From hurdle to springboard: The macrophage as target in biomaterial-based bone regeneration strategies

Kim, Yang‐Hee; Oreffo, R.O.C.; Dawson, Jonathan I.

doi:10.1016/j.bone.2022.116389

Cited by 19 publications

(10 citation statements)

References 184 publications

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“…37 BMP2 is also produced and regulated by macrophages, especially the M2 type. [38][39][40] Furthermore, our results showed a noticeable increase in the longitudinal migration capacity of stem cells compared to the BRT-R and β-TCP scaffolds, suggesting a continuous process of bone regeneration. Previous study showed that bredigite ceramics scaffolds facilitated the adherence and spread of osteoblasts on the surface.…”

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confidence: 51%

The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization

Xuan¹,

Li²,

Zhang³

et al. 2023

IJN

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Background: Repairing critical-sized bone defects secondary to traumatic or tumorous damage is a complex conundrum in clinical practice; in this case, artificial scaffolds exhibited preferable outcomes. Bredigite (BRT, Ca 7 MgSi 4 O 16 ) bioceramic possesses excellent physicochemical properties and biological activity as a promising candidate for bone tissue engineering. Methods: Structurally ordered BRT (BRT-O) scaffolds were fabricated by a three-dimensional (3D) printing technique, and the random BRT (BRT-R) scaffolds and clinically available β-tricalcium phosphate (β-TCP) scaffolds were compared as control groups. Their physicochemical properties were characterized, and RAW 264.7 cells, bone marrow mesenchymal stem cells (BMSCs), and rat cranial critical-sized bone defect models were utilized for evaluating macrophage polarization and bone regeneration. Results:The BRT-O scaffolds exhibited regular morphology and homogeneous porosity. In addition, the BRT-O scaffolds released higher concentrations of ionic products based on coordinated biodegradability than the β-TCP scaffolds. In vitro, the BRT-O scaffolds facilitated RWA264.7 cells polarization to pro-healing M2 macrophage phenotype, whereas the BRT-R and β-TCP scaffolds stimulated more pro-inflammatory M1-type macrophages. A conditioned medium derived from macrophages seeding on the BRT-O scaffolds notably promoted the osteogenic lineage differentiation of BMSCs in vitro. The cell migration ability of BMSCs was significantly enhanced under the BRT-O-induced immune microenvironment. Moreover, in rat cranial critical-sized bone defect models, the BRT-O scaffolds group promoted new bone formation with a higher proportion of M2-type macrophage infiltration and expression of osteogenesis-related markers. Therefore, in vivo, BRT-O scaffolds play immunomodulatory roles in promoting critical-sized bone defects by enhancing the polarization of M2 macrophages. Conclusion: 3D-printed BRT-O scaffolds can be a promising option for bone tissue engineering, at least partly through macrophage polarization and osteoimmunomodulation.

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confidence: 51%

The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization

Xuan¹,

Li²,

Zhang³

et al. 2023

IJN

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“…Majority of periostin + macrophages were M2 polarized in areas of bone formation. Both M1 and M2 macrophages were present in the process of bone repair 37 . To uncover the state of macrophage polarization during bone regeneration, we quanti ed the numbers of M1 or M2 macrophages in the bone defect site on PSD 10.…”

Section: Resultsmentioning

confidence: 99%

Periostin+ macrophages improved long bone regeneration in a mechanosensitive manner

Liu,

Wang,

Lin

et al. 2023

Preprint

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Macrophages are pivotal in the inflammatory and remodeling phases of fracture repair. Here, we investigate the effect of periostin expressed by macrophages on bone regeneration in a monocortical tibial defect (MTD) model. In this study, we show that periostin is expressed by periosteal macrophages, primarily the M2 subtype during bone regeneration. The deletion of periostin in macrophages reduces cortical bone thickness, disrupts trabecular bone connectivity, exacerbates repair impairment, and hinders M2 macrophage polarization. Mechanical stimulation has been shown to be as a regulator of periostin in macrophages. By activating transforming growth factor-β (TGF-β) and phosphorylating Smad2/3, it increases periostin expression in macrophages and induces M2 polarization. This mechanosensitive effect also reverses the delayed bone repair induced by periostin deficiency in macrophages by strengthening the angiogenesis-osteogenesis coupling. In addition, transplantation of mechanically-conditioned macrophages into the periosteum over a bone defect results in substantially enhanced repair, confirming the critical role of macrophage-secreted periostin in bone repair. In summary, our results suggest one mechanism of mechanically stimulated bone formation is the regulation of periostin expression and M2 subtype polarization in macrophages via the TGF-β/Smad2/3 signaling pathway, and demonstrates mechanically-conditioned macrophages as a promising therapeutic strategy for enhancing bone repair.

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“…M2 macrophages play an essential role in tissue inﬂammation resolution and facilitate osteogenesis, angiogenesis and bone repair through the release of anti-inﬂammatory cytokines and growth factors [ [28] , [29] , [30] ]. Since the shift of proinﬂammatory macrophages toward an anti-inﬂammatory M2 phenotype promotes bone repair, we next examined whether Hypo-sEV could induce macrophage M2 polarization in vivo .…”

Section: Resultsmentioning

confidence: 99%

Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis

Tian

Chen²,

Xiong³

et al. 2023

Bioactive Materials

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From hurdle to springboard: The macrophage as target in biomaterial-based bone regeneration strategies

Cited by 19 publications

References 184 publications

The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization

The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization

Periostin+ macrophages improved long bone regeneration in a mechanosensitive manner

Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis

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