Background Low-intensity pulsed ultrasound (LIPUS) has been reported to accelerate fracture healing, but the mechanism is unclear and its efficacy needs to be further optimized. Ultrasound in combination with functionalized microbubbles has been shown to induce local shear forces and controllable mechanical stress in cells, amplifying the mechanical effects of LIPUS. Nanoscale lipid bubbles (nanobubbles) have high stability and good biosafety. However, the effect of LIPUS combined with functionalized nanobubbles on osteogenesis has rarely been studied. Results In this study, we report cyclic arginine-glycine-aspartic acid-modified nanobubbles (cRGD-NBs), with a particle size of ~ 500 nm, able to actively target bone marrow mesenchymal stem cells (BMSCs) via integrin receptors. cRGD-NBs can act as nanomechanical force generators on the cell membrane, and further enhance the BMSCs osteogenesis and bone formation promoted by LIPUS. The polymerization of actin microfilaments and the mechanosensitive transient receptor potential melastatin 7 (TRPM7) ion channel play important roles in BMSCs osteogenesis promoted by LIPUS/cRGD-NBs. Moreover, the mutual regulation of TRPM7 and actin microfilaments promote the effect of LIPUS/cRGD-NBs. The extracellular Ca2 + influx, controlled partly by TRPM7, could participated in the effect of LIPUS/cRGD-NBs on BMSCs. Conclusions The nanomechanical force generators cRGD-NBs could promote osteogenesis of BMSCs and bone formation induced by LIPUS, through regulation TRPM7, actin cytoskeleton, and intracellular calcium oscillations. This study provides new directions for optimizing the efficacy of LIPUS for fracture healing, and a theoretical basis for the further application and development of LIPUS in clinical practice.
A new method to compute the similarity of two blog posts is proposed in this paper. This method mainly has two parts including keywords extraction and semantic similarity measurement. During keywords extraction part, the method utilizes particular post features to extract keywords from one blog post with the aim to improve the correlation rate. In order to compute the similarity of any two blog posts more effectively, semantic similarity measurement part make use of personal ontology that denotes single post , the aim is to transform the blog post similarity into the personal ontology similarity. This method has already been applied in an original retrieval system which supports searching not only by several keywords, but also by a blog post (in the type of URL). The experimental results demonstrate that the proposed method is effective.
Purpose: Poly (lactic-co-glycolic acid)-based nanoparticles (PLGA NPs) have been widely used as the carrier for sustainable drug delivery. However, the drug release from the NPs was usually incomplete and uncontrollable. Herein, a low intensity pulsed ultrasound (LIPUS) assisted SDF-1/BMP-2@nanoparticles (S/B@NPs) system was fabricated to facilitate stem cell recruitment-osteogenesis for periodontal bone regeneration.Methods: In this work, S/B@NPs were prepared with double-emulsion synthesis method. Then the S/B release profile from NPs was evaluated with or without low intensity pulsed ultrasound treatment. Afterwards, the stem cell recruiting and osteoinductive capacities of LIPUS-S/B@NPs were detected with human periodontal ligament cells (hPDLCs) in vitro and in a rat periodontal bone defect model.Results: The results indicated that S/B@NPs were successfully prepared and LIPUS could effectively regulate the release of S/B and increase their final releasing amount. Moreover, LIPUS-S/B@NPs system significantly promoted hPDLCs migrating and osteogenesis in vitro and recruiting rBMSCs to the rat periodontal defect and facilitated bone regeneration in vivo.Conclusion: Our LIPUS assisted S/B@NPs system can effectively facilitate stem cell recruitment and periodontal bone regeneration. Considering its reliable safety and therapeutic effect on bone fracture, LIPUS, as an adjuvant therapy, holds great potential in the regulation of drug delivery systems for bone healing.
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