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Kjellerup Whitfield posted an update 10 months, 2 weeks ago
This study aimed to explore the in vitro and in vivo roles of macrophages in the osteogenesis stimulated by BMP2-CPC. In vitro, the alteration of macrophage polarization and cytokine secretion induced by BMP2-CPC or CPC was investigated. The influence of conditioned medium derived from BMP2-CPC- or CPC-stimulated macrophages on the migration and osteogenic differentiation of MSCs were evaluated. The in vivo relationship between macrophage polarization and osteogenesis was examined in a rabbit calvarial defect model. The in vitro results indicated that BMP2-CPC and CPC induced different patterns of macrophage polarization and subsequently resulted in distinct patterns of cytokine expression and secretion. Conditioned medium derived from BMP2-CPC- or CPC-stimulated macrophages both exhibited apparent osteogenic effect on MSCs. Notably, BMP2-CPC induced more M2-phenotype polarization and higher expression of anti-inflammatory cytokines and growth factors than did CPC, which led to the better osteogenic effect of conditioned medium derived from BMP2-CPC-stimulated macrophages. The rabbit calvarial defect model further confirmed that BMP2-CPC facilitated more bone regeneration than CPC did by enhancing M2-phenotype polarization in local macrophages and then alleviating inflammatory reaction. In conclusion, this study revealed that the favorable immunoregulatory property of BMP2-CPC contributed to the strong osteogenic capability of BMP2-CPC by modulating macrophage polarization.The combined use of nanohydrogels (NHGs) and quantum dots (QDs) has resulted in the development of a nanoscaled drug delivery system (DDS) with fluorescence imaging potential. NHG-QDs composite loaded with anti-cancer drugs could be applied as an effective theranostics for simultaneous diagnosis and therapy of cancer cells. Here, we report on the synthesis of NHG-QDs nanosystem (NS) conjugated with an amino-modified MUC-1 aptamer (Ap) and loaded with hydrophobic paclitaxel (PTX). To effectively target and eradicate breast cancer MCF-7 cells, the nanocomposite was further loaded with the inhibitor of lactate dehydrogenase (LDH), sodium oxamate (SO) (Ap-NHG-QDs-PTX-SO) to inhibit the conversion of pyruvate to lactate via LDH and disrupting glycolysis. Results obtained from in vitro analysis (MTT assay, apoptosis/necrosis assessment, evaluation of mitochondria targeting, and gene expression profiling) revealed that Ap-NHG-QDs-PTX-SO NS could significantly target and inhibit MCF-7 cells and also induce mitochondria-mediated apoptosis. Collectively, the Ap-NHG-QDs-PTX-SO NS is proposed to serve as a robust theranostics for simultaneous imaging and therapy of breast cancer and other types of solid tumors.Drug delivery for treatment of chronic diseases relies on the effective delivery of payload materials into the target cells in a long-term release. In this context, the present study investigated hybrid microgels as platforms to carry nanoparticles to drug delivery. Hybrid microgels were produced with silk fibroin (SF) and chondroitin sulfate (CS), and alginate (ALG) by droplet microfluidics. this website ALG/SF, ALG/CS, and ALG/CS/SF microgels, ranging from 70-90 μm, were tested to encapsulate two model nanoparticles, polystyrene latex beads in pristine form (NPs) and NPs coated with bovine serum albumin (NPs-BSA) to simulate hydrophobic and hydrophilic nanocarriers, respectively. IR spectroscopy and fluorescence microscopy analysis confirmed the presence of SF and CS within ALG-based microgels revealing marked differences in their morphology and physicochemical properties. The release profiles of model nanoparticles revealed to be dependent on microgels composition and physicochemical properties. These findings show that SF ternary hybrid microgels facilitated the entrapment of hydrophobic nanocarriers with encapsulation efficiency (EE) from 83 to 98% keeping a better sustainable profile release than nonhybrid ALG microgels. Besides, CS improved the carriage of NPs-BSA (EE = 85%) and their profile release. The results highlight the versatility and tunable properties of these biobased microgels, being a good strategy to be used as an efficient platform in using macro and nanoencapsulated systems for drug delivery.This work is aimed to develop a biocompatible, bactericidal and mechanically stable biomaterial to overcome the challenges associated with calcium phosphate bioceramics. The influence of chemical composition on synthesis temperature, bioactivity, antibacterial activity and mechanical stability of least explored calcium silicate bioceramics was studied. The current study also investigates the biomedical applications of rankinite (Ca3Si2O7) for the first time. Sol-gel combustion method was employed for their preparation using citric acid as a fuel. Differential thermal analysis indicated that the crystallization of larnite and rankinite occurred at 795 °C and 1000 °C respectively. The transformation of secondary phases into the desired product was confirmed by XRD and FT-IR. TEM micrographs showed the particle size of larnite in the range of 100-200 nm. The surface of the samples was entirely covered by the dominant apatite phase within one week of immersion. Moreover, the compressive strength of larnite and rankinite was found to be 143 MPa and 233 MPa even after 28 days of soaking in SBF. Both samples prevented the growth of clinical pathogens at a concentration of 2 mg/mL. Larnite and rankinite supported the adhesion, proliferation and osteogenic differentiation of hBMSCs. The variation in chemical composition was found to influence the properties of larnite and rankinite. The results observed in this work signify that these materials not only exhibit faster biomineralization ability, excellent cytocompatibility but also enhanced mechanical stability and antibacterial properties.Biomaterials with anti-infective coatings are usually found to suffer from low cyto-compatibility and therefore, development of a stable, effective polymeric anti-bacterial substrate without compromising the biocompatibility is still an unmet challenge. Addressing this, a simple strategy for developing non-leaching antibacterial coating on a biodegradable substrate is reported here. The strategy can be utilized for mitigating serious biomedical implant related complications arising from generation of biocide resistant bacterial strains, losing antibacterial activity over time etc. without significantly compromising the cytocompatibility of the biomaterials. To develop the infection resistant yet cytocompatible biomaterials comprised of tartaric acid based biodegradable aliphatic polyester, we have primarily focussed on attaching anti-infective polymer brushes such as poly (2-hydroxyethyl methacrylate) (PHEMA), poly (poly (ethylene glycol) methacrylate) (PPEGMA) and poly[(2-methacryloyloxyethyl] trimethyl ammonium chloride) (PMETA) on hydroxyl functionalized polyester substrate via surface initiated atom transfer radical polymerization (SIATRP).