The Chitosan/Agarose/NanoHA bone scaffold-induced M2 macrophage polarization and its effect on osteogenic differentiation in vitro
Open accessAbstract
Chronic immune response to bone implant may lead to delayed healing and its failure. Thus, newly developed biomaterials should be characterized by high biocompatibility. Moreover, it is well known that macrophages play a crucial role in the controlling of biomaterial-induced inflammatory response. Immune cells synthesize also a great amount of signaling molecules that regulate cell differentiation and tissue remodeling. Non-activated macrophages (M0) may be activated (polarized) into two main types of macrophage phenotype: proinflammatory type 1 macrophages (M1) and anti-inflammatory type 2 macrophages (M2). The aim of the present study was to assess the influence of the newly developed chitosan/agarose/nanohydroxyapatite bone scaffold (Polish Patent) on the macrophage polarization and osteogenic differentiation. Obtained results showed that macrophages cultured on the surface of the biomaterial released an elevated level of anti-inflammatory cytokines (interleukin-4, -10, -13, transforming growth factor-beta), which is typical of the M2 phenotype. Moreover, an evaluation of cell morphology confirmed M2 polarization of the macrophages on the surface of the bone scaffold. Importantly, in this study, it was demonstrated that the co-culture of macrophages-seeded biomaterial with bone marrow-derived stem cells (BMDSCs) or human osteoblasts (hFOB 1.19) enhanced their osteogenic ability, confirming the immunomodulatory effect of the macrophages on the osteogenic differentiation process. Thus, it was proved that the developed biomaterial carries a low risk of inflammatory response and induces macrophage polarization into the M2 phenotype with osteopromotive properties, which makes it a promising bone scaffold for regenerative medicine applications.
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After freeze drying, scaffolds are widely subjected to sintering to improve mechanical stability.
“Afterward, they are widely subjected to the sintering process to improve mechanical stability [84].”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [84]
Materials and Methods §3.1 describes freezing and lyophilizing this scaffold, followed by neutralization, rinsing, and air-drying. Searches for sintering and mechanical stability found no passage addressing whether scaffolds are widely sintered after freeze-drying to improve stability. (LLM, conf=0.75)
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References 37 · Cited by 51
- Authors
- Kazimierczak, P., Koziol, M., & Przekora, A.
- Affiliations
- Medical University of Lublin (PL)
- Chair and Department of Medical Microbiology, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland
- Corresponding author
- Kazimierczak, Paulina
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2021-01-23
- Volume
- 22
- Issue
- 3
- Pages
- 1109
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7866113
- OpenAlex
- W3124680705
- Cited by
- 51
- References
- 37
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 7 · 2023: 8 · 2022: 9 · 2021: 2
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Narodowe Centrum Nauki (UMO-2018/31/B/ST8/00945)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Dentistry › Oral Surgery › Dental Implant Techniques and Outcomes
- Keywords
- M2 macrophage polarization, osteogenic differentiation, anti-inflammatory cytokines, bone marrow-derived stem cells, human osteoblasts, immunomodulation, bone regeneration, biocompatibility
- MeSH terms
- Biocompatible Materials, Bone and Bones, Cell Differentiation, Humans, Macrophage Activation, Macrophages, Osteoblasts, Osteogenesis, Sepharose, Cytokines, Durapatite, Coculture Techniques, Chitosan, Nanostructures, Tissue Scaffolds, Mesenchymal Stem Cells
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