The Chitosan/Agarose/NanoHA Bone Scaffold-Induced M2 Macrophage Polarization and Its Effect on Osteogenic Differentiation In Vitro

• Published in: International journal of molecular sciences Vol. 22; no. 3; p. 1109
• Main Authors: Kazimierczak, Paulina, Koziol, Malgorzata, Przekora, Agata
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.01.2021; MDPI
• Subjects: Biocompatibility; biomaterial; Biomedical materials; Bone biomaterials; Bone healing; Bone marrow; bone regeneration; Cell adhesion & migration; Cell culture; Cell differentiation; Chitosan; co-culture; Cytokines; Cytology; Differentiation (biology); Fibroblasts; Genotype & phenotype; Growth factors; Immune response; Immune system; Immunomodulation; Inflammation; Inflammatory response; Interleukin 4; Macrophages; mesenchymal stem cells; Nitric oxide; Osteoblasts; osteogenic differentiation; Phenotypes; Polarization; Regenerative medicine; Scaffolds; Stem cells; Surgical implants; Tissue engineering; Transforming growth factor-b; Tumor necrosis factor-TNF; biomaterial; mesenchymal stem cells; osteogenic differentiation; bone regeneration; cytokines; osteoblasts; co-culture
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22031109

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.