AccScience Publishing / IJB / Volume 10 / Issue 1 / DOI: 10.36922/ijb.1152
RESEARCH ARTICLE

Low-temperature deposition 3D printing biotin-doped PLGA/β-TCP scaffold for repair of bone defects in osteonecrosis of femoral head

Peng Xue1,2 Xiaoxue Tan3 Hongzhong Xi1,2 Hao Chen1,2 Shuai He1,2 Guangquan Sun1,2 Changyuan Gu1,2 Xiaohong Jiang3 Bin Du1,2* Xin Liu1,2*
Show Less
1 Department of Orthopedics, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
2 Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, China
3 International Chinese-Belorussian Scientific Laboratory on Vacuum-Plasma Technology, Nanjing University of Science and Technology, Nanjing 210094, China
IJB 2024, 10(1), 1152 https://doi.org/10.36922/ijb.1152
Submitted: 26 June 2023 | Accepted: 10 August 2023 | Published: 12 September 2023
(This article belongs to the Special Issue Biomedical application of 3D Bioprinting)
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

The removal of necrotic bone and implantation of bone repair materials is an effective treatment for osteonecrosis of the femoral head (ONFH)-type bone defects, but there are currently no clinically applicable bone repair materials. In this study, a biotin-doped bone repair scaffold was created using low-temperature deposition (LTD) three-dimensional (3D) printing technology, and its ability to repair bone defects in ONFH was evaluated. The scaffold was characterized in vitro, and its cytotoxicity and osteogenic capacity were assessed by co-culturing the scaffold with rat bone marrow mesenchymal stem cells. The scaffolds were implanted in an animal model of ONFH-type bone defects, and the effect of scaffolds on promoting bone repair was evaluated by means of radiology and histopathology. LTD 3D-printed biotin-doped scaffolds showed cancellous bone-like structures without inducing cytotoxicity, whereas high-biotin β-TCP scaffolds (HBPT; containing 2% biotin) promoted osteogenic differentiation more effectively. Experiments on animals revealed that the effect of HBPT on bone repair was significantly superior to that of other groups. The in vivo biocompatibility of HBPT was confirmed by blood analysis and hematoxylin and eosin staining of the main organs. In conclusion, biotin-doped scaffolds can be used to treat ONFH-type bone defects by virtue of their ability in promoting bone regeneration.

Keywords
Biotin
Low-temperature deposition
Bone repair
Osteonecrosis of the femoral head
Bone tissue engineering scaffold
Funding
This research was funded by National Natural Science Foundation of China (No. 82074471), Jiangsu Provincial Commission of Health and Family Planning (No. K2019027), Priority Academic Program Development of Jiangsu Higher Education Institutions (No. 035062005001), and Jiangsu Graduate Practice and Innovation Plan (No. SJCX22_0769).
Conflict of interest
The authors declare no conflicts of interest.
References
  1. Zhao D, Zhang F, Wang B, et al. Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version). J Orthop Translat. 2020;21(2020):100–110. doi: 10.1016/j.jot.2019.12.004
  2. Cui Q, Jo WL, Koo KH, et al. ARCO consensus on the pathogenesis of non-traumatic osteonecrosis of the femoral head. J Korean Med Sci. 2021;36(10):e65. doi: 10.3346/jkms.2021.36.e65
  3. Chen K, Liu Y, He J, et al. Steroid-induced osteonecrosis of the femoral head reveals enhanced reactive oxygen species and hyperactive osteoclasts. Int J Biol Sci. 2020;16(11):1888–1900. doi: 10.7150/ijbs.40917
  4. Xue P, Chen H, Xi H, et al. Magnesium dopped calcium-fluoride/icaritin composite multi-layer coating functionalized 3D printed β-TCP scaffold inducessustained bone regeneration in a rabbit model. Mater Des. 2022;223(111156):111156. doi: 10.1016/j.matdes.2022.111156
  5. Yuan P, Liu X, Du B, Sun GQ, Wang X, Lin XY. Mid- to long-term results of modified avascular fibular grafting for ONFH. J Hip Preserv Surg. 2021;8(3):274–281. doi: 10.1093/jhps/hnab046
  6. Bavya DK, Lalzawmliana V, Saidivya M, Kumar V, Roy M, Nandi SK. Magnesium phosphate bioceramics for bone tissue engineering. Chem Rec. 2022;22(11):e202200136. doi: 10.1002/tcr.202200136
  7. Nabiyouni M, Brückner T, Zhou H, Gbureck U, Bhaduri SB. Magnesium-based bioceramics in orthopedic applications. Acta Biomater. 2018;66(2018):23–43. doi: 10.1016/j.actbio.2017.11.033
  8. Baldwin P, Li DJ, Auston DA, Mir HS, Yoon RS, Koval KJ. Autograft, allograft, and bone graft substitutes: Clinical evidence and indications for use in the setting of orthopaedic trauma surgery. J Orthop Trauma. 2019;33(4):203–213. doi: 10.1097/BOT.0000000000001420
  9. Zhou Q, Su X, Wu J, et al. Additive manufacturing of bioceramic implants for restoration bone engineering: Technologies, advances, and future perspectives. ACS Biomater Sci Eng. 2023;9(3):1164–1189. doi: 10.1021/acsbiomaterials.2c01164
  10. Chen X, Tan B, Bao Z, et al. Enhanced bone regeneration via spatiotemporal and controlled delivery of a genetically engineered BMP-2 in a composite hydrogel. Biomaterials. 2021;277(2021):121117. doi: 10.1016/j.biomaterials.2021.121117
  11. Hong KS, Kim EC, Bang SH, et al. Bone regeneration by bioactive hybrid membrane containing FGF2 within rat calvarium. J Biomed Mater Res A. 2010;94(4): 1187–1194. doi: 10.1002/jbm.a.32799
  12. León-Del-Río A. Biotin in metabolism, gene expression, and human disease. J Inherit Metab Dis. 2019;42(4):647–654. doi: 10.1002/jimd.12073
  13. Bain SD, Newbrey JW, Watkins BA. Biotin deficiency may alter tibiotarsal bone growth and modeling in broiler chicks. Poult Sci. 1988;67(4):590–595. doi: 10.3382/ps.0670590
  14. Mock DM. Biotin: From nutrition to therapeutics. J Nutr. 2017;147(8):1487–1492. doi: 10.3945/jn.116.238956
  15. Dai Z, Koh WP. B-vitamins and bone health--a review of the current evidence. Nutrients. 2015;7(5):3322–3346. doi: 10.3390/nu7053322
  16. Cao J, Yang B, Yarmolenka MA, et al. Osteogenic potential evaluation of biotin combined with magnesium-doped hydroxyapatite sustained-release film. Mater Sci Eng C Mater Biol Appl. 2022;135(2022):112679. doi: 10.1016/j.msec.2022.112679
  17. Cheng T, Cao J, Wu T, et al. Study on osteoinductive activity of biotin film by low-energy electron beam deposition. Biomater Adv. 2022;135(2022):212730. doi: 10.1016/j.bioadv.2022.212730
  18. Nobles KP, Janorkar AV, Williamson RS. Surface modifications to enhance osseointegration-Resulting material properties and biological responses. J Biomed Mater Res B Appl Biomater. 2021;109(11):1909–1923. doi: 10.1002/jbm.b.34835
  19. Liu W, Wang D, Huang J, et al. Low-temperature deposition manufacturing: A novel and promising rapid prototyping technology for the fabrication of tissue-engineered scaffold. Mater Sci Eng C Mater Biol Appl. 2017;70(Pt 2):976–982. doi: 10.1016/j.msec.2016.04.014
  20. Su X, Wang T, Guo S. Applications of 3D printed bone tissue engineering scaffolds in the stem cell field. Regen Ther. 2021;16(2021):63–72. doi: 10.1016/j.reth.2021.01.007
  21. Parulski C, Jennotte O, Lechanteur A, Evrard B. Challenges of fused deposition modeling 3D printing in pharmaceutical applications: Where are we now. Adv Drug Deliv Rev. 2021;175(2021):113810. doi: 10.1016/j.addr.2021.05.020
  22. Xu M, Li Y, Suo H, et al. Fabricating a pearl/PLGA composite scaffold by the low-temperature deposition manufacturing technique for bone tissue engineering. Biofabrication. 2010;2(2):025002. doi: 10.1088/1758-5082/2/2/025002
  23. Zhang T, Zhang H, Zhang L, et al. Biomimetic design and fabrication of multilayered osteochondral scaffolds by low-temperature deposition manufacturing and thermal-induced phase-separation techniques. Biofabrication. 2017;9(2):025021. doi: 10.1088/1758-5090/aa7078
  24. Gao X, Wang H, Luan S, Zhou G. Low-temperature printed hierarchically porous induced-biomineralization polyaryletherketone scaffold for bone tissue engineering. Adv Healthc Mater. 2022;11(18): e2200977. doi: 10.1002/adhm.202200977
  25. Lian M, Sun B, Han Y, et al. A low-temperature-printed hierarchical porous sponge-like scaffold that promotes cell-material interaction and modulates paracrine activity of MSCs for vascularized bone regeneration. Biomaterials. 2021;274 (2021):120841. doi: 10.1016/j.biomaterials.2021.120841
  26. Liu Z, Feng X, Wang H, et al. Carbon nanotubes as VEGF carriers to improve the early vascularization of porcine small intestinal submucosa in abdominal wall defect repair. Int J Nanomedicine. 2014;9(2014):1275–1286. doi: 10.2147/IJN.S58626
  27. Ma J, Sun Y, Zhou H, et al. Animal models of femur head necrosis for tissue engineering and biomaterials research. Tissue Eng Part C Methods. 2022;28(5):214–227. doi: 10.1089/ten.TEC.2022.0043
  28. Wang H, Zhang Y, Ren C, et al. Biomechanical properties and clinical significance of cancellous bone in proximal femur: A review. Injury. 2023;54(6):1432–1438. doi: 10.1016/j.injury.2023.03.010
  29. Kang D, Lee YB, Yang GH, et al. FeS(2)-incorporated 3D PCL scaffold improves new bone formation and neovascularization in a rat calvarial defect model. Int J Bioprint. 2023;9(1): 636. doi: 10.18063/ijb.v9i1.636
  30. Guo L, Liang Z, Yang L, et al. The role of natural polymers in bone tissue engineering. J Control Release. 2021;338(2021):571–582. doi: 10.1016/j.jconrel.2021.08.055
  31. Yoon BH, Mont MA, Koo KH, et al. The 2019 Revised Version of Association Research Circulation Osseous Staging System of Osteonecrosis of the Femoral Head. J Arthroplasty. 2020;35(4):933–940. doi: 10.1016/j.arth.2019.11.029
  32. Liu LH, Zhang QY, Sun W, Li ZR, Gao FQ. Corticosteroid-induced osteonecrosis of the femoral head: Detection, diagnosis, and treatment in earlier stages. Chin Med J (Engl). 2017;130(21):2601–2607. doi: 10.4103/0366-6999.217094
Share
Back to top
International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing