elastic modulus for PLA/HA_10 and PLA/HA_20 composites. However, higher HA concentrations adversely affected the tensile strength, likely due to particle agglomeration and poor interfacial adherence between the polymer matrix and ceramic phase. In vitro biological evaluation revealed that low-to-moderate HA concentrations (i.e., 10 and 20%) improved cytocompatibility and promoted cell attachment. These findings underscore the importance of carefully tailoring the HA content to develop functional composite materials suitable for bone scaffold fabrication, with promising implications for future clinical applications in bone tissue engineering.

Keywords

  • 3D printing,
  • Filament,
  • Bone tissue,
  • Hydroxyapatite‒biopolymer blending,
  • Biomedical applications,
  • Industry

References

  1. Aghaiee S, Azdast T, Hasanzadeh R, Farhangpazhouh F (2024) Fabrication of bone tissue engineering scaffolds with a hierarchical structure using combination of 3D printing/gas foaming techniques. J Appl Polym Sci 141(16): e55238. https://doi.org/10.1002/app.55238.
  2. Åkerlund E, Diez-Escudero A, Grzeszczak A, Persson C (2022) The effect of PCL addition on 3D-printable PLA/HA composite filaments for the treatment of bone defects. Polymers 14(16):3305. https://doi.org/10.3390/polym14163305.
  3. Alonzo M, Primo FA, Kumar SA, Mudloff JA, Dominguez E, Fregoso G, Ortiz N, Weiss WM, Joddar B (2021) Bone tissue engineering techniques, advances, and scaffolds for treatment of bone defects. Curr Opin Biomed Eng 17:100248. https://doi.org/10.1016/j.cobme.2020.100248.
  4. Azdast T, Hasanzadeh R (2021) Polylactide scaffold fabrication using a novel combination technique of fused deposition modeling and batch foaming: dimensional accuracy and structural properties. Int J Adv Manuf Technol 114:1309–1321. https://doi.org/10.1007/s00170-021-06915-9.
  5. Beheshtizadeh N, Azami M, Abbasi H, Farzin A (2022) Applying extrusion-based 3D printing technique accelerates fabricating complex biphasic calcium phosphate-based scaffolds for bone tissue regeneration. J Adv Res 40:69‒94. https://doi.org/10.1016/j.jare.2021.12.012.
  6. Bernardes GP, Andrade MP, Poletto M, Luiz NR, Santana RMC, Forte MMdC (2023) Evaluation of Thermal Decomposition Kinetics of Poly (Lactic Acid)/Ethylene Elastomer (EE) Blends. Polymers 15:4324. https://doi.org/10.3390/polym15214324.
  7. Bernardo MP, da Silva BCR, Hamouda AEI, et al. (2022) PLA/Hydroxyapatite scaffolds exhibit in vitro immunological inertness and promote robust osteogenic differentiation of human mesenchymal stem cells without osteogenic stimuli. Sci Rep 12:2333. https://doi.org/10.1038/s41598-022-05207-w.
  8. Bose S, Roy M, Bandyopadhyay A (2012) Recent advances in bone tissue engineering scaffolds. Trends Biotechnol 30(10):546-554. https://doi.org/10.1016/j.tibtech.2012.07.005.
  9. Chen H, Han Q, Wang C, Liu Y, Chen B, Wang J (2020) Porous scaffold design for additive manufacturing in orthopedics: a review. Front Bioeng Biotechnol 8:609. https://doi.org/10.3389/fbioe.2020.00609.
  10. Chocholata P, Kulda V, Babuska V (2019) Fabrication of scaffolds for bone-tissue regeneration. Materials 12(4):568. https://doi.org/10.3390/ma12040568.
  11. Cinici B, Yaba S, Kurt M, Yalcin HC, Duta L, Gunduz O. Fabrication Strategies for Bioceramic Scaffolds in Bone Tissue Engineering with Generative Design Applications. Biomimetics 2024 9:409. https://doi.org/10.3390/biomimetics9070409.
  12. Collins MN, Ren G, Young K, Pina S, Reis RL, Oliveira JM (2021) Scaffold fabrication technologies and structure/function properties in bone tissue engineering. Adv Funct Mater 31(21):2010609. https://doi.org/10.1002/adfm.202010609.
  13. Custodio CL, Broñola PJM, Cayabyab SR, Lagura VU, Celorico JR, Basilia BA (2021) Powder Loading Effects on the Physicochemical and Mechanical Properties of 3D Printed Poly Lactic Acid/Hydroxyapatite Biocomposites. Int J Bioprint 28;7(1):326. https://doi.org/10.18063/ijb.v7i1.326.
  14. Dal Poggetto G, D'Amora U, Ronca A, Raucci MG, Soriente A, d'Ayala GG, Laurienzo P (2025) Chemical modification of PLA for the design of 3D printed nanocomposite scaffolds with enhanced degradability for bone tissue engineering. Polym Composite 46(9):7964-7980. https://doi.org/10.1002/pc.29470.
  15. Ebrahimi F, Ramezani Dana H (2022) Polylactic acid (PLA) polymers: from properties to biomedical applications. Int J Polym Mater Po 71(15):1117‒1130. https://doi.org/10.1080/00914037.2021.1944140.
  16. Elsen SR, Mahendran T, Atkare PP, Bhosale AA (2021) Fabrication of Bio-Scaffold by Additive manufacturing technique for Bone Synthesis using Generative Design. In IOP Conference Series: Materials Science and Engineering 1123(1):012068. https://doi.org/10.1088/1757-899X/1123/1/012068.
  17. Foroughi AH, Valeri C, Razavi MJ (2024) A review of computational optimization of bone scaffold architecture: Methods, challenges, and perspectives. Prog Biom Eng 7:012003. https://doi.org/10.1088/2516-1091/ad879a.
  18. Francis A (2021) Biological evaluation of preceramic organosilicon polymers for various healthcare and biomedical engineering applications: A review. J Biomed Mater Res B: Appl Biomat 109(5): 744‒764. https://doi.org/10.1002/jbm.b.34740.
  19. Gao W, Zhang Y, Ramanujan D, Ramani K, Chen Y, Williams CB, Wang CCL, Shin Y, Zhang S, Zavattieri PD (2015) The status, challenges, and future of additive manufacturing in engineering. Comput Aided Design 69:65‒89. https://doi.org/10.1016/j.cad.2015.04.001.
  20. Ghilan A, Chiriac AP, Nita LE, Rusu AG, Neamtu I, Chiriac VM (2020) Trends in 3D printing processes for biomedical field: opportunities and challenges. J Polym Environ 28:1345‒1367. https://doi.org/10.1007/s10924-020-01722-x.
  21. Hasanzadeh R, Azdast T, Mojaver M, Darvishi MM, Park CB (2022) Cost-effective and reproducible technologies for fabrication of tissue engineered scaffolds: The state-of-the-art and future perspectives. Polymer 244:124681. https://doi.org/10.1016/j.polymer.2022.124681.
  22. Hasanzadeh R, Mihankhah P, Azdast T, Rasouli A, Shamkhali M, Park CB (2023) Biocompatible tissue-engineered scaffold polymers for 3D printing and its application for 4D printing. Chem Eng J 476:146616. https://doi.org/10.1016/j.cej.2023.146616.
  23. Ilyas RA, Zuhri MYM, Aisyah HA, Asyraf MRM, Hassan SA, Zainudin ES, Sapuan SM, Sharma S, Bangar SP, Jumaidin R, Nawab Y, Faudzi AAM, Abral H, Asrofi M, Syafri E, Sari NH (2022) Natural fiber-reinforced polylactic acid, polylactic acid blends and their composites for advanced applications. Polymers 14(1):202. https://doi.org/10.3390/polym14010202.
  24. Kaczmarek H, Nowick M, Vuković-Kwiatkowska I, Nowakowska S (2013) Crosslinked blends of poly (lactic acid) and polyacrylates: AFM, DSC and XRD studies. J Polym Res 20:1‒12. https://doi.org/10.1007/s10965-013-0091-y.
  25. Kanwar S, Vijayavenkataraman S (2021) Design of 3D printed scaffolds for bone tissue engineering: A review. Bioprinting 24:e00167. https://doi.org/10.1016/j.bprint.2021.e00167.
  26. Kumar A, Nune KC, Murr LE, Misra RDK (2016) Biocompatibility and mechanical behaviour of three-dimensional scaffolds for biomedical devices: process–structure–property paradigm. Int Mater Rev 61(1):20‒45. https://doi.org/10.1080/09506608.2015.1128310.
  27. Lyu S, Huang C, Zhang X, Li H (2019) Effect of thermal processing on the crystallization behavior of PLA/HA composites. J Appl Polym Sci 136(18):47452. https://doi.org/10.1002/app.47452.
  28. Martinez-Marquez D, Mirnajafizadeh A, Carty CP, Stewart RA (2018) Application of quality by design for 3D printed bone prostheses and scaffolds. PloS One 13(4):e0195291. https://doi.org/10.1371/journal.pone.0195291.
  29. Mathieu LM, Mueller TL, Bourban PE, Pioletti DP, Müller R, Månson JAE (2006) Architecture and properties of anisotropic polymer composite scaffolds for bone tissue engineering. Biomaterials 27(6):905‒916. https://doi.org/10.1016/j.biomaterials.2005.07.015.
  30. Murariu M, Galluzzi A, Paint Y, Murariu O, Raquez J-M, Polichetti M, Dubois P (2021) Pathways to Green Perspectives: Production and Characterization of Polylactide (PLA) Nanocomposites Filled with Superparamagnetic Magnetite Nanoparticles. Materials 14:5154. https://doi.org/10.3390/ma14185154.
  31. O'Brien FJ (2011) Biomaterials & scaffolds for tissue engineering. Mater Today 14(3):88‒95. https://doi.org/10.1016/S1369-7021(11)70058-X.
  32. Orozco-Díaz CA, Moorehead R, Reilly GC, Gilchrist F, Miller C (2020) Characterization of a composite polylactic acid-hydroxyapatite 3D-printing filament for bone-regeneration. Biomed Phys Eng Express 6(2):025007. https://doi.org/10.1088/2057-1976/ab73f8.
  33. Pandele AM, Comanici FE, Carp CA, Miculescu F, Iovu H, Voicu SI, Thakur VK (2020) Thermal and mechanical behavior of cellulose acetate–hydroxyapatite micro- and nano-composites obtained by an eco-friendly approach. Materials 13(2):274. https://doi.org/10.3390/ma13020274.
  34. Rao SH, Harini B, Shadamarshan RPK, Balagangadharan K, Selvamurugan N (2018) Natural and synthetic polymers/bioceramics/bioactive compounds-mediated cell signalling in bone tissue engineering. Int J Biol Macromol 110:88‒96. https://doi.org/10.1016/j.ijbiomac.2017.09.029.
  35. Rasouli A, Azdast T, Mohammadzadeh H et al. (2022) Morphological properties and mechanical performance of polylactic acid scaffolds fabricated by a novel fused filament fabrication/gas foaming coupled method. Int J Adv Manuf Technol 119:7463–7474. https://doi.org/10.1007/s00170-022-08743-x.
  36. Roohani-Esfahani SI, Newman P, Zreiqat H (2016) Design and fabrication of 3D printed scaffolds with a mechanical strength comparable to cortical bone to repair large bone defects. Sci Rep 6(1):19468. https://doi.org/10.1038/srep19468.
  37. Taib NAAB, Rahman MR, Huda D, Kuok KK, Hamdan S, Bakri MKB, Khan A (2023) A review on poly lactic acid (PLA) as a biodegradable polymer. Polym Bull 80(2):1179‒1213. https://doi.org/10.1007/s00289-022-04160-y.
  38. Unal S, Oktar FN, Mahirogullari M, Gunduz O (2021) Bone structure and formation: A new perspective. In Bioceramics 175-193. Elsevier. https://doi.org/10.1016/B978-0-08-102999-2.00009-0.
  39. Wang W, Zhang B, Zhao L, Li M, Han Y, Wang L, Zhang Z, Li J, Zhou C, Liu L (2021) Fabrication and properties of PLA/nano-HA composite scaffolds with balanced mechanical properties and biological functions for bone tissue engineering application. Nanotechnol Rev 10(1):1359‒1373. https://doi.org/10.1515/ntrev-2021-0083.
  40. Wijerathne HS, Yan D, Zeng B, Xie Y, Hu H, Wickramaratne MN, Han Y (2020) Effect of nano-hydroxyapatite on protein adsorption and cell adhesion of poly (lactic acid)/nano-hydroxyapatite composite microspheres. SN Appl Sci 2:1‒8. https://doi.org/10.1007/s42452-020-2531-8.
  41. Wu D, Spanou A, Diez-Escudero A, Persson C (2020) 3D-printed PLA/HA composite structures as synthetic trabecular bone: A feasibility study using fused deposition modeling. J Mech Behav Biomed 103:103608. https://doi.org/10.1016/j.jmbbm.2019.103608.
  42. Wu J, Qian X, Wang MY (2019) Advances in generative design. Comput Aided Design 116(102733):10‒1016. https://doi.org/10.1016/j.cad.2019.102733.
  43. Zhang B, Wang L, Song P, Pei X, Sun H, Wu L, Zhang X (2021) 3D printed bone tissue regenerative PLA/HA scaffolds with comprehensive performance optimizations. Mater Design 201:109490. https://doi.org/10.1016/j.matdes.2021.109490.
  44. Zhang L, Yang G, Johnson BN, Jia X (2019) Three-dimensional (3D) printed scaffold and material selection for bone repair. Acta Biomater 84:16‒33. https://doi.org/10.1016/j.actbio.2018.11.039.