Electrospun naringin-loaded microsphere/sucrose acetate isobutyrate system promotes macrophage polarization toward M2 and facilitates osteoporotic bone defect repair

Abstract

Repairing osteoporotic bone defects is still a major clinical challenge. Recent studies have revealed that immune response is also essential in osteogenesis. The intrinsic inflammatory response of the host, especially the M1/M2 polarization status and inflammatory secretory function of macrophages, can directly affect the osteogenic differentiation. Therefore, in this study, an electrospun naringin-loaded microspheres/sucrose acetate isobutyrate (Ng-m-SAIB) system was constructed to investigate its effect on the polarization of macrophage and osteoporotic bone defects. The results of both in vitro and in vivo experiments showed that Ng-m-SAIB had good biocompatibility and could promote the polarization of macrophage toward M2, thereby forming a favourable microenvironment for osteogenesis. The animal experiments also showed that Ng-m-SAIB could promote the osteogenesis of critical size defects in the skull of osteoporotic model mouse (the senescence-accelerated mouse-strain P6, SAMP6). Together, these results collectively suggested that Ng-m-SAIB might be a promising biomaterial to treat osteoporotic bone defects with favourable osteo-immunomodulatory effects.

Direct osteogenesis and immunomodulation dual function via sustained release of naringin from the polymer scaffold

“…In addition, it was reported that the anti-inflammatory effects of NG are regulated by multiple mechanisms including (1) the promotion of macrophage M2 polarization through PI3K/AKT/mTOR signaling pathways; (2) inhibition of multiple inflammation-related signaling pathways (such as NF-κB and MAPK pathways) to reduce the production of inflammation-related factors, thereby suppressing inflammation, and (3) adjustment of the peroxisome proliferator-activated receptor (PPAR)/miR-21 pathway participating in the regulation of inflammation. 46–49…”

“…In addition, it was reported that the anti-inflammatory effects of NG are regulated by multiple mechanisms including (1) the promotion of macrophage M2 polarization through PI3K/AKT/ mTOR signaling pathways; (2) inhibition of multiple inflammation-related signaling pathways (such as NF-kB and MAPK pathways) to reduce the production of inflammation-related factors, thereby suppressing inflammation, and (3) adjustment of the peroxisome proliferator-activated receptor (PPAR)/miR-21 pathway participating in the regulation of inflammation. [46][47][48][49] Bone regeneration involves three successive phases in the induction of new bone regeneration: inflammation, repair, and remodeling phases. As shown in earlier research, prolonged chronic inflammation caused by macrophages of M1 type could induce the absorption of bone tissue, which causes the formation of a fibrous envelope, blocks the combination of bone cells and implants, and ultimately leads to the failure of bone repair.…”

Fibrous topology promoted pBMP2-activated matrix on titanium implants boost osseointegration

“…Next, the marker genes related to osteogenesis differentiation were detected by Q-PCR analysis in BMSCs cultured on pBMP2 incorporated DAM-coated Ti surface for 3, 7 and 14 days ( Figure 3E ). ALP is an important marker during early osteogenic differentiation [ 49 ], of which peak expressions generally appeared at 7 days. BMSCs cultured on FG Ti-P/pBMP2-6 showed a 1.3 and 1.9-fold enhanced expression of ALP compared to CG Ti-P/pBMP2-6 and uncoated FG Ti, respectively.…”

Sustained Release of Dexamethasone from 3D-Printed Scaffolds Modulates Macrophage Activation and Enhances Osteogenic Differentiation

“…We first identified SAIB as an effective excipient among the five compounds (Pluronic F127, Pluronic F68, Pluronic L31, and Span80) that were tested. SAIB has been used as a viscous injectable depot system for sustained drug release and elicited mild inflammation after intramuscular injection in rats. , However, its effectiveness as an excipient in PCL to sustain drug release has not been tested before. These five excipients all have shown surfactant properties and exhibited a wide range of hydrophilicity/hydrophobicity.…”