VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo

Wernike, E.; Montjovent, Marc-Oliver; Liu, Y.; Wismeijer, Daniël; Hunziker, Ernst B.; Siebenrock, Klaus A.; Hofstetter, W.; Klenke, Frank M.

doi:10.22203/ecm.v019a04

Cited by 160 publications

(27 citation statements)

References 45 publications

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“…Among other processes, angiogenesis occupies a central role in the whole process of bone regeneration after fracture[18–19]. VEGF is the most important factor with a significant role in both vasculogenesis (vasculature formation de novo) and angiogenesis (vessel formation from existing vasculature), but currently, only a limited number of studies have utilized VEGF for regeneration of bone defects in vivo[20]. Our study showed that femur-stabilized bone fractures generated in healthy mice were efficiently repaired following injection of PTH 1-34 or/and MSCs via promoting angiogenesis and osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

PTH1-34 improves bone healing by promoting angiogenesis and facilitating MSCs migration and differentiation in a stabilized fracture mouse model

Jiang

Shi

et al. 2019

PLoS ONE

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ObjectivePTH1-34 (parathyroid hormone 1–34) is the only clinical drug to promote osteogenesis. MSCs (mesenchymal stem cells) have multidirectional differentiation potential and are closely related to fracture healing. This study was to explore the effects of PTH1-34 on proliferation and differentiation of endothelial cells and MSCs in vitro, and on angiogenesis, and MSCs migration during fracture healing in vivo.MethodsMice with stabilized fracture were assigned to 4 groups: CON, PTH (PTH1-34 40 μg/kg/day), MSC (transplanted with 105 MSCs), PTH+MSCs. Mice were sacrificed 14 days after fracture, and callus tissues were harvested for microCT scan and immunohistochemistry analysis. The effects of PTH1-34 on angiogenesis, and MSCs differentiation and migration were assessed by wound healing, tube formation and immunofluorescence staining.ResultsTreatment with either PTH1-34, or MSCs promoted bone healing and vascular formation in fracture callus. The callus bone mass, bone volume, and bone mineral density were all greater in PTH and/or MSC groups than they were in CON (p<0.05). PTH1-34 increased small vessels formation (diameter ≤50μm), whereas MSCs increased the large ones (diameter >50μm). Expression of CD31 within calluses and trabecular bones were significantly higher in PTH1-34 treated group than that of not (p<0.05). Expression of CD31, VEGFR, VEGFR2, and vWF was upregulated, and wound healing and tube formation were increased in MSCs treated with PTH1-34 compared to that of control.ConclusionsPTH1-34 improved the proliferation and differentiation of endothelial cells and MSCs, enhancing migration of MSCs to bone callus to promote angiogenesis and osteogenesis, and facilitating fracture healing.

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Section: Discussionmentioning

confidence: 99%

PTH1-34 improves bone healing by promoting angiogenesis and facilitating MSCs migration and differentiation in a stabilized fracture mouse model

Jiang

Shi

et al. 2019

PLoS ONE

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“…Several chemo-and cytokines expressed by macrophages and also MNGCs are responsible for the regulation of the cellular response and to the formation of new bone [4,. For example, cytokines such as interleukin 10 or 12 (IL-10 or IL-12) or the vascular endothelial growth factor (VEGF) inhibit osteoclast formation and induce the differentiation of osteoblasts or enhance vascularization and stimulation of osteoblast recruitment [23,29,30,[36][37][38][39][40][41][42]. On the other hand, proinflammatory cytokines such as the chemokine (C-C motif) ligand 5 (CCL5), which is also known as RANTES (regulated on activation, normal T cell expressed and secreted), are associated with promotion of the bone repair process by recruitment of monocytes and macrophages have been shown to promote angiogenesis [35].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Biomaterial-Induced Secretome: Physical Bone Substitute Characteristics Influence the Cytokine Expression of Macrophages

Barbeck

Schröder

Alkildani³

et al. 2021

IJMS

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In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo.

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“…To optimize its osteoinductive efficacy, BMP-2 needs to be delivered to target sites at a sustained and low level (Hunziker, Enggist, Küffer, Buser, & Liu, 2012;Liu, Hunziker, Randall, de Groot, & Layrolle, 2003). Our biomimetic calcium phosphate coating has been proven as an effective tool for delivering growth factors slowly and steadily (Liu et al, 2007;Wernike et al, 2010). In the present study, the inc.…”

Section: Discussionmentioning

confidence: 95%

Vertical bone augmentation with simultaneous implantation using deproteinized bovine bone block functionalized with a slow delivery of BMP‐2

Teng

Wei

et al. 2020

Clinical Oral Implants Res

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Objective We hypothesized that a biomimetic calcium phosphate (CaP) coating which incorporates morphogenetic protein 2 (BMP‐2) on the deproteinized bovine bone (DBB) blocks could be used to enhance the vertical alveolar ridge augmentation for the one‐stage onlay surgery with simultaneous implants insertion. We aimed to test this hypothesis in vivo. Material and methods Beagles dogs were used for the study (n = 6 specimens per group). One month after building the edentulous animal model, 4 mm vertical alveolar bone loss were surgically created and four groups of blocks (W × L × H: 7 mm × 10 mm × 4 mm) were randomly fixed onto the reduced alveolar ridge by implants: (a) DBB blocks alone (negative control group); (b) DBB blocks with superficial adsorption of 50 μg BMP‐2 (ad.BMP‐2 group); (c) DBB blocks coated by biomimetic CaP coating which incorporates 50 μg BMP‐2 (inc.BMP‐2 group); and (d) autologous bone blocks (positive control group). After 3 months of healing, samples were harvested for micro‐CT and histomorphometric analyses. Results In histomorphometry, the inc.BMP‐2 group showed a significantly thicker (coronal‐apically) and wider (buccal‐lingually) augmented bone area, better bone‐to‐implant contact than the negative control group. In both the micro‐CT and histomorphometry, the inc.BMP‐2 group showed more mineralized tissue than the negative control group and the inc.BMP‐2 group also showed significantly more newly formed bone and residual grafts than the negative control group in the upper half of the blocks. In micro‐CT, the inc.BMP‐2 group showed significantly more bone‐to‐graft contact percentage than the ad.BMP‐2 group. In both micro‐CT and histomorphometry, the inc.BMP‐2 group showed significantly more percentage of mineralized tissue than the ad.BMP‐2 group. No significant differences were found between the inc.BMP‐2 group and the positive control group either in micro‐CT or in histomorphometry. Conclusions The DBB blocks with coating‐delivered BMP‐2 significantly enhanced the efficacy of vertical alveolar bone augmentation, compared with the unloaded blocks and blocks with adsorbed BMP‐2, in the one‐stage onlay surgery with simultaneous implant insertion.

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VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo

Cited by 160 publications

References 45 publications

PTH1-34 improves bone healing by promoting angiogenesis and facilitating MSCs migration and differentiation in a stabilized fracture mouse model

PTH1-34 improves bone healing by promoting angiogenesis and facilitating MSCs migration and differentiation in a stabilized fracture mouse model

Exploring the Biomaterial-Induced Secretome: Physical Bone Substitute Characteristics Influence the Cytokine Expression of Macrophages

Vertical bone augmentation with simultaneous implantation using deproteinized bovine bone block functionalized with a slow delivery of BMP‐2

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