Serial cellular events in bone formation initiated by calcium phosphate ceramics

Guo, Xiaodong; Li, Mingzheng; Qi, Wei; Bai, Hetian; Nie, Zhangling; Hu, Zhiqiao; Xiao, Yu; Bruijn, Joost D. de; Bao, Chongyun; Yuan, Huipin

doi:10.1016/j.actbio.2021.07.037

Cited by 21 publications

(24 citation statements)

References 57 publications

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“…13 Finally, our previous work identified that osteoclasts could be detected at the very beginning of the material-instructed ectopic bone formation process (almost 1 week after implantation) and may serve as a powerful regulator to accelerate material absorption. 20 Similarly, osteoclasts can also be found in the early stages of endochondral osteogenesis to adsorb the mature cartilage scaffold. In our hypothesis, osteo-inductive scaffolds may serve as cartilage in endochondral osteogenesis by providing Ca and P ions, serial cytokines, and essential space to promote osteogenesis during osteoclast absorption.…”

Section: Discussionmentioning

confidence: 99%

“…Detailed methods of preparation were presented in former studies. 19,20,40 2.2.2 Surgery. The TCPs and TCPb were implanted subscutaneously and bilaterally into mice's back.…”

Section: Materials and Their Characterizationmentioning

confidence: 99%

“…These events should be appropriately tuned in a proper manner to obtain better osteogenesis results. 19,20 However, osteo-inductive materials still face difficulties in meeting clinical demands mainly because some paradoxical phenomena remain in material-induced osteo-induction and the related mechanisms also need to be explained. For example, at the early stage of implantation, local original blood vessels are severely impaired by surgery, but new vessels have not yet formed.…”

Section: Introductionmentioning

confidence: 99%

“…These events should be appropriately tuned in a proper manner to obtain better osteogenesis results. 19,20…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia inducible factor-1 signaling pathway in macrophage involved angiogenesis in materials-instructed osteo-induction

et al. 2022

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Section: Discussionmentioning

confidence: 99%

“…Detailed methods of preparation were presented in former studies. 19,20,40 2.2.2 Surgery. The TCPs and TCPb were implanted subscutaneously and bilaterally into mice's back.…”

Section: Materials and Their Characterizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…These events should be appropriately tuned in a proper manner to obtain better osteogenesis results. 19,20…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia inducible factor-1 signaling pathway in macrophage involved angiogenesis in materials-instructed osteo-induction

et al. 2022

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“…Calcium phosphate ceramics received a great deal of interest, especially for the hard tissue repair and regeneration applications due to their biocompatibility, osteo-conductivity, and biodegradability [ 23 ]. In this study, we prepared BCP as previously described [ 24 ] and used a model of intramuscular implantation in mice to confirm the osteo-inductive capability of BCP. Intramuscular implantation was simple and widely used, which allow for relatively controlled bone formation in in vivo experiment.…”

Section: Discussionmentioning

confidence: 99%

Fibroblasts Mediate Ectopic Bone Formation of Calcium Phosphate Ceramics

Zhao

et al. 2022

Materials

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Heterogeneity of fibroblasts directly affects the outcome of tissue regeneration; however, whether bioactive ceramics regulate bone regeneration through fibroblasts is unclear. Ectopic bone formation model with biphasic calcium phosphate (BCP) implantation was used to investigate the temporal and spatial distribution of fibroblasts around ceramics. The effect of BCP on L929 fibroblasts was evaluated by EdU assay, transwell assay, and qRT-PCR. Further, the effect of its conditioned medium on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was confirmed by ALP staining. SEM and XRD results showed that BCP contained abundant micro- and macro-pores and consisted of hydrogen-apatite (HA) and β-tricalcium phosphate (β-TCP) phases. Subsequently, BCP implanted into mice muscle successfully induced osteoblasts and bone formation. Fibroblasts labelled by vimentin gathered around BCP at 7 days and peaked at 14 days post implantation. In vitro, BCP inhibited proliferation of L929 fibroblast but promoted its migration. Moreover, expression of Col1a1, Bmp2, and Igf1 in L929 treated by BCP increased significantly while expression of Tgfb1 and Acta did not change. ALP staining further showed conditioned media from L929 fibroblasts treated by BCP could enhance osteogenic differentiation of BMSCs. In conclusion, fibroblasts mediate ectopic bone formation of calcium phosphate ceramics.

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Hypoxia Drives Material‐Induced Heterotopic Bone Formation by Enhancing Osteoclastogenesis via M2/Lipid‐Loaded Macrophage Axis

Jiang

et al. 2023

Advanced Science

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Heterotopic ossification (HO) is a double‐edged sword. Pathological HO presents as an undesired clinical complication, whereas controlled heterotopic bone formation by synthetic osteoinductive materials shows promising therapeutic potentials for bone regeneration. However, the mechanism of material‐induced heterotopic bone formation remains largely unknown. Early acquired HO being usually accompanied by severe tissue hypoxia prompts the hypothesis that hypoxia caused by the implantation coordinates serial cellular events and ultimately induces heterotopic bone formation in osteoinductive materials. The data presented herein shows a link between hypoxia, macrophage polarization to M2, osteoclastogenesis, and material‐induced bone formation. Hypoxia inducible factor‐1α (HIF‐1α), a crucial mediator of cellular responses to hypoxia, is highly expressed in an osteoinductive calcium phosphate ceramic (CaP) during the early phase of implantation, while pharmacological inhibition of HIF‐1α significantly inhibits M2 macrophage, subsequent osteoclast, and material‐induced bone formation. Similarly, in vitro, hypoxia enhances M2 macrophage and osteoclast formation. Osteoclast‐conditioned medium enhances osteogenic differentiation of mesenchymal stem cells, such enhancement disappears with the presence of HIF‐1α inhibitor. Furthermore, metabolomics analysis reveals that hypoxia enhances osteoclastogenesis via the axis of M2/lipid‐loaded macrophages. The current findings shed new light on the mechanism of HO and favor the design of more potent osteoinductive materials for bone regeneration.

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Serial cellular events in bone formation initiated by calcium phosphate ceramics

Cited by 21 publications

References 57 publications

Hypoxia inducible factor-1 signaling pathway in macrophage involved angiogenesis in materials-instructed osteo-induction

Hypoxia inducible factor-1 signaling pathway in macrophage involved angiogenesis in materials-instructed osteo-induction

Fibroblasts Mediate Ectopic Bone Formation of Calcium Phosphate Ceramics

Hypoxia Drives Material‐Induced Heterotopic Bone Formation by Enhancing Osteoclastogenesis via M2/Lipid‐Loaded Macrophage Axis

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