Movement is a key characteristic of higher organisms. During mammalian embryogenesis fetal movements have been found critical to normal tissue development. On the single cell level, however, our current understanding of stem cell differentiation concentrates on inducing factors through cytokine mediated biochemical signaling. In this study, human mesenchymal stem cells and chondrogenesis were investigated as representative examples. We show that pressureless, soft mechanical stimulation precipitated by the cyclic deformation of soft, magnetic hydrogel scaffolds with an external magnetic field, can induce chondrogenesis in mesenchymal stem cells without any additional chondrogenesis transcription factors (TGF-β1 and dexamethasone). A systematic study on the role of movement frequency revealed a classical dose-response relationship for human mesenchymal stem cells differentiation towards cartilage using mere mechanical stimulation. This effect could even be synergistically amplified when exogenous chondrogenic factors and movement were combined.
Background Distal flap necrosis is a frequent complication of perforator flaps. Advances in nanotechnology offer exciting new therapeutic approaches. Anti-inflammatory and neo-angiogenic properties of certain metal oxides within the nanoparticles, including bioglass and ceria, may promote flap survival. Here, we explore the ability of various nanoparticle formulations to increase flap survival in a rat model. Materials and methods A 9 x 3 cm dorsal flap based on the posterior thigh perforator was raised in 32 Lewis rats. They were divided in 4 groups and treated with different nanoparticle suspensions: I–saline (control), II–Bioglass, III–Bioglass/ceria and IV–Zinc-doped strontium-substituted bioglass/ceria. On post-operative day 7, planimetry and laser Doppler analysis were performed to assess flap survival and various samples were collected to investigate angiogenesis, inflammation and toxicity. Results All nanoparticle-treated groups showed a larger flap survival area as compared to the control group (69.9%), with groups IV (77,3%) and II (76%) achieving statistical significance. Blood flow measurements by laser Doppler analysis showed higher perfusion in the nanoparticle-treated flaps. Tissue analysis revealed higher number of blood vessels and increased VEGF expression in groups II and III. The cytokines CD31 and MCP-1 were decreased in groups II and IV. Conclusions Bioglass-based nanoparticles exert local anti-inflammatory and neo-angiogenic effects on the distal part of a perforator flap, increasing therefore its survival. Substitutions in the bioglass matrix and trace metal doping allow for further tuning of regenerative activity. These results showcase the potential utility of these nanoparticles in the clinical setting.
Radiotherapy is a key pillar of solid cancer treatment. Despite a high level of conformal dose deposition, radiotherapy is limited due to co-irradiation of organs at risk and subsequent normal tissue toxicities. Nanotechnology offers an attractive opportunity for increasing the efficacy and safety of cancer radiotherapy. Leveraging the freedom of design and the growing synthetic capabilities of the nanomaterial-community, a variety of engineered nanomaterials have been designed and investigated as radiosensitizers or radioenhancers. While research so far has been primarily focused on gold nanoparticles and other high atomic number materials to increase the absorption cross section of tumor tissue, recent studies are challenging the traditional concept of high-
PURPOSE: Seroma formation is a common postoperative complication, and bioglass/ceria-based nanoparticles (NPs) have been a recent focus for possible treatment. Although significant early seroma reduction has been shown, little is known about long-term efficacy of NPs. The aim of this study was to assess the long-term effects of NPs in reducing seroma formation. METHODS: Seroma was surgically induced bilaterally in 20 Lewis rats. On postoperative day (POD) 7, seromas were aspirated on both sides. In 10 rats, one side was treated with NPs, while the contralateral side received only NP carrier solution. In the other 10 rats, one side was treated with fibrin glue, while the other was left untreated. Seroma fluid, blood and tissue samples were obtained at defined time points. Biochemical, histopathological and immunohistochemical assessments were made. RESULTS: NP-treated sides showed no macroscopically visible seroma formation after application on POD 7, compared to fibrin-treated sides, where 60% of the rats had seromas on POD 14, and 50% on POD 21. At endpoint (POD 42), NP-treated sides showed significant macroscopic differences compared to other groups: cavity absence and increased fibrous adhesions. Histologically, there were increased macrophage groupings and collagen type 1 (COL1) depositions in the superficial capsule in NP-treated sides. CONCLUSION: Not only did NPs significantly reduce early manifestations of seroma and show an anti-inflammatory response, they also led to increased adhesion formation long term, suggesting a decreased recurrence risk for seroma formation. These findings emphasize both the adhesive properties of NPs and their clinical therapeutic potential.
The effect of particle interactions on the signal stability of magnetic particle imaging (MPI) and spectroscopy is analyzed. We show that our pre-aggregated flame-made nanoparticles outperform a commercial agglomerating MPI tracer.
Recent studies report promising results regarding extracorporeal magnetic separation-based blood purification for the rapid and selective removal of disease-causing compounds from whole blood. High molecular weight compounds, bacteria and cells can be eliminated from blood within minutes, hence offering novel treatment strategies for the management of intoxications and blood stream infections. However, risks associated with incomplete particle separation and the biological consequences of particles entering circulation remain largely unclear. This article discusses the promising future of magnetic separation-based purification while keeping important safety considerations in mind.
The delivered nanoparticle dose to cells in vitro may depend on nanoparticle sedimentation rate. Here, the conditions under which optical absorption spectroscopy can be used to quantify the deposited nanoparticle dose in vitro are investigated.Nanoparticle cytotoxicity in both upright and inverted cell culture orientations is studied in the presence and absence of serum.Dissolvable nanoparticles, such as ZnO, exhibit no difference in upright and inverted cultures due to dissolved Zn(2+) ions that dominate cytotoxicity. Insoluble nanoparticles, however, exhibit different sedimentation rates and deposited doses that are linked to the observed cytotoxicity.The combined use of upright-inverted cell orientations and optical absorption spectroscopy can provide a simple experimental approach to interpret in vitro nano-biointeractions.
Abstract This work describes a magnetic separation‐based approach using polymyxin B‐functionalized metal alloy nanomagnets for the rapid elimination of endotoxins from human blood in vitro and functional assays to evaluate the biological relevance of the blood purification process. Playing a central role in gram‐negative sepsis, bacteria‐derived endotoxins are attractive therapeutic targets. However, both direct endotoxin detection in and removal from protein‐rich fluids remains challenging. We present the synthesis and functionalization of ultra‐magnetic cobalt/iron alloy nanoparticles and a magnetic separation‐based approach using polymyxin B‐functionalized nanomagnets to remove endotoxin from human blood in vitro . Conventional chromogenic Limulus Amebocyte Lysate assays confirm decreased endotoxin activity in purified compared to untreated samples. Functional assays assessing key steps in host defense against bacteria show an attenuated inflammatory mediator expression from human primary endothelial cells in response to purified blood samples compared to untreated blood and less chemotactic activity. Exposing Escherichia coli ‐positive blood samples to polymyxin B‐functionalized nanomagnets even impairs the ability of gram‐negative bacteria to form colony forming units, thus making magnetic separation based blood purification a promising new approach for future sepsis treatment.