Macrophages activated by akermanite/alginate composite hydrogel stimulate migration of bone marrow-derived mesenchymal stem cells

• Published in: Biomedical materials (Bristol) Vol. 16; no. 4
• Main Authors: Zhu, Yanlun, Deng, Shuai, Ma, Zhijie, Kong, Lingzhi, Li, Haiyan, Chan, Hon Fai
• Format: Journal Article
• Language: English
• Published: England 01-07-2021
• Subjects: Alginates; Animals; Bone Marrow; Cell Differentiation; Ceramics; Hydrogels; Macrophages; Mesenchymal Stem Cells - metabolism; Osteogenesis; Rats; akermanite; macrophage; biomaterial; bone marrow-derived mesenchymal stem cells; immune environment
• ISSN: 1748-605X
• DOI: 10.1088/1748-605X/abe80a

Akermanite (Aker) has been widely used for bone regeneration through regulating osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). Previously, we developed an injectable Aker/sodium alginate (Aker/SA) hydrogel to facilitate bone regeneration. However, the effect of this injectable hydrogel on the
response, particularly the inflammatory response, has not been fully understood. Here, to elucidate the response following the implantable of Aker/SA hydrogel, we investigated the interaction among Aker/SA hydrogel, inflammatory cells and cells involved in bone regeneration (BMSCs). Specifically, we cultured macrophages (RAW 264.7 cell line) with the extract liquid of Aker/SA and assessed their phenotypic changes. Subsequently, BMSCs (2 × 10
cells per 24 well) were cultured with different conditioned media including that of Aker/SA hydrogel-activated macrophages to investigate their effect on cell migration. Finally, Aker/SA hydrogel was injected subcutaneously (1 × 10
cells ml
) in rat to verify its effect
. The
results indicated that Aker/SA hydrogel activated macrophages towards M2 phenotype and stimulated macrophages to express anti-inflammatory factors. In addition, the conditioned medium collected from Aker-activated macrophages could accelerate the migration of BMSCs in 24 h. Consistent with the
results, when the Aker/SA hydrogel was injected subcutaneously, more M2 macrophages could be observed than when the SA solution was injected after 7 d. Besides, when BMSCs were delivered via subcutaneous injection, more BMSCs were recruited by the Aker/SA hydrogel than the SA solution. All these results suggest that the Aker/SA hydrogel can modulate the immune environment at the implantation site and subsequently recruit BMSCs, which can be one of the mechanisms through which the Aker/SA hydrogel accelerates new bone formation.