Regulation of Immune Microenvironments by Polyetheretherketone Surface Topography for Improving Osseointegration

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2025 Mar 12

PMID 40069791

Authors

Yuqing Zhao

Yanxin An

Fan Wu

Lipeng Liu

Franklin R Tay

Yang Jiao

Jing Wang

Affiliations

Soon will be listed here.

Abstract

Optimizing the immune microenvironment is essential for successful implant osseointegration. In this study, four different nano/microstructures were fabricated on polyetheretherketone (PEEK) substrates by varying the agitation speed during sulfonation to influence osteoimmunomodulation and implant integration. The results indicate that nano/microstructures with minimal dimensions (SP450) inhibit actin polymerization by reducing calcium influx through PIEZO1, activating the anti-inflammatory M2 macrophage phenotype. Among the tested specimens, SP450 exhibited the lowest expression levels of tumor necrosis factor-α and interleukin-1β while releasing the highest levels of anti-inflammatory factors, including interleukin-4 and interleukin-10. This optimized immune environment promotes the osteogenesis of MC3T3-E1 pre-osteoblasts and enhances the osseointegration of PEEK implants. Transcriptomic analysis and validation experiment further revealed that SP450 inhibits osteoclastic differentiation by down-regulating transforming growth factor-β2 and suppressing the NF-κB signaling pathway. These findings suggest that manipulating the surface topography of PEEK implants is an effective strategy for enhancing osseointegration with promising clinical applications.

References

Qi H, Shi M, Ni Y, Mo W, Zhang P, Jiang S . Size-Confined Effects of Nanostructures on Fibronectin-Induced Macrophage Inflammation on Titanium Implants. Adv Healthc Mater. 2021; 10(20):e2100994. DOI: 10.1002/adhm.202100994. View

Pergola C, Schubert K, Pace S, Ziereisen J, Nikels F, Scherer O . Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy. Sci Rep. 2017; 7:41434. PMC: 5278352. DOI: 10.1038/srep41434. View

Zheng Z, Liu P, Zhang X, Xin J, Wang Y, Zou X . Strategies to improve bioactive and antibacterial properties of polyetheretherketone (PEEK) for use as orthopedic implants. Mater Today Bio. 2022; 16:100402. PMC: 9466655. DOI: 10.1016/j.mtbio.2022.100402. View

Ma R, Wang J, Li C, Ma K, Wei J, Yang P . Effects of different sulfonation times and post-treatment methods on the characterization and cytocompatibility of sulfonated PEEK. J Biomater Appl. 2020; 35(3):342-352. DOI: 10.1177/0885328220935008. View

Wu Q, Zhou X, Huang D, Ji Y, Kang F . IL-6 Enhances Osteocyte-Mediated Osteoclastogenesis by Promoting JAK2 and RANKL Activity In Vitro. Cell Physiol Biochem. 2017; 41(4):1360-1369. DOI: 10.1159/000465455. View

Fennen M, Pap T, Dankbar B . Smad-dependent mechanisms of inflammatory bone destruction. Arthritis Res Ther. 2016; 18(1):279. PMC: 5134126. DOI: 10.1186/s13075-016-1187-7. View

Liu X, Zhang H, Yan B, Yeung K, Liao Y, Ouyang L . On-Off Phagocytosis and Switchable Macrophage Activation Stimulated with NIR for Infected Percutaneous Tissue Repair of Polypyrrole-Coated Sulfonated PEEK. Adv Sci (Weinh). 2022; 10(5):e2205048. PMC: 9929275. DOI: 10.1002/advs.202205048. View

Liang B, Wang H, Wu D, Wang Z . Macrophage M1/M2 polarization dynamically adapts to changes in microenvironment and modulates alveolar bone remodeling after dental implantation. J Leukoc Biol. 2021; 110(3):433-447. DOI: 10.1002/JLB.1MA0121-001R. View

Atcha H, Jairaman A, Holt J, Meli V, Nagalla R, Veerasubramanian P . Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nat Commun. 2021; 12(1):3256. PMC: 8167181. DOI: 10.1038/s41467-021-23482-5. View

10.

Shirazi S, Ravindran S, Cooper L . Topography-mediated immunomodulation in osseointegration; Ally or Enemy. Biomaterials. 2022; 291:121903. PMC: 10148651. DOI: 10.1016/j.biomaterials.2022.121903. View

11.

Pan H, Xie Y, Zhang Z, Li K, Hu D, Zheng X . Immunomodulation effect of a hierarchical macropore/nanosurface on osteogenesis and angiogenesis. Biomed Mater. 2017; 12(4):045006. DOI: 10.1088/1748-605X/aa6b7c. View

12.

Li Y, Wang J, He D, GuoxiongZhu , Wu G, Chen L . Surface sulfonation and nitrification enhance the biological activity and osteogenesis of polyetheretherketone by forming an irregular nano-porous monolayer. J Mater Sci Mater Med. 2019; 31(1):11. DOI: 10.1007/s10856-019-6349-0. View

13.

Xu Y, Xu Y, Zhu Y, Sun H, Juguilon C, Li F . Macrophage miR-34a Is a Key Regulator of Cholesterol Efflux and Atherosclerosis. Mol Ther. 2019; 28(1):202-216. PMC: 6952168. DOI: 10.1016/j.ymthe.2019.09.008. View

14.

Yu Y, Wu J, Lin C, Qin X, Tay F, Miao L . Elimination of methicillin-resistant Staphylococcus aureus biofilms on titanium implants via photothermally-triggered nitric oxide and immunotherapy for enhanced osseointegration. Mil Med Res. 2023; 10(1):21. PMC: 10158155. DOI: 10.1186/s40779-023-00454-y. View

15.

Junkar I, Kulkarni M, Drasler B, Rugelj N, Mazare A, Flasker A . Influence of various sterilization procedures on TiO2 nanotubes used for biomedical devices. Bioelectrochemistry. 2016; 109:79-86. DOI: 10.1016/j.bioelechem.2016.02.001. View

16.

Deng R, Zou M, Zheng D, Peng S, Liu W, Bai X . Nanoparticles from Cuttlefish Ink Inhibit Tumor Growth by Synergizing Immunotherapy and Photothermal Therapy. ACS Nano. 2019; 13(8):8618-8629. DOI: 10.1021/acsnano.9b02993. View

17.

Zhao Y, Bai L, Zhang Y, Yao R, Sun Y, Hang R . Type I collagen decorated nanoporous network on titanium implant surface promotes osseointegration through mediating immunomodulation, angiogenesis, and osteogenesis. Biomaterials. 2022; 288:121684. DOI: 10.1016/j.biomaterials.2022.121684. View

18.

Xie L, Wang G, Wu Y, Liao Q, Mo S, Ren X . Programmed surface on poly(aryl-ether-ether-ketone) initiating immune mediation and fulfilling bone regeneration sequentially. Innovation (Camb). 2021; 2(3):100148. PMC: 8454576. DOI: 10.1016/j.xinn.2021.100148. View

19.

Wang J, Meng F, Song W, Jin J, Ma Q, Fei D . Nanostructured titanium regulates osseointegration via influencing macrophage polarization in the osteogenic environment. Int J Nanomedicine. 2018; 13:4029-4043. PMC: 6045901. DOI: 10.2147/IJN.S163956. View

20.

Kitaura H, Marahleh A, Ohori F, Noguchi T, Shen W, Qi J . Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption. Int J Mol Sci. 2020; 21(14). PMC: 7404053. DOI: 10.3390/ijms21145169. View