DOI:

10.37988/1811-153X_2026_1_178

Immunohistochemical characterization of local tissue reactions to the implantation of highly porous implants based on polyetheretherketone and polymethylmethacrylate

Authors

  • G.A. Demyashkin 1, Doctor of Science in Medicine, pathologist, leading researcher at the Scientific and Educational Resource Center for Innovative Technologies of Molecular Morphology
    ORCID: 0000-0001-8447-2600
  • M.Yu. Durasov 1, postgraduate student of the Maxillofacial surgery and surgical dentistry Department
    ORCID: 0009-0008-7880-8591
  • A.A. Muraev 1, Doctor of Science in Medicine, professor of the Maxillofacial surgery and surgical dentistry Department
    ORCID: 0000-0003-3982-5512
  • K.A. Silakov 1, junior researcher of the Scientific and Educational Resource Center for Innovative Technologies of Molecular Morphology
    ORCID: 0009-0000-2073-3699
  • D.Yu. Milyukova 2, researcher of the Surgical Dentistry and Maxillofacial surgery Department
    ORCID: 0000-0001-5223-8481
  • S.Yu. Ivanov 1, 2, Russian Academy of Science corresponding member, Doctor of Science in Medicine, full professor of the Maxillofacial surgery and surgical dentistry Department; full professor of the Maxillofacial surgery Department
    ORCID: 0000-0001-5458-0192
  • G.E. Dzhendzhera 3, researcher
    ORCID: 0009-0003-7331-7156
  • A.A. Ushakov 3, researcher
    ORCID: 0000-0003-3563-6001
  • 1 RUDN University, 117198, Moscow, Russia
  • 2 Sechenov University, 119991, Moscow, Russia
  • 3 “Bonabyte” LLC, 125284, Moscow, Russia

Abstract

The development of biocompatible implant materials remains a key priority in modern maxillofacial surgery and dental practice. This study presents an evaluation of tissue responses to subcutaneous implantation of 3D-printed constructs made from polyetheretherketone (PEEK) and polymethylmethacrylate (PMMA). A morphological and immunohistochemical analysis was performed at various time points after implantation, using markers such as CD3, CD20, VEGF, and Collagen I. The findings revealed differences in inflammatory response, angiogenesis, and fibrosis depending on the material composition. The results confirm the high biocompatibility of PEEK and highlight its potential for use in reconstructive surgery. Objective: To assess the immunohistochemical response of local tissues following subcutaneous implantation of PEEK and PMMA-based materials, and to determine their biocompatibility for clinical applications.
Materials and methods.
Soft tissue samples were obtained from experimental animals after subcutaneous implantation of implants made from four different polymers. Morphological and immunohistochemical analyses were conducted using antibodies to CD3, CD20, VEGF, and Collagen I. Quantitative assessment was performed within standardized microscopic fields.
Results.
The study revealed differences in the inflammatory response, angiogenesis, and fibrosis depending on the material composition. The findings confirm the high biocompatibility of PEEK and demonstrate its potential for use in reconstructive surgery. Mild inflammatory reaction was observed near all implant types; however, the PEEK group exhibited the most stable tissue response, with CD3+ cell density corresponding to 1—2 scores and stable VEGF levels (2—3 scores) throughout the observation period. In contrast, the PMMA group showed a more pronounced immune response, particularly on day 7, where CD3+ lymphocyte density reached 3 scores, exceeding the PEEK group by 2.8-fold (p<0.05); increased expression of VEGF and Collagen I (up to 3 scores) was also observed, followed by a decrease by day 60.
Conclusion.
The results demonstrate the high biocompatibility and low immunogenicity of PEEK, supporting its use as a preferred implant material. PMMA-based materials may elicit stronger tissue reactions and warrant further investigation and surface optimization.

Key words:

PEEK, PMMA, biocompatibility, immunohistochemistry, implants, inflammation, 3D printing

For Citation

[1]
Demyashkin G.A., Durasov M.Yu., Muraev A.A., Silakov K.A., Milyukova D.Yu., Ivanov S.Yu., Dzhendzhera G.E., Ushakov A.A. Immunohistochemical characterization of local tissue reactions to the implantation of highly porous implants based on polyetheretherketone and polymethylmethacrylate. Clinical Dentistry (Russia).  2026; 29 (1): 178—186. DOI: 10.37988/1811-153X_2026_1_178

References

  1. Punchak M., Chung L.K., Lagman C., Bui T.T., Lazareff J., Rezzadeh K., Jarrahy R., Yang I. Outcomes following polyetheretherketone (PEEK) cranioplasty: Systematic review and meta-analysis. J Clin Neurosci. 2017; 41: 30—35. PMID: 28377284
  2. Todaro M., Saponaro G., Perquoti F., Gasparini G., Signorelli F., Tartaglione T., Moro A. Bone regeneration and polyetheretherketone implants in maxillo-facial surgery and neurosurgery: A multidisciplinary study. Biology (Basel). 2024; 13 (7): 467. PMID: 39056662
  3. Elnaggar M.A., Elnoamany H.A., Eissa M.K. Clinical evaluation of 3D PEEK implants for skull bone defects repair: a single center case serious. Egyptian Journal of Neurosurgery. 2025; 1: 11. DOI: 10.1186/s41984-025-00374-0
  4. Markarov A.E., Eremin D.A., Martirosov A.V., Khandzratsyan A.S., Orazvaliev A.I., Bugayan S.A., Khalifaev O.I. Statistical analysis of data on emergency maxillofacial surgery. Bulletin of Russian State Medical University. 2023; (5): 56—62 (In Russian). DOI: 10.24075/brsmu.2023.038
  5. Gummadidala P. Complications in dental implantology. International Journal of Innovative Science and Research Technology (IJISRT). 2023; 8 (8): 2269—2276. DOI: 10.5281/zenodo.8334389
  6. Pituru S.M., Greabu M., Totan A., Imre M., Pantea M., Spinu T., Tancu A.M.C., Popoviciu N.O., Stanescu I.I., Ionescu E. A review on the biocompatibility of PMMA-based dental materials for interim prosthetic restorations with a glimpse into their modern manufacturing techniques. Materials (Basel). 2020; 13 (13): 2894. PMID: 32605174
  7. Xie W., Yang Z., Zhou Y., Xu X., Hu K. Research progress of 3D bioprinting PEEK scaffold material for bone regeneration. In: proceedings of 14th China Academic Conference on Printing and Packaging. Singapore: Springer Nature, 2024. Pp. 136—144. DOI: 10.1007/978-981-99-9955-2_19
  8. Pöppe J.P., Spendel M., Griessenauer C.J., Gaggl A., Wurm W., Enzinger S. Point-of-care 3-dimensional-printed polyetheretherketone customized implants for cranioplastic surgery of large skull defects. Oper Neurosurg. 2024; 27 (4): 449—454. PMID: 39283099
  9. Sumarno S., Trisanti P.N., Airlangga B., Kurniasari N.M.W., Hidayat R.A., Nisa A.C., Hernugrahanto K.D., Ferdiansyah M. Setting properties along bone cement preparation and its effect on material properties. Advanced Materials Research. 2024; 1179: 19—23. DOI: 10.4028/p-mxmms2
  10. Fons-Badal C., Labaig-Rueda C., Agustín-Panadero R., Solá-Ruiz M.F., Roig-Vanaclocha A., Fernández-Estevan L., Fons-Font A. Retrospective study of the association between peri-implantitis and keratinized mucosa. Applied Sciences (Switzerland). 2022; 14: 6980. DOI: 10.3390/app12146980
  11. Williams D.F. On the mechanisms of biocompatibility. Biomaterials. 2008; 29 (20): 2941—53. PMID: 18440630
  12. Milinkovic I., Krasavcevic A.D., Jankovic S., Sopta J., Aleksic Z. Immunohistochemical analysis of soft tissue response to polyetheretherketone (PEEK) and titanium healing abutments on dental implants: a randomized pilot clinical study. BMC Oral Health. 2022; 22 (1): 484. PMID: 36368972
  13. Rakic M., Canullo L., Radovanovic S., Tatic Z., Radunovic M., Souedain A., Weiss P., Struillou X., Vojvodic D. Diagnostic value of VEGF in peri-implantitis and its correlation with titanium particles: A controlled clinical study. Dent Mater. 2024; 40 (1): 28—36. PMID: 37865576
  14. Batool F., Özçelik H., Stutz C., Gegout P.Y., Benkirane-Jessel N., Petit C., Huck O. Modulation of immune-inflammatory responses through surface modifications of biomaterials to promote bone healing and regeneration. J Tissue Eng. 2021; 12: 20417314211041428. PMID: 34721831
  15. Roch T., Hahne S., Kratz K., Ma N., Lendlein A. Transparent substrates prepared from different amorphous polymers can directly modulate primary human B cell functions. Biotechnol J. 2017; 12: 1700334. PMID: 28857458
  16. Torstrick F.B., Lin A.S.P., Potter D., Safranski D.L., Sulchek T.A., Gall K., Guldberg R.E. Porous PEEK improves the bone-implant interface compared to plasma-sprayed titanium coating on PEEK. Biomaterials. 2018; 185: 106—116. PMID: 30236838
  17. Saghiri M.A., Asatourian A., Garcia-Godoy F., Sheibani N. A new era considering inorganic trace elements and biological activity of dental biomaterials (angiogenic activity). Acta Biomater Odontol Scand. 2016; 2 (1): 93—94. PMID: 28642917
  18. Chen Z., Chen Y., Wang Y., Deng J., Wang X., Wang Q., Liu Y., Ding J., Yu L. Polyetheretherketone implants with hierarchical porous structure for boosted osseointegration. Biomater Res. 2023; 27 (1): 61. PMID: 37370127

Received

October 9, 2025

Accepted

March 13, 2026

Published on

March 31, 2026