THE ROLE OF MACROPHAGES IN BONE TISSUE REGENERATION: MECHANISMS, SPECIFICS OF THE OSTEOIMMUNE RESPONSE TO METALLIC IMPLANTS, AND PROSPECTS OF BIOENGINEERING

DOI: 10.22138/2500-0918-2026-23-2-289-305

A.A. Markov¹, G.S. Solovev¹, V.A. Chereshnev²

¹Tyumen State Medical University, Ministry of Health of Russia, Tyumen, Russian Federation
²Research Institute of Immunology and Physiology, Russian Academy of Sciences, Ural Branch, Ekaterinburg, Russian Federation

Abstract. This review summarizes current data on the cellular and molecular mechanisms of macrophage participation in bone tissue regeneration. The features of the macrophage response during the implantation of metal structures are considered, and the translational potential of immunomodulatory biomaterials for optimizing osteosynthesis outcomes is evaluated. It is shown that macrophages are the central cellular integrators of the osteoimmune microenvironment, coordinating the inflammatory, angiogenic, and osteogenic phases of repair. Effective activation of osteoregeneration in response to trauma (mechanical damage) requires the establishment of a strictly time-ordered crosstalk between macrophages and neutrophils, Treg lymphocytes, and mesenchymal stromal cells. The initiation of a foreign body reaction during the implantation of metal structures shifts the balance towards persistent inflammation and RANKL-mediated osteoclastogenesis. The development of osteoimmunomodulatory biomaterials and bioactive coatings that program the macrophage phenotype in situ opens up fundamentally new possibilities in the treatment of patients with bone pathology, primarily in traumatology and orthopedics.

Keywords: macrophages, bone tissue regeneration, osteoimmunology, foreign body reaction, metallic implants, biomaterials, osteosynthesis, macrophage polarization

There is no conflict of interest
Contact information of the corresponding author:
Markov Alexander Anatolyevich
alexdoktor@inbox.ru
Received: 20.05.2026

For citation: Markov A.A., Solovev G.S., Chereshnev V.A. The role of macrophages in bone tissue regeneration: mechanisms, specifics of the osteoimmune response to metallic implants, and prospects of bioengineering [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2026, Vol. 23, no. 2, pp. 289–305. DOI: 10.22138/2500-0918-2026-23-2-289-305 (In Russ)

Financing. The research was carried out within the state assignment of Ministry of Health of the Russian Federation (AMRU-2025-0005).

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Authors
Markov Aleksandr A.
PhD (Medicine), Director of the University Research Institute of Medical Biotechnology and Biomedicine
Tyumen State Medical University, Ministry of Health of Russia
625023, Tyumen, Odesskaya st., 54, Russia
alexdoktor@inbox.ru
https://orcid.org/0000-0001-7471-4792

Solovev Georgii S.
Doctor of Medical Sciences, Professor of histology and embryology department named after P.V. Dunaeva of the Tyumen State Medical University
solovyev@tyumsmu.ru
https://orcid.org/0000-0003-4553-0569

Chereshnev Valery A.
Doctor of Medical Sciences, Academician of the Russian Academy of Sciences, Scientific Advisor, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Ekaterinburg, Russia
v.chereshnev@mail.ru
https://orcid.org/0000-0003-4329-147X