Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland.
Chair and Department of Medical Microbiology, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland.
Int J Mol Sci. 2021 Jan 23;22(3):1109. 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.
慢性骨植入物免疫反应可导致愈合延迟和失败。因此，新开发的生物材料应具有高生物相容性。此外，众所周知，巨噬细胞在控制生物材料诱导的炎症反应中起着至关重要的作用。免疫细胞还合成大量信号分子，调节细胞分化和组织重塑。未激活的巨噬细胞（M0）可被激活（极化）为两种主要的巨噬细胞表型：促炎性 1 型巨噬细胞（M1）和抗炎性 2 型巨噬细胞（M2）。本研究旨在评估新开发的壳聚糖/琼脂糖/纳米羟基磷灰石骨支架（波兰专利）对巨噬细胞极化和成骨分化的影响。结果表明，在生物材料表面培养的巨噬细胞释放出高水平的抗炎细胞因子（白细胞介素-4、-10、-13、转化生长因子-β），这是 M2 表型的典型特征。此外，细胞形态评估证实了巨噬细胞在骨支架表面的 M2 极化。重要的是，在这项研究中，证明了在骨髓来源的干细胞（BMDSCs）或人成骨细胞（hFOB 1.19）存在的情况下，巨噬细胞接种生物材料的共培养增强了它们的成骨能力，证实了巨噬细胞对成骨分化过程的免疫调节作用。因此，证明了所开发的生物材料具有低炎症反应风险，并诱导巨噬细胞向具有成骨促进特性的 M2 表型极化，使其成为再生医学应用中很有前途的骨支架。
