Biodegradable magnesium combined with distraction osteogenesis synergistically stimulates bone tissue regeneration via CGRP-FAK-VEGF signaling axis

Li, Ye; Xu, Jiankun; Mi, Jie; He, Xuan; Pan, Qi; Zheng, Lizhen; Zu, Haiyue; Chen, Ziyi; Dai, Bingyang; Li, Xu; Pang, Qi; Zou, Li; Zhou, Liangbin; Huang, Le; Tong, Wenxue; Li, Gang; Qin, Ling

doi:10.1016/j.biomaterials.2021.120984

Cited by 85 publications

(64 citation statements)

References 76 publications

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“…Tissue engineering uses exogenous or endogenous growth factors, seed cells and scaffolds to simulate these healing processes. Many studies have described the effects of single factor and multi factor applications on bone healing ( Hamushan et al, 2020 ; Shen et al, 2021 ; Ye et al, 2021 ; Han et al, 2022 ). Our study showed that injecting rrPDGF-BB into the distraction space during the mineralization period of distraction osteogenesis could promote the formation of new bone in the distraction area and promote healing.…”

Section: Discussionmentioning

confidence: 99%

“…Some scholars believe that the principle of poor bone regeneration is that there is a problem in the aggregation and proliferation of original osteoblasts, or there is a problem in the differentiation of original osteoblasts ( Feng et al, 2016 ). Clinical studies have found that patients with primary osteoblast deficiency, severe trauma and severe tissue defects after radiotherapy will suffer from bone regeneration deficiency ( Hamushan et al, 2020 ; Shen et al, 2021 ; Ye et al, 2021 ). Therefore, when using distraction osteogenesis to treat large bone defects, it may be a reasonable treatment plan to supplement exogenous original osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

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Rat bone marrow mesenchymal stem cells induced by rrPDGF-BB promotes bone regeneration during distraction osteogenesis

Zhang²,

Zhang³

et al. 2023

Front. Bioeng. Biotechnol.

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Background: In the clinical treatment of large bone defects, distraction osteogenesis can be used. However, some patients may suffer from poor bone regeneration, or even delayed healing or non-union. Problems with the aggregation and proliferation of primary osteoblasts, or problems with the differentiation of primary osteoblasts will lead to poor bone regeneration. Therefore, supplementing exogenous primary osteoblasts and growth factors when using distraction osteogenesis may be a treatment plan with great potential.Methods: Bone marrow mesenchymal stem cells (BMSCs) were extracted from rats and cultured. Subsequently, Recombinant Rat Platelet-derived Growth Factor BB (rrPDGF-BB) was used to induce bone marrow mesenchymal stem cells. At the same time, male adult rats were selected to make the right femoral distraction osteogenesis model. During the mineralization period, phosphate buffer salt solution (control group), non-induction bone marrow mesenchymal stem cells (group 1) and recombinant rat platelet-derived growth factor BB intervened bone marrow mesenchymal stem cells (group 2) were injected into the distraction areas of each group. Then, the experimental results were evaluated with imaging and histology. Statistical analysis of the data showed that the difference was statistically significant if p < 0.05.Results: After intervention with recombinant rat platelet-derived growth factor BB on bone marrow mesenchymal stem cells, the cell morphology changed into a thin strip. After the cells were injected in the mineralization period, the samples showed that the callus in group 2 had greater hardness and the color close to the normal bone tissue; X-ray examination showed that there were more new callus in the distraction space of group 2; Micro-CT examination showed that there were more new bone tissues in group 2; Micro-CT data at week eight showed that the tissue volume, bone volume, percent bone volume, bone trabecular thickness, bone trabecular number and bone mineral density in group 2 were the largest, and the bone trabecular separation in group 2 was the smallest. There was a statistical difference between the groups (p < 0.05); HE staining confirmed that group 2 formed more blood vessels and chondrocytes earlier than the control group. At 8 weeks, the bone marrow cavity of group 2 was obvious, and some of them had been fused.Conclusion: The study confirmed that injecting bone marrow mesenchymal stem cellsBB into the distraction space of rats can promote the formation of new bone in the distraction area and promote the healing of distraction osteogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rat bone marrow mesenchymal stem cells induced by rrPDGF-BB promotes bone regeneration during distraction osteogenesis

Zhang²,

Zhang³

et al. 2023

Front. Bioeng. Biotechnol.

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“…It has been demonstrated that magnesium ion release implantation enhances the synthesis of CGRP in the dorsal root ganglion (DRG) and its release at the end of the sensory nerve periosteum, and the CGRP mediated pathway has been identified as a major mechanism of potential magnesium to promote bone formation in fracture healing. Some study also demonstrates that CGRP processes an equal effect on migration and tube formation compared with VEGF, accompanied by increased VEGF expression, and activation of focal adhesion kinase (FAK), thereby acting as a strong proangiogenic growth factor during bone healing ( Sun et al, 2020 ; Ye Li et al, 2021 ). Zhang et al (2022) demonstrated through in vitro and in vivo studies that the promotion of bone formation by Mg is largely mediated by CGRP released from the sensory neuron terminals of the periosteum of the long bone axis, CGRP mediated periosteal nerves, and periosteal stem cells.…”

Section: Mechanisms Of Osteogenesis Of Mg Matrix Compositesmentioning

confidence: 99%

Regulation of Magnesium Matrix Composites Materials on Bone Immune Microenvironment and Osteogenic Mechanism

Nie

Zhang

Lei

et al. 2022

Front. Bioeng. Biotechnol.

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Despite magnesium based metal materials are widely used in bone defect repair, there are still various deficiencies, and their properties need to be optimized. Composites synthesized with magnesium based metal as matrix are the research hotspot, and the host immune response after biomaterial implantation is very important for bone binding. By studying the immunoregulation of bone biomaterials, it can regulate the immune response in the process of osteogenesis and create a good local immune microenvironment, which is conducive to biomaterials to reduce inflammatory response and promote good bone binding. This article introduces the osteogenic mechanism of magnesium based metal materials and its regulation on bone immune microenvironment in detail.

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“…When postoperative biophysical stimuli loading strategies are used in combination of other pillars of bone tissue engineering, their clinical complications or drawbacks may diminish. For example, DO is a long-term treatment that may cause infections or delay, but it shows great promise for bone regeneration when combined with osteoinducive Mg nail, which could reduce the treatment time of traditional DO ( Ye et al, 2021 ).…”

Section: Applications Of Biophysical Stimuli For Bone Tissue Engineeringmentioning

confidence: 99%

Biophysical Stimuli as the Fourth Pillar of Bone Tissue Engineering

Hao

Wang

et al. 2021

Front. Cell Dev. Biol.

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The repair of critical bone defects remains challenging worldwide. Three canonical pillars (biomaterial scaffolds, bioactive molecules, and stem cells) of bone tissue engineering have been widely used for bone regeneration in separate or combined strategies, but the delivery of bioactive molecules has several obvious drawbacks. Biophysical stimuli have great potential to become the fourth pillar of bone tissue engineering, which can be categorized into three groups depending on their physical properties: internal structural stimuli, external mechanical stimuli, and electromagnetic stimuli. In this review, distinctive biophysical stimuli coupled with their osteoinductive windows or parameters are initially presented to induce the osteogenesis of mesenchymal stem cells (MSCs). Then, osteoinductive mechanisms of biophysical transduction (a combination of mechanotransduction and electrocoupling) are reviewed to direct the osteogenic differentiation of MSCs. These mechanisms include biophysical sensing, transmission, and regulation. Furthermore, distinctive application strategies of biophysical stimuli are presented for bone tissue engineering, including predesigned biomaterials, tissue-engineered bone grafts, and postoperative biophysical stimuli loading strategies. Finally, ongoing challenges and future perspectives are discussed.

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Biodegradable magnesium combined with distraction osteogenesis synergistically stimulates bone tissue regeneration via CGRP-FAK-VEGF signaling axis

Cited by 85 publications

References 76 publications

Rat bone marrow mesenchymal stem cells induced by rrPDGF-BB promotes bone regeneration during distraction osteogenesis

Rat bone marrow mesenchymal stem cells induced by rrPDGF-BB promotes bone regeneration during distraction osteogenesis

Regulation of Magnesium Matrix Composites Materials on Bone Immune Microenvironment and Osteogenic Mechanism

Biophysical Stimuli as the Fourth Pillar of Bone Tissue Engineering

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