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Adipose-Derived Stem Cells Depending on Electrospun Biomimetic Scaffold Mediated Endothelial Difference Facilitating Rejuvination and Repair involving Belly Wall structure Defects by way of HIF-1α/VEGF Process.
Hybrid superparamagnetic microspheres with bone-like composition, previously developed by a bio-inspired assembling/mineralization process, are evaluated for their ability to uptake and deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in therapeutically-relevant doses along with prolonged release profiles. The comparison with hybrid non-magnetic and with non-mineralized microspheres highlights the role of nanocrystalline, nanosize mineral phases when they exhibit surface charged groups enabling the chemical linking with the growth factor and thus moderating the release kinetics. All the microspheres show excellent osteogenic ability with human mesenchymal stem cells whereas the hybrid mineralized ones show a slow and sustained release of rhBMP-2 along 14 days of soaking into cell culture medium with substantially bioactive effect, as reported by assay with C2C12 BRE-Luc cell line. read more It is also shown that the release extent can be modulated by the application of pulsed electromagnetic field, thus showing the potential of remote controlling the bioactivity of the new micro-devices which is promising for future application of hybrid biomimetic microspheres in precisely designed and personalized therapies.Bio-functional fillers including bio-ceramic, degradable metallic and composite particles are commonly introduced into bone tissue engineering (BTE) scaffolds to endow the materials with specific biological functions for enhanced bone defect therapy. In this work, MgO nanoparticles (NPs) were employed as a potential platform for precise loading and sustained release of Ag+. The results showed that MgO NPs possessed strong adsorption capacity (almost 100%) towards Ag+ in AgNO3 solutions with different concentrations (0.1, 1 and 10 mM). After the adsorption of Ag+ in AgNO3 solutions, cube-shaped MgO NPs transformed to lamella-structured nano-composites (NCs) composed of Mg(OH)2 and Ag2O, which were referred as MgO-xAg (x = 0.1, 1 or 10) NCs depending on the employed concentration of AgNO3 solution. After being suspended in distilled water, as-prepared positively charged NCs underwent a fast degradation process during the initial 4 days. From day 4 and 14, steady release behaviors of Mg2+ and/or Ag+ from the NCs were noticed. With the lowest loading amount of Ag+, MgO-0.1Ag NCs did not exhibit significant modulatory effect on SaOS-2 cell response. On the contrary, MgO-10Ag NCs loaded with the highest amount of Ag+ showed significant cyto-toxicity towards SaOS-2 cells. With appropriate amount of Ag+ loading, MgO-1Ag NCs showed significantly stimulatory effects on SaOS-2 cell proliferation and differentiation. This is evidenced by the enhanced cell viability, alkaline phosphatase (ALP) activity and collagen (COL) production as well as the gene expressions of ALP, COL and osteoprotegerin (OPG) in MgO-1Ag group. Moreover, MgO-1Ag exhibited strong bactericidal capacity against both Escherichia coli and Staphylococcus aureus. Together, the results indicate that MgO could be employed as a potential platform for precise loading and sustained release of Ag+. MgO-1Ag NCs are promising to be used as bio-functional fillers in BTE scaffolds for simultaneously promoted osteogenesis and bacterial killing.The aim of this study was to design and develop a novel hybrid formulation based on lipid nanocapsules containing bevacizumab (BVZ), an effective therapeutic antibody, on the surface and triamcinolone acetonide (TA) in the inner core (BVZ-TA-LNC) intended to improve ocular therapy. Hence, a phase inversion-insertion one step method was developed to drug loading and surface modification of lipid nanocapsules by post-insertion of a bifunctional polymer, followed by antibody coupling using "click" chemistry. The covalent bond and antibody capacity binding to its specific antigen were confirmed by thermal analysis and immunoassay, respectively. BVZ-TA-LNC presented nanometric size (102 nm), negative surface potential (-19 mV) and exhibiting 56% of TA in the lipid core. BVZ-TA-LNC tended to prevent the endothelial cell migration and significantly prevented the capillary formation induced by the vascular endothelium growth factor (VEGF). The novel hybrid system allowed the co-loading of two different therapeutic molecules and may be promising to improve the therapy of eye disorders that occur with inflammation and/or neovascularization.Osteomyelitis is a major challenge in bone surgery and conventional treatment is frequently ineffective to control the infection, with an alternative approach being required. In the present work, a heparinized nanohydroxyapatite/collagen biocomposite was produced in granular form, and loaded with vancomycin, to work as a local drug delivery system for osteomyelitis and as a bone substitute. This strategy involves the local delivery of high concentrations of vancomycin, to eradicate the infection. Additionally, these granules work as a scaffold with regenerative properties, to induce bone regeneration after antibiotic release. The heparinized nanohydroxyapatite/collagen granular bone substitute was produced using two different sintering temperatures to study their effect on granules properties and on vancomycin release profile. Morphological, topographic, chemical and mechanical characterization were carried out for granules sintered at both temperatures and some relevant differences were found. The mechanical strength was increased by several orders of magnitude with increasing sintering temperature, being able to maintain their porous macrostructure and withstand important processes for their commercialization such as packaging, shipping and surgical manipulation. The nanohydroxyapatite/collagen granules were able to release high concentrations of vancomycin, always above MIC, for 19 days. The released antibiotic was able to eradicate both planktonic and sessile methicillin-resistant Staphylococcus aureus. The cytotoxicity was assessed according to ISO 10993-52009 and the granules sintered at higher temperature showed no cytotoxic effect. Considering these results nanohydroxyapatite/collagen biocomposite loaded with vancomycin is a promising solution for osteomyelitis treatment.
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