Chapter 8. 3D Printed HA Ceramic and its Composite Scaffolds for Tissue Engineering
Qing Zhou and Rujie He
1Institute of Advanced Structure Technology, Beijing Institute of Technology,
Part of the book: What to Know about Hydroxyapatite
Hydroxyapatite (HA) ceramic has gained tremendous attention in tissue engineering owing to its excellent mechanical properties, biocompatibility, and osteoconductivity. In most tissue engineering cases, complex-shaped HA scaffolds are usually needed, which brings great challenges to their manufacturing. Recently, additive manufacturing, also known as 3D printing, has been widely studied for its fabrication ability of complex-shaped HA ceramic and its composite scaffolds. Herein, this chapter introduces the latest advances of 3D printed HA ceramic and its composite scaffolds, including HA, HA/TCP, and various HA/polymer composite scaffolds. The performances of these scaffolds, including their mechanical properties, and in vitro and in vivo biological behaviors, are further summarized. Finally, the challenges and opportunities involved in this field are discussed and forecasted. It is believed this chapter can give some guidance for researchers or graduate students in the field of 3D printing of bioceramic scaffolds for tissue engineering.
Keywords: hydroxyapatite, scaffold, additive manufacturing, 3D printing, tissue engineering
Ahn Ji-Ho, Kim J, Han G, Kim DE, Cheon K-H, Lee H, Kim H-E, Kim Y-J, Jang TS and
Jung H-D. 2021. “3D-printed biodegradable composite scaffolds with significantly
enhanced mechanical properties via the combination of binder jetting and capillary
rise infiltration process.” Additive Manufacturing, 41.
Allen Nicholas B, Abar B, Johnson L, Burbano J, Danilkowicz RM and Adams SB. 2022.
“3D-bioprinted GelMA-gelatin-hydroxyapatite osteoblast-laden composite hydrogels
for bone tissue engineering.” Bioprinting, 26:1690-1698.
Ballouze R, Marahat MH, Mohamad S, Saidin NA, Kasim SR and Ooi JP. 2021.
“Biocompatible magnesium-doped biphasic calcium phosphate for bone
regeneration.” J Biomed Mater Res B Appl Biomater, 109 (10):1426-1435.
Batstone MD. 2018. “Reconstruction of major defects of the jaws.”
Aust Dent J, 63 Suppl 1:S108-S113. DOI: 10.1111/adj.12596.
Bedell ML, Navara AM, Du Y, Zhang S and Mikos AG. 2020. “Polymeric Systems for
Bioprinting.” Chem Rev, 120 (19):10744-10792. DOI: 10.1021/acs.chemrev.9b00834.
Chen Q, Zou B, Lai Q, Wang Y, Xue R, Xing H, Fu X, Huang C and Yao P. 2019. “A study
on biosafety of HAP ceramic prepared by SLA-3D printing technology directly.” J
Mech Behav Biomed Mater, 98:327-335. DOI: 10.1016/j.jmbbm.2019.06.031.
Cox SC, Thornby JA, Gibbons GJ, Williams MA and Mallick KK. 2015. “3D printing of
porous hydroxyapatite scaffolds intended for use in bone tissue engineering
applications.” Mater Sci Eng C Mater Biol Appl, 47:237-47.
Du Yao, Hu T, You J, Ye Y, Zhang B, Bao B, Li M, Liu Y, Wang Y and Wang T. 2021.
“Study of falling‐down‐type DLP 3D printing technology for high‐resolution
hydroxyapatite scaffolds.” International Journal of Applied Ceramic Technology, 19
(1):268-280. DOI: 10.1111/ijac.13915.
Fiume Elisa, Magnaterra G, Rahdar A, Verné E and Baino F. 2021. “Hydroxyapatite for
Biomedical Applications: A Short Overview.” Ceramics, 4 (4):542-563.
Frisbie David D, Oxford JT, Southwood L, Trotter GW, Rodkey WG, Steadman JR,
Goodnight JL and Wayne McIlwraith C. 2003. “Early Events in Cartilage Repair After
Subchondral Bone Microfracture.” Clinical Orthopaedics and Related Research®,
Helaehil JV, Lourenco CB, Huang B, Helaehil LV, de Camargo IX, Chiarotto GB,
Santamaria-Jr M, Bartolo M and Caetano GF. 2021. “In Vivo Investigation of
Polymer-Ceramic PCL/HA and PCL/beta-TCP 3D Composite Scaffolds and
Electrical Stimulation for Bone Regeneration.” Polymers, (Basel) 14 (1).
Janarthanan Gopinathan, Pillai MM, Kulasekaran SS, Rajendran S and Bhattacharyya A.
2019. “Engineered knee meniscus construct: understanding the structure and impact
of functionalization in 3D environment.” Polymer Bulletin, 77 (5):2611-2629.
Kang Jin-Ho, Sakthiabirami K, Jang K-J, Jang J-G, Oh G-J, Park C, Fisher JG and Park S-W. 2022.
“Mechanical and biological evaluation of lattice structured hydroxyapatite
scaffolds produced via stereolithography additive manufacturing.” Materials &
Design, 214. DOI: 10.1016/j.matdes.2021.110372.
Kijartorn P, Wongpairojpanich J, Thammarakcharoen F, Suwanprateeb J and Buranawat
B. 2022. “Clinical evaluation of 3D printed nano-porous hydroxyapatite bone graft for
alveolar ridge preservation: A randomized controlled trial.” J Dent Sci, 17 (1):194-203.
Kumar A, Nune KC and Misra RD. 2016. “Biological functionality of extracellular matrixornamented
three-dimensional printed hydroxyapatite scaffolds.” J Biomed Mater Res
A, 104 (6):1343-51. DOI: 10.1002/jbm.a.35664.
Le Gars Santoni B, Niggli L, Dolder S, Loeffel O, Sblendorio GA, Heuberger R, Maazouz
Y, Stahli C, Dobelin N, Bowen P, Hofstetter W and Bohner M. 2022. “Effect of minor
amounts of beta-calcium pyrophosphate and hydroxyapatite on the physico-chemical
properties and osteoclastic resorption of beta-tricalcium phosphate cylinders.” Bioact
Mater, 10:222-235. DOI: 10.1016/j.bioactmat.2021.09.003.
Lee Hoyeol, Yoo JM, Ponnusamy NK and Nam SY. 2022. “3D-printed hydroxyapatite/
gelatin bone scaffolds reinforced with graphene oxide: Optimized fabrication and
mechanical characterization.” Ceramics International, 48 (7):10155-10163.
Lim HK, Hong SJ, Byeon SJ, Chung SM, On SW, Yang BE, Lee JH and Byun SH. 2020.
“3D-Printed Ceramic Bone Scaffolds with Variable Pore Architectures.” Int J Mol Sci,
21 (18). DOI: 10.3390/ijms21186942.
Liu G, Zhang B, Wan T, Zhou C, Fan Y, Tian W and Jing W. 2022. “A 3D-printed biphasic
calcium phosphate scaffold loaded with platelet lysate/gelatin methacrylate to promote
vascularization.” J Mater Chem B, 10 (16):3138-3151. DOI: 10.1039/d2tb00006g.
Liu Ruoxi, Ma L, Liu H, Xu B, Feng C and He R. 2021. “Effects of pore size on the
mechanical and biological properties of stereolithographic 3D printed HAp
bioceramic scaffold.” Ceramics International, 47 (20):28924-28931.
Liu Shuifeng, Hu Y, Zhang J, Bao S, Xian L, Dong X, Zheng W, Li Y, Gao H and Zhou
W. 2019. “Bioactive and Biocompatible Macroporous Scaffolds with Tunable
Performances Prepared Based on 3D Printing of the Pre‐Crosslinked Sodium
Alginate/Hydroxyapatite Hydrogel Ink.” Macromolecular Materials and Engineering,
304 (4). DOI: 10.1002/mame.201800698.
Luo Y, Zhai D, Huan Z, Zhu H, Xia L, Chang J and Wu C. 2015. “Three-Dimensional
Printing of Hollow-Struts-Packed Bioceramic Scaffolds for Bone Regeneration.” ACS
Appl Mater Interfaces, 7 (43):24377-83. DOI: 10.1021/acsami.5b08911.
Miao F, Liu T, Zhang X, Wang X, Wei Y, Hu Y, Lian X, Zhao L, Chen W and Huang D.
2022. “Engineered bone tissues using biomineralized gelatin methacryloyl/sodium
alginate hydrogels.” J Biomater Sci Polym Ed, 33 (2):137-154.
Natarajan ABM, Sivadas VPD and Nair PD. 2021. “3D-printed biphasic scaffolds for the
simultaneous regeneration of osteochondral tissues.” Biomed Mater, 16 (5).
Nemcakova I, Litvinec A, Mandys V, Potocky S, Plencner M, Doubkova M, Nanka O,
Olejnickova V, Sankova B, Bartos M, Ukraintsev E, Babcenko O, Bacakova L,
Kromka A, Rezek B and Sedmera D. 2022. “Coating Ti6Al4V implants with
nanocrystalline diamond functionalized with BMP-7 promotes extracellular matrix
mineralization in vitro and faster osseointegration in vivo.” Sci Rep, 12 (1):5264.
Owida HA, Kuiper NL and Yang Y. 2021. “Maintenance and Acceleration of Pericellular
Matrix Formation within 3D Cartilage Cell Culture Models.” Cartilage, 13
(2_suppl):847S-861S. DOI: 10.1177/1947603519870839.
Ramesh N, Moratti SC and Dias GJ. 2018. “Hydroxyapatite-polymer biocomposites for
bone regeneration: A review of current trends.” J Biomed Mater Res B Appl Biomater,
106 (5):2046-2057. DOI: 10.1002/jbm.b.33950.
Ranga N, Gahlyan S and Duhan S. 2020. “Antibacterial Efficiency of Zn, Mg and Sr Doped
Bioactive Glass for Bone Tissue Engineering.” J Nanosci Nanotechnol, 20 (4):2465-2472.
Rh Owen G, Dard M and Larjava H. 2018. “Hydoxyapatite/beta-tricalcium phosphate
biphasic ceramics as regenerative material for the repair of complex bone defects.” J
Biomed Mater Res B Appl Biomater, 106 (6):2493-2512. DOI: 10.1002/jbm.b.34049.
Schmidleithner C, Malferarri S, Palgrave R, Bomze D, Schwentenwein M and Kalaskar
DM. 2019. “Application of high resolution DLP stereolithography for fabrication of
tricalcium phosphate scaffolds for bone regeneration.” Biomed Mater, 14 (4):045018.
Sommerfeldt DW and Rubin CT. 2001. “Biology of bone and how it orchestrates the form
and function of the skeleton.” Eur Spine J, 10 Suppl 2:S86-95.
Temple JP, Hutton DL, Hung BP, Huri PY, Cook CA, Kondragunta R, Jia X and Grayson
WL. 2014. “Engineering anatomically shaped vascularized bone grafts with hASCs
and 3D-printed PCL scaffolds.” J Biomed Mater Res A, 102 (12):4317-25.
Teotia AK, Dienel K, Qayoom I, van Bochove B, Gupta S, Partanen J, Seppala J and Kumar
A. 2020. “Improved Bone Regeneration in Rabbit Bone Defects Using 3D Printed
Composite Scaffolds Functionalized with Osteoinductive Factors.” ACS Appl Mater
Interfaces, 12 (43):48340-48356. DOI: 10.1021/acsami.0c13851.
Tikhonov A, Evdokimov P, Klimashina E, Tikhonova S, Karpushkin E, Scherbackov I,
Dubrov V and Putlayev V. 2020. “Stereolithographic fabrication of three-dimensional
permeable scaffolds from CaP/PEGDA hydrogel biocomposites for use as bone
grafts.” J Mech Behav Biomed Mater, 110:103922.
DOI: 10.1016/ j.jmbbm.2020.103922.
Wei J, Yan Y, Gao J, Li Y, Wang R, Wang J, Zou Q, Zuo Y, Zhu M and Li J. 2021.
“3D printed hydroxyapatite microspheres reinforced PLGA scaffolds for bone
regeneration.” Mater Sci Eng C Mater Biol Appl, 112618.
Wen Y, Xun S, Haoye M, Baichuan S, Peng C, Xuejian L, Kaihong Z, Xuan Y, Jiang P and
Shibi L. 2017. “3D printed porous ceramic scaffolds for bone tissue engineering: A
review.” Biomater Sci, 5 (9):1690-1698. DOI: 10.1039/c7bm00315c.
Yuan B, Wang Z, Zhao Y, Tang Y, Zhou S, Sun Y and Chen X. 2021. “In Vitro and In
Vivo Study of a Novel Nanoscale Demineralized Bone Matrix Coated PCL/beta-TCP
Scaffold for Bone Regeneration.” Macromol Biosci, 21 (3):e2000336.
Yuan M, Bi B, Huang J, Zhuo R and Jiang X. 2018. “Thermosensitive and
photocrosslinkable hydroxypropyl chitin-based hydrogels for biomedical
applications.” Carbohydr Polym, 192:10-18. DOI: 10.1016/j.carbpol.2018.03.031.
Zhang Ben and Song J. 2018. “3D-Printed Biomaterials for Guided Tissue Regeneration.”
Small Methods, 2 (9). DOI: 10.1002/smtd.201700306.
Zhang Xueqin, Zhang K, Zhang L, Wang W, Li Y and He R. 2022. “Additive
manufacturing of cellular ceramic structures: From structure to structure–function
integration.” Materials and Design, 215. DOI: 10.1016/j.matdes.2022.110470.
Zhang Y, Liu L, Li N, Wang Y and Yue X. 2022. “3D scaffold fabricated with composite
material for cell culture and its derived platform for safety evaluation of drugs.”
Toxicology, 466:153066. DOI: 10.1016/j.tox.2021.153066.
Zhao D, Witte F, Lu F, Wang J, Li J and Qin L. 2017. “Current status on clinical
applications of magnesium-based orthopaedic implants: A review from clinical
translational perspective.” Biomaterials, 112:287-302.