Bioinspired Nanovesicles Convert the Skeletal Endothelium-Associated Secretory Phenotype to Treat Osteoporosis

Cui, Yongzhi; Li, Zhongying; Guo, Yuanyuan; Qi, Xiangbei; Yang, Yueping; Xiong, Jia; Li, Rui; Shi, Jingyu; Gao, Weihang; Ren, Zhengwei; Liu, Guohui; Ye, Qingsong; Zhang, Zhiping; Fu, Dehao

doi:10.1021/acsnano.2c03781

Cited by 33 publications

(16 citation statements)

References 60 publications

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“…In addition, bone-targeting molecules could also be coupled with nanomaterials to increase their skeletal accumulation. Bioinspired exosomes or nanovesicles have been fabricated with abundant bone-targeting molecules present on their surface, showing 2–10 times more accumulation in the bone (mainly femur) compared to plain nanovesicles ( Cui et al, 2022a ; Cui et al, 2022b ).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal in vivo biodistribution of nano and micro sized hydroxyapatite particles implanted in a bone defect

Liu

Sebastian

Huang

et al. 2022

Front. Bioeng. Biotechnol.

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Hydroxyapatite (HA) has been widely used as a bone substitute and more recently as a carrier for local delivery of bone targeted drugs. Majority of the approved HA based biomaterials and drug carriers comprise of micrometer sized particulate HA (mHA) or granules and can therefore only be used for extracellular drug release. This shortcoming could be overcome with the use of cell penetrating HA nanoparticles (nHA) but a major concern with the clinical use of nHA is the lack of data on its in vivo biodistribution after implantation. In this study, we aimed to study the in vivo biodistribution of locally implanted nHA in a clinically relevant tibial void in rats and compare it with mHA or a combination of mHA and nHA. To enable in vivo tracking, HA particles were first labelled with 14C-zoledronic acid (14C-ZA), known to have a high binding affinity to HA. The labelled particles were then implanted in the animals and the radioactivity in the proximal tibia and vital organs was detected at various time points (Day 1, 7 and 28) post-implantation using scintillation counting. The local distribution of the particles in the bone was studied with micro-CT. We found that majority (>99.9%) of the implanted HA particles, irrespective of the size, stayed locally at the implantation site even after 28 days and the findings were confirmed using micro-CT. Less than 0.1% radioactivity was observed in the kidney and the spleen at later time points of day 7 and 28. No pathological changes in any of the vital organs could be observed histologically. This is the first longitudinal in vivo HA biodistribution study showing that the local implantation of nHA particles in bone is safe and that nHA could potentially be used for localized drug delivery.

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Section: Discussionmentioning

confidence: 99%

Longitudinal in vivo biodistribution of nano and micro sized hydroxyapatite particles implanted in a bone defect

Liu

Sebastian

Huang

et al. 2022

Front. Bioeng. Biotechnol.

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“…In addition, bioinspired nanovesicles from human induced pluripotent stem cell-derived endothelial cells were engineered to secret cytokines, favoring osteogenesis and anti-inflammation. It induced the osteogenic differentiation of the bone mesenchymal stem cells (BMSCs) and the M1-macrophage-dominant pro-inflammatory microenvironment in the osteoporotic bones in ovariectomized mice [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Ageing and Osteoarthritis Synergically Affect Human Synoviocyte Cells: An In Vitro Study on Sex Differences

Veronesi

Contartese

Borsari

et al. 2022

JCM

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Osteoarthritis is a chronic inflammatory disease that affects all of the joints, especially those of the elderly. Aging is a natural and irreversible biological process implicated in the pathophysiology of many chronic diseases, such as osteoarthritis. Inflammation and oxidative stress are the main factors involved in osteoarthritis and aging, respectively, with the production of several pro-inflammatory cytokines such as Interleukin 1β (IL1β) and reactive oxygen species. The aim of the study was to set-up an in vitro model of osteoarthritis and aging, focusing on the sex differences by culturing male and female fibroblast-like synoviocytes (FLSs) with IL1β, hydrogen peroxide (H2O2), IL1β+H2O2 or a growth medium (control). IL1β+H2O2 reduced the cell viability and microwound healing potential, increased Caspase-3 expression and reactive oxygen species and IL6 production; IL1β increased IL6 production more than the other conditions did; H2O2 increased Caspase-3 expression and reactive oxygen species production; Klotho expression showed no differences among the treatments. The FLSs from female donors demonstrated a better response capacity in unfavorable conditions of inflammation and oxidative stress than those from the male donors did. This study developed culture conditions to mimic the aging and osteoarthritis microenvironment to evaluate the behavior of the FLSs which play a fundamental role in joint homeostasis, focusing on the sex-related aspects that are relevant in the osteoarthritis pathophysiology.

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“…Generally, physical manipulation is performed by directly exerting physical forces on the parent cells by electroporation and extrusion ( Richter et al, 2021 ), thereby optimizing EVs derived from them. Cui et al (2022) reported bioinspired nanovesicles prepared from human iPSC-derived endothelial cells under hypoxia culture through an extrusion approach. Abundant membrane C-X-C motif chemokine receptor 4 conferred these nanovesicles bone-targeting ability and the endothelial homology facilitated the bone marrow endothelial cells tropism.…”

Section: Application Of Engineering Modified Extracellular Vesicles I...mentioning

confidence: 99%

The potential therapeutic role of extracellular vesicles in critical-size bone defects: Spring of cell-free regenerative medicine is coming

Liu

Sun²,

An³

et al. 2023

Front. Bioeng. Biotechnol.

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In recent years, the incidence of critical-size bone defects has significantly increased. Critical-size bone defects seriously affect patients’ motor functions and quality of life and increase the need for additional clinical treatments. Bone tissue engineering (BTE) has made great progress in repairing critical-size bone defects. As one of the main components of bone tissue engineering, stem cell-based therapy is considered a potential effective strategy to regenerate bone tissues. However, there are some disadvantages including phenotypic changes, immune rejection, potential tumorigenicity, low homing efficiency and cell survival rate that restrict its wider clinical applications. Evidence has shown that the positive biological effects of stem cells on tissue repair are largely mediated through paracrine action by nanostructured extracellular vesicles (EVs), which may overcome the limitations of traditional stem cell-based treatments. In addition to stem cell-derived extracellular vesicles, the potential therapeutic roles of nonstem cell-derived extracellular vesicles in critical-size bone defect repair have also attracted attention from scholars in recent years. Currently, the development of extracellular vesicles-mediated cell-free regenerative medicine is still in the preliminary stage, and the specific mechanisms remain elusive. Herein, the authors first review the research progress and possible mechanisms of extracellular vesicles combined with bone tissue engineering scaffolds to promote bone regeneration via bioactive molecules. Engineering modified extracellular vesicles is an emerging component of bone tissue engineering and its main progression and clinical applications will be discussed. Finally, future perspectives and challenges of developing extracellular vesicle-based regenerative medicine will be given. This review may provide a theoretical basis for the future development of extracellular vesicle-based biomedicine and provide clinical references for promoting the repair of critical-size bone defects.

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Bioinspired Nanovesicles Convert the Skeletal Endothelium-Associated Secretory Phenotype to Treat Osteoporosis

Cited by 33 publications

References 60 publications

Longitudinal in vivo biodistribution of nano and micro sized hydroxyapatite particles implanted in a bone defect

Longitudinal in vivo biodistribution of nano and micro sized hydroxyapatite particles implanted in a bone defect

Ageing and Osteoarthritis Synergically Affect Human Synoviocyte Cells: An In Vitro Study on Sex Differences

The potential therapeutic role of extracellular vesicles in critical-size bone defects: Spring of cell-free regenerative medicine is coming

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