A sequential macrophage activation strategy for bone regeneration: A micro/nano strontium-releasing composite scaffold loaded with lipopolysaccharide

• DOI: 10.1016/j.mtbio.2024.101063
• Publication Date: 2024-04-21T05:20:54Z
• Authors: Jinhui Huang; Jiawei Wei; Xue Xia; Shiqi Xiao; Shue Jin; Qin Zou; Yi Zuo; Yubao Li; Jidong Li
• Keywords: 0301 basic medicine; Degradation; Medicine (General); 03 medical and health sciences; R5-920; QH301-705.5; Full Length Article; Biology (General); Micro/nano composite; Macrophage phenotype regulation; Bone regeneration

Effective tissue repair relies on the orchestration of different macrophage phenotypes, both the M2 phenotype (promotes tissue repair) and M1 phenotype (pro-inflammatory) deserve attention. In this study, we propose a sequential immune activation strategy to mediate bone regeneration, by loading lipopolysaccharide (LPS) onto the surface of a strontium (Sr) ions -contained composite scaffold, which was fabricated by combining Sr-doped micro/nano-hydroxyapatite (HA) and dual degradable matrices of polycaprolactone (PCL) and poly (lactic-co-glycolic acid) (PLGA). Our strategy involves the sequential release of LPS to promote macrophage homing and induce the expression of the pro-inflammatory M1 phenotype, followed by the release of Sr ions to suppress inflammation. In vitro and in vivo experiments demonstrated that, the appropriate pro-inflammatory effects at the initial stage of implantation, along with the anti-inflammatory effects at the later stage, as well as the structural stability of the scaffolds conferred by the composition, can synergistically promote the regeneration and repair of bone defects.