AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.3574
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RESEARCH ARTICLE

Double-protein-loaded 3D-printed polyetheretherketone cage for promoting interbody fusion via osteogenic differentiation

Feng Zheng1,2 ,  Xiaoqiang Gao1 ,  Sheng Chai2 ,  Haibin Lin1* ,  Huan Liu3*
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1 Department of Orthopedics, Affiliated Hospital of Putian University, Putian, Fujian, China
2 The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China
3 Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China
IJB, 3574 https://doi.org/10.36922/ijb.3574
Submitted: 5 May 2024 | Accepted: 14 June 2024 | Published: 29 July 2024
© 2024 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/ )
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Abstract

Intervertebral disc degeneration (IDD) is a common condition characterized by age-related wear and tear of the spine. In advanced stages or severe cases of IDD, surgical treatment involving the implantation of an interbody cage is often the primary treatment approach. Polyetheretherketone (PEEK) has been widely used in orthopedic and spinal implants due to its remarkable mechanical properties, biocompatibility, and corrosion resistance. However, when used in interbody cages, PEEK exhibits poor processability and biological inertness, which are significant disadvantages that need to be addressed. In this work, we first fabricated the PEEK cage via the fused deposition modeling (FDM) method. To improve its fusion effect, bone morphogenetic protein 2 (BMP2) was loaded onto sulfonated PEEK and sealed with gelatin/chitosan (Gel/Chi) multilayer films. Substance P was then grafted on the surface with a Schiff base. When the cage is implanted, substance P is released first, recruiting bone marrow-mesenchymal stem cells (MSCs) to the implant surface. Subsequently, upon degradation of the Gel/Chi multilayer films, BMP2 is slowly released and promotes osteogenic differentiation of MSCs. In vivo results revealed that the double-protein-loaded PEEK cage exhibited remarkable fusion effects. This work provides a novel approach for the design and fabrication of a PEEK intervertebral fusion device with an excellent fusion effect.

Keywords
Polyetheretherketone
3D printing
Interbody cage
Mesenchymal stem cell recruitment
Funding
This work was supported by the Sichuan Provincial Department of Science and Technology (grant number: 2023ZYD0072).
Conflict of interest
The authors declare no conflicts of interest.
References
  1. Song C, Hu P, Peng R, Li F, Fang Z, Xu Y. Bioenergetic dysfunction in the pathogenesis of intervertebral disc degeneration. Pharmacol Res. 2024;26:107119. doi: 10.1016/j.phrs.2024.107119
  2. Novais EJ, Narayanan R, Canseco JA, et al. A new perspective on intervertebral disc calcification-from bench to bedside. Bone Res. 2024;12(1):3. doi: 10.1038/s41413-023-00307-3
  3. Samanta A, Lufkin T, Kraus P. Intervertebral disc degeneration-current therapeutic options and challenges. Front Public Health. 2023;11:1156749. doi: 10.3389/fpubh.2023.1156749
  4. Tong W, Lu Z, Qin L, et al. Cell therapy for the degenerating intervertebral disc. Transl Res. 2017,181:49-58. doi: 10.1016/j.trsl.2016.11.008
  5. Kirnaz S, Capadona C, Wong T, et al. Fundamentals of intervertebral disc degeneration. World Neurosurg. 2022;157:264-273. doi: 10.1016/j.wneu.2021.09.066
  6. Xin J, Wang Y, Zheng Z, Wang S, Na S, Zhang S. Treatment of intervertebral disc degeneration. Orthop Surg. 2022;14(7):1271-1280. doi: 10.1111/os.13254
  7. Kos N, Gradisnik L, Velnar T. A brief review of the degenerative intervertebral disc disease. Med Arch. 2019;73(6):421-424. doi: 10.5455/medarh.2019.73.421-424
  8. Zhu C, He M, Mao L, et al. Titanium-interlayer mediated hydroxyapatite coating on polyetheretherketone: a prospective study in patients with single-level cervical degenerative disc disease. J Transl Med. 2021;19(1):14. doi: 10.1186/s12967-020-02688-z
  9. Kersten RF, van Gaalen SM, de Gast A, Öner FC. Polyetheretherketone (PEEK) cages in cervical applications: a systematic review. Spine J. 2015;15(6):1446-1460. doi: 10.1016/j.spinee.2013.08.030
  10. de Ruiter L, Rankin K, Browne M, Briscoe A, Janssen D, Verdonschot N. Decreased stress shielding with a PEEK femoral total knee prosthesis measured in validated computational models. J Biomech. 2021;118:110270. doi: 10.1016/j.jbiomech.2021.110270
  11. Zheng Z, Liu P, Zhang X, et al. Strategies to improve bioactive and antibacterial properties of polyetheretherketone (PEEK) for use as orthopedic implants. Mater Today Bio. 2022;16:100402. doi: 10.1016/j.mtbio.2022.100402
  12. Kurtz SM, Devine JN. PEEK biomaterials in trauma, orthopedic, and spinal implants. Biomaterials. 2007;28(32):4845-4869. doi: 10.1016/j.biomaterials.2007.07.013
  13. Li T, Song Z, Yang X, Du J. Influence of processing parameters on the mechanical properties of peek plates by hot compression molding. Materials (Basel). 2022;16(1):36. doi: 10.3390/ma16010036
  14. Yu D, Lei X, Zhu H. Modification of polyetheretherketone (PEEK) physical features to improve osteointegration. J Zhejiang Univ Sci B. 2022;23(3):189-203. doi: 10.1631/jzus.B2100622
  15. Zhang Z, Zhang X, Zheng Z, et al. Latest advances: improving the anti-inflammatory and immunomodulatory properties of PEEK materials. Mater Today Bio. 2023;22:100748. doi: 10.1016/j.mtbio.2023.100748
  16. Wang G, Han D, Cao Z, Guan H, Xuan T. Outcomes of autograft alone versus PEEK+ autograft interbody fusion in the treatment of adult lumbar isthmic spondylolisthesis. Clin Neurol Neurosurg. 2017;155:1-6. doi: 10.1016/j.clineuro.2017.01.020
  17. Wang L, Yang C, Sun C, et al. Fused deposition modeling PEEK implants for personalized surgical application: from clinical need to biofabrication. Int J Bioprint. 2022;8(4):615. doi: 10.18063/ijb.v8i4.615
  18. Wang Y, Müller WD, Rumjahn A, Schwitalla A. Parameters influencing the outcome of additive manufacturing of tiny medical devices based on PEEK. Materials (Basel). 2020;13(2):466. doi: 10.3390/ma13020466
  19. Rendas P, Figueiredo L, Machado C, Mourão A, Vidal C, Soares B. Mechanical performance and bioactivation of 3D-printed PEEK for high-performance implant manufacture: a review. Prog Biomater. 2023;12(2):89-111. doi: 10.1007/s40204-022-00214-6
  20. Florian B, Michel K, Steffi G, et al. MSC differentiation on two-photon polymerized, stiffness and BMP2 modified biological copolymers. Biomed Mater. 2019;14(3):035001. doi: 10.1088/1748-605X/ab0362
  21. Zhou N, Hu N, Liao JY, et al. HIF-1α as a regulator of BMP2-induced chondrogenic differentiation, osteogenic differentiation, and endochondral ossification in stem cells. Cell Physiol Biochem. 2015;36(1):44-60. doi: 10.1159/000374052
  22. Bedair TM, Lee CK, Kim DS, et al. Magnesium hydroxide-incorporated PLGA composite attenuates inflammation and promotes BMP2-induced bone formation in spinal fusion. J Tissue Eng. 2020;11:2041731420967591. doi: 10.1177/2041731420967591
  23. Mashaghi A, Marmalidou A, Tehrani M, Grace PM, Pothoulakis C, Dana R. Neuropeptide substance P and the immune response. Cell Mol Life Sci. 2016;73(22):4249-4264. doi: 10.1007/s00018-016-2293-z
  24. Sun T, Jiang X, Wang Q, et al. Substance P mediated DGLs complexing with DACHPt for targeting therapy of Glioma. ACS Appl Mater Interfaces. 2017;9(40):34603-34617. doi: 10.1021/acsami.7b05997
  25. Zieglgänsberger W. Substance P and pain chronicity. Cell Tissue Res. 2019;375(1):227-241. doi: 10.1007/s00441-018-2922-y
  26. Kim S, Piao J, Son Y, Hong HS. Substance P enhances proliferation and paracrine potential of adipose-derived stem cells in vitro. Biochem Biophys Res Commun. 2017;485(1):131-137. doi: 10.1016/j.bbrc.2017.02.036
  27. Bhatia M. H₂S and substance P in inflammation. Methods Enzymol. 2015;555:195-205. doi: 10.1016/bs.mie.2014.11.024
  28. Hong HS, Kim S, Jin Y, Son Y. Substance P enhances the therapeutic effect of MSCs by modulating their angiogenic potential. J Cell Mol Med. 2020;24(21):12560-12571. doi: 10.1111/jcmm.15804
  29. Kim SJ, Kim JE, Choe G, et al. Self-assembled peptide-substance P hydrogels alleviate inflammation and ameliorate the cartilage regeneration in knee osteoarthritis. Biomater Res. 2023;27(1):40. doi: 10.1186/s40824-023-00387-6
  30. Mu C, Hu Y, Hou Y, et al. Substance P-embedded multilayer on titanium substrates promotes local osseointegration via MSC recruitment. J Mater Chem B. 2020;8(6):1212-1222. doi: 10.1039/c9tb01124b
  31. Huang L, Luo Z, Hu Y, et al. Enhancement of local bone remodeling in osteoporotic rabbits by biomimic multilayered structures on Ti6Al4V implants. J Biomed Mater Res A. 2016;104(6):1437-1451. doi: 10.1002/jbm.a.35667
  32. Beierfuß A, Dietrich H, Kremser C, et al. Knockout of Apolipoprotein E in rabbit promotes premature intervertebral disc degeneration: a new in vivo model for therapeutic approaches of spinal disc disorders. PLoS One. 2017;12(11):e0187564. doi: 10.1371/journal.pone.0187564
  33. Pan M, Li Q, Li S, et al. Percutaneous endoscopic lumbar discectomy: indications and complications. Pain Physician. 2020; 23(1):49-56. doi: 10.36076/ppj.2020/23/49
  34. Perera K, Ivone R, Natekin E, Wilga CA, Shen J, Menon JU. 3D bioprinted implants for cartilage repair in intervertebral discs and knee menisci. Front Bioeng Biotechnol. 2022;9:754113. doi: 10.3389/fbioe.2021.754113
  35. Thavaneswaran P, Vandepeer M. Lumbar artificial intervertebral disc replacement: a systematic review. ANZ J Surg. 2014;84(3):121-127. doi: 10.1111/ans.12315
  36. Han X, Gao W, Zhou Z, et al. Application of biomolecules modification strategies on PEEK and its composites for osteogenesis and antibacterial properties. Colloids Surf B Biointerfaces. 2022;215:112492. doi: 10.1016/j.colsurfb.2022.112492
  37. Dua R, Rashad Z, Spears J, Dunn G, Maxwell M. Applications of 3D-printed PEEK via fused filament fabrication: a systematic review. Polymers (Basel). 2021;13(22):4046. doi: 10.3390/polym13224046
  38. Schönhoff LM, Mayinger F, Eichberger M, Reznikova E, Stawarczyk B. 3D printing of dental restorations: mechanical properties of thermoplastic polymer materials. J Mech Behav Biomed Mater. 2021;119:104544. doi: 10.1016/j.jmbbm.2021
  39. Zhang H, Duan M, Qin S, Zhang Z. Preparation and modification of porous polyetheretherketone (PEEK) cage material based on fused deposition modeling (FDM). Polymers (Basel). 2022;14(24):5403. doi: 10.3390/polym14245403
  40. Jung J, Jeong J, Hong HS. Substance P improves MSC-mediated RPE regeneration by modulating PDGF-BB. Biochem Biophys Res Commun. 2019;515(4):524-530. doi: 10.1016/j.bbrc.2019.05.186
  41. Kim JE, Lee JH, Kim SH, Jung Y. Skin regeneration with self-assembled peptide hydrogels conjugated with substance P in a diabetic rat model. Tissue Eng Part A. 2018; 24(1-2):21-33. doi: 10.1089/ten.TEA.2016.0517
  42. Zhang Y, An S, Hao J, Tian F, Fang X, Wang J. Systemic injection of substance P promotes murine calvarial repair through mobilizing endogenous mesenchymal stem cells. Sci Rep. 2018;8(1):12996. doi: 10.1038/s41598-018-31414-5

 

 

 

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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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