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Published in: International Orthopaedics 4/2021

01-04-2021 | Original Paper

Macrophages’ contribution to ectopic osteogenesis in combination with blood clot and bone substitute: possibility for application in bone regeneration strategies

Authors: Jelena M. Živković, Sanja T. Stojanović, Marija Đ. Vukelić-Nikolić, Milena B. Radenković, Jelena G. Najdanović, Milan Ćirić, Stevo J. Najman

Published in: International Orthopaedics | Issue 4/2021

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Abstract

Purpose

Given the great potential of macrophages in the processes of tissue repair and regeneration, the aim of our study was to examine the contribution that macrophages will have in osteogenic process when combined and implanted with blood clot (BC) and mineral bone substitute (MBS) in mice subcutaneous implantation model.

Methods

Three types of implants were constructed and implanted subcutaneously into BALB/c mice: (1) RMBM implants (made of resident tissue macrophages, BC and MBS), (2) BM implants (made of BC and MBS), and (3) M implants (made of MBS only) where the last two served as control implants. One, two, four and eight weeks after implantation implants were explanted, and histochemical, immunohistochemical, and histomorphometric analyses were performed.

Results

Increased vascularization, particularly pronounced two and four weeks after implantation and pronounced tissue infiltration in eight week term in RMBM implants compared with both other types, likewise the presence of osteoblast-like cells, osteoid-like structures, and more prominent osteopontin and osteocalcin immunoexpression in RMBM implants indicated more pronounced osteogenic process within them.

Conclusion

Our results suggest that macrophages deserve to be considered as a cell component when constructing implants in bone regenerative medicine strategies to improve bone fracture healing process.
Literature
3.
go back to reference Najdanović JG, Cvetković VJ, Stojanović S, Vukelić-Nikolić MĐ, Stanisavljević MN, Živković JM, Najman SJ (2015) The influence of adipose-derived stem cells induced into endothelial cells on ectopic vasculogenesis and osteogenesis. Cell Mol Bioeng 8:577–590. https://doi.org/10.1007/s12195-015-0403-xCrossRef Najdanović JG, Cvetković VJ, Stojanović S, Vukelić-Nikolić MĐ, Stanisavljević MN, Živković JM, Najman SJ (2015) The influence of adipose-derived stem cells induced into endothelial cells on ectopic vasculogenesis and osteogenesis. Cell Mol Bioeng 8:577–590. https://​doi.​org/​10.​1007/​s12195-015-0403-xCrossRef
8.
go back to reference Haines NM, Lack WD, Seymour RB, Bosse MJ (2016) Defining the lower limit of a “critical bone defect” in open diaphyseal tibial fractures. J Orthop Trauma 30(5):e158–e163CrossRefPubMed Haines NM, Lack WD, Seymour RB, Bosse MJ (2016) Defining the lower limit of a “critical bone defect” in open diaphyseal tibial fractures. J Orthop Trauma 30(5):e158–e163CrossRefPubMed
10.
go back to reference Vukicevic S, Oppermann H, Verbanac D, Jankolija M, Popek I, Curak J, Brkljacic J, Pauk M, Erjavec I, Francetic I, Dumic-Cule I, Jelic M, Durdevic D, Vlahovic T, Novak R, Kufner V, Bordukalo Niksic T, Kozlovic M, Banic Tomisic Z, Bubic-Spoljar J, Bastalic I, Vikic-Topic S, Peric M, Pecina M, Grgurevic L (2014) The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing. Int Orthop 38(3):635–647. https://doi.org/10.1007/s00264-013-2201-1CrossRefPubMed Vukicevic S, Oppermann H, Verbanac D, Jankolija M, Popek I, Curak J, Brkljacic J, Pauk M, Erjavec I, Francetic I, Dumic-Cule I, Jelic M, Durdevic D, Vlahovic T, Novak R, Kufner V, Bordukalo Niksic T, Kozlovic M, Banic Tomisic Z, Bubic-Spoljar J, Bastalic I, Vikic-Topic S, Peric M, Pecina M, Grgurevic L (2014) The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing. Int Orthop 38(3):635–647. https://​doi.​org/​10.​1007/​s00264-013-2201-1CrossRefPubMed
13.
go back to reference Hoemann CD, Hurtig M, Rossomacha E, Sun J, Chevrier A, Shive MS, Buschmann MD (2005) Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. J Bone Joint Surg Am 87(12):2671–2686CrossRefPubMed Hoemann CD, Hurtig M, Rossomacha E, Sun J, Chevrier A, Shive MS, Buschmann MD (2005) Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. J Bone Joint Surg Am 87(12):2671–2686CrossRefPubMed
15.
16.
go back to reference Najman SJ, Cvetković VJ, Najdanović JG, Stojanović S, Vukelić-Nikolić MĐ, Vučković I, Petrović D (2016) Ectopic osteogenic capacity of freshly isolated adipose-derived stromal vascular fraction cells supported with platelet-rich plasma: a simulation of intraoperative procedure. J Craniomaxillofac Surg 44(10):1750–1760. https://doi.org/10.1016/j.jcms.2016.08.011CrossRefPubMed Najman SJ, Cvetković VJ, Najdanović JG, Stojanović S, Vukelić-Nikolić MĐ, Vučković I, Petrović D (2016) Ectopic osteogenic capacity of freshly isolated adipose-derived stromal vascular fraction cells supported with platelet-rich plasma: a simulation of intraoperative procedure. J Craniomaxillofac Surg 44(10):1750–1760. https://​doi.​org/​10.​1016/​j.​jcms.​2016.​08.​011CrossRefPubMed
26.
go back to reference Yu B, Zhang Y, Li X, Wang Q, Ouyang Y, Xia Y, Yu B, Lin B, Li S, Fan Y, Chen Y (2013) The use of injectable chitosan/nanohydroxyapatite/collagen composites with bone marrow mesenchymal stem cells to promote ectopic bone formation in vivo. J Nanomater 2013:506593. https://doi.org/10.1155/2013/506593CrossRef Yu B, Zhang Y, Li X, Wang Q, Ouyang Y, Xia Y, Yu B, Lin B, Li S, Fan Y, Chen Y (2013) The use of injectable chitosan/nanohydroxyapatite/collagen composites with bone marrow mesenchymal stem cells to promote ectopic bone formation in vivo. J Nanomater 2013:506593. https://​doi.​org/​10.​1155/​2013/​506593CrossRef
Metadata
Title
Macrophages’ contribution to ectopic osteogenesis in combination with blood clot and bone substitute: possibility for application in bone regeneration strategies
Authors
Jelena M. Živković
Sanja T. Stojanović
Marija Đ. Vukelić-Nikolić
Milena B. Radenković
Jelena G. Najdanović
Milan Ćirić
Stevo J. Najman
Publication date
01-04-2021
Publisher
Springer Berlin Heidelberg
Published in
International Orthopaedics / Issue 4/2021
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-020-04826-0

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