Evaluation of the NanoGraft biomaterial immunogenicity in maxillary sinus augmentation
DOI:
https://doi.org/10.14739/2310-1210.2025.6.335692Keywords:
bone composite, immunogenicity, subantral augmentation, macrophages, osteogenesis, angiogenesisAbstract
Aim. This study aimed to evaluate the immunogenicity of the Nano Graft biomaterial in biopsies obtained from the maxillary sinus augmentation zone using morphological and immunohistochemical assessment of the cellular response.
Materials and methods. The study included 22 patients with partial posterior edentulism who underwent open maxillary sinus floor elevation using the Nano Graft biomaterial. Biopsy samples collected at the time of implant placement were fixed, decalcified, and processed for histological and immunohistochemical analysis with the following markers: CD8 (cytotoxic T lymphocytes), FOXP3 (regulatory T cells), CD68 (macrophages/osteoclasts), CD163 (M2 macrophages), SATB2 (osteogenic cells), and CD34 (endothelial cells). Inflammatory activity was assessed using a semi-quantitative scale.
Results. Histological examination revealed fibrous connective tissue containing fibroblasts, microvascular structures, and signs of osteon formation and bone remodeling. Immunohistochemistry demonstrated a low-grade lymphohistiocytic infiltrate with scarce CD8+ cells and no detectable FOXP3+ regulatory T cells, indicating the absence of a pronounced immune response. An abundant presence of CD163+ M2 macrophages suggested polarization toward a regenerative phenotype. Strong SATB2 expression confirmed osteoinductive activity, while numerous CD34+ endothelial cells indicated active angiogenesis.
Conclusions. The Nano Graft biomaterial exhibited low immunogenicity, characterized by a mild CD8+ T-cell response, absence of FOXP3+ regulatory T cells, and predominance of anti-inflammatory M2 macrophages. Its osteogenic potential and pro-angiogenic effects support its biocompatibility and clinical applicability for maxillary sinus augmentation.
References
- Baj A, Trapella G, Lauritano D, Candotto V, Mancini GE, Giannì AB. An overview on bone reconstruction of atrophic maxilla: success parameters and critical issues. J Biol Regul Homeost Agents. 2016 Apr-Jun;30(2 Suppl 1):209-15.
- Solakoglu Ö, Götz W, Heydecke G, Schwarzenbach H. Histological and immunohistochemical comparison of two different allogeneic bone grafting materials for alveolar ridge reconstruction: A prospective randomized trial in humans. Clin Implant Dent Relat Res. 2019;21(5):1002-16. doi: https://doi.org/10.1111/cid.12824
- Fretwurst T, Gad LM, Steinberg T, Schmal H, Zeiser R, Amler AK, et al. Detection of major histocompatibility complex molecules in processed allogeneic bone blocks for use in alveolar ridge reconstruction. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018:S2212-4403(18)30054-3. doi: https://doi.org/10.1016/j.oooo.2018.01.018
- Yang F, Liu H, Wei Y, Xue R, Liu Z, Chu X, Tian X, Yin L, Tang H. Antibacterial brush polypeptide coatings with anionic backbones. Acta Biomater. 2023 Jan 1;155:359-369. doi: https://doi.org/10.1016/j.actbio.2022.11.020
- Yu H, Tian Y, Wang Y, Mineishi S, Zhang Y. Dendritic Cell Regulation of Graft-Vs.-Host Disease: Immunostimulation and Tolerance. Front Immunol. 2019;10:93. doi: https://doi.org/10.3389/fimmu.2019.00093
- Zhang Y, Louboutin JP, Zhu J, Rivera AJ, Emerson SG. Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease. J Clin Invest. 2002;109(10):1335-44. doi: https://doi.org/10.1172/JCI14989
- Gu Q, Yang H, Shi Q. Macrophages and bone inflammation. J Orthop Translat. 2017;10:86-93. doi: https://doi.org/10.1016/j.jot.2017.05.002
- Baht GS, Vi L, Alman BA. The Role of the Immune Cells in Fracture Healing. Curr Osteoporos Rep. 2018;16(2):138-45. doi: https://doi.org/10.1007/s11914-018-0423-2
- Murray PJ, Wynn TA. Obstacles and opportunities for understanding macrophage polarization. J Leukoc Biol. 2011;89(4):557-63. doi: https://doi.org/10.1189/jlb.0710409
- Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011;11(11):723-37. doi: https://doi.org/10.1038/nri3073
- Chow SK, Wong CH, Cui C, Li MM, Wong RM, Cheung WH. Modulating macrophage polarization for the enhancement of fracture healing, a systematic review. J Orthop Translat. 2022;36:83-90. doi: https://doi.org/10.1016/j.jot.2022.05.004
- Schlundt C, El Khassawna T, Serra A, Dienelt A, Wendler S, Schell H, et al. Macrophages in bone fracture healing: Their essential role in endochondral ossification. Bone. 2018;106:78-89. doi: https://doi.org/10.1016/j.bone.2015.10.019
- Li J, Qu Y, Chu B, Wu T, Pan M, Mo D, et al. Research Progress on Biomaterials with Immunomodulatory Effects in Bone Regeneration. Adv Sci (Weinh). 2025 Sep;12(33):e01209. doi: https://doi.org/10.1002/advs.202501209
- Stout RD, Suttles J. Functional plasticity of macrophages: reversible adaptation to changing microenvironments. J Leukoc Biol. 2004;76(3):509-13. doi: https://doi.org/10.1189/jlb.0504272
- Jewell CM, Collier JH. Biomaterial interactions with the immune system. Biomater Sci. 2019 Feb 26;7(3):713-714. doi: https://doi.org/10.1039/c8bm90063a
- Batoon L, Millard SM, Raggatt LJ, Pettit AR. Osteomacs and Bone Regeneration. Curr Osteoporos Rep. 2017;15(4):385-95. doi: https://doi.org/10.1007/s11914-017-0384-x
- Lampiasi N, Russo R, Zito F. The Alternative Faces of Macrophage Generate Osteoclasts. Biomed Res Int. 2016;2016:9089610. doi: https://doi.org/10.1155/2016/9089610
- Kolk A, Handschel J, Drescher W, Rothamel D, Kloss F, Blessmann M, et al. Current trends and future perspectives of bone substitute materials - from space holders to innovative biomaterials. J Craniomaxillofac Surg. 2012;40(8):706-18. doi: https://doi.org/10.1016/j.jcms.2012.01.002
- Fernandes TJ, Hodge JM, Singh PP, Eeles DG, Collier FM, Holten I, et al. Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner. PLoS One. 2013;8(9):e73266. doi: https://doi.org/10.1371/journal.pone.0073266
- Horwood NJ. Macrophage Polarization and Bone Formation: A review. Clin Rev Allergy Immunol. 2016;51(1):79-86. doi: https://doi.org/10.1007/s12016-015-8519-2
- Ross EA, Devitt A, Johnson JR. Macrophages: The Good, the Bad, and the Gluttony. Front Immunol. 2021;12:708186. doi: https://doi.org/10.3389/fimmu.2021.708186
- Guihard P, Boutet MA, Brounais-Le Royer B, Gamblin AL, Amiaud J, Renaud A, et al. Oncostatin m, an inflammatory cytokine produced by macrophages, supports intramembranous bone healing in a mouse model of tibia injury. Am J Pathol. 2015;185(3):765-75. doi: https://doi.org/10.1016/j.ajpath.2014.11.008
- Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8(12):958-69. doi: https://doi.org/10.1038/nri2448. Erratum in: Nat Rev Immunol.2010;10(6):460.
- Vi L, Baht GS, Whetstone H, Ng A, Wei Q, Poon R, et al. Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis. J Bone Miner Res. 2015;30(6):1090-102. doi: https://doi.org/10.1002/jbmr.2422
- Anwar Z, McLeod NM, Van den Bosch P, Cairns M. A review of the use of patient reported outcome measures (PROMS) in temporomandibular joint (TMJ) surgery. J Craniomaxillofac Surg. 2024;52(2):181-7. doi: https://doi.org/10.1016/j.jcms.2023.11.005
- Ashley JW, Shi Z, Zhao H, Li X, Kesterson RA, Feng X. Genetic ablation of CD68 results in mice with increased bone and dysfunctional osteoclasts. PLoS One. 2011;6(10):e25838. doi: https://doi.org/10.1371/journal.pone.0025838
- Dowrey T, Schwager EE, Duong J, Merkuri F, Zarate YA, Fish JL. Satb2 regulates proliferation and nuclear integrity of pre-osteoblasts. Bone. 2019;127:488-98. doi: https://doi.org/10.1016/j.bone.2019.07.017
- Konermann A, Götz W, Le M, Dirk C, Lossdörfer S, Heinemann F. Histopathological Verification of Osteoimmunological Mediators in Peri-Implantitis and Correlation to Bone Loss and Implant Functional Period. J Oral Implantol. 2016;42(1):61-8. doi: https://doi.org/10.1563/aaid-joi-D-13-00355
- Schmidt-Bleek K, Schell H, Schulz N, Hoff P, Perka C, Buttgereit F, et al. Inflammatory phase of bone healing initiates the regenerative healing cascade. Cell Tissue Res. 2012;347(3):567-73. doi: https://doi.org/10.1007/s00441-011-1205-7
- Kalyan S. It May Seem Inflammatory, but Some T Cells Are Innately Healing to the Bone. J Bone Miner Res. 2016;31(11):1997-2000. doi: https://doi.org/10.1002/jbmr.2875
- Xia Z, Triffitt JT. A review on macrophage responses to biomaterials. Biomed Mater. 2006;1(1):R1-9. doi: https://doi.org/10.1088/1748-6041/1/1/R01
- Alexander KA, Chang MK, Maylin ER, Kohler T, Müller R, Wu AC, et al. Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model. J Bone Miner Res. 2011;26(7):1517-32. doi: https://doi.org/10.1002/jbmr.354
- Chang B, Ahuja N, Ma C, Liu X. Injectable scaffolds: Preparation and application in dental and craniofacial regeneration. Mater Sci Eng R Rep. 2017;111:1-26. doi: https://doi.org/10.1016/j.mser.2016.11.001
- Croissant JG, Fatieiev Y, Khashab NM. Degradability and Clearance of Silicon, Organosilica, Silsesquioxane, Silica Mixed Oxide, and Mesoporous Silica Nanoparticles. Adv Mater. 2017;29(9). doi: https://doi.org/10.1002/adma.201604634
- Chang MK, Raggatt LJ, Alexander KA, Kuliwaba JS, Fazzalari NL, Schroder K, et al. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol. 2008;181(2):1232-44. doi: https://doi.org/10.4049/jimmunol.181.2.1232
- Cho SW, Soki FN, Koh AJ, Eber MR, Entezami P, Park SI, et al. Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone. Proc Natl Acad Sci U S A. 2014;111(4):1545-50. doi: https://doi.org/10.1073/pnas.1315153111
Downloads
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 O. S. Kosinov, O. M. Mishchenko

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal. 



