Enemarkjacobsen1873

Extracellular vesicles (EVs) are particles originating from the exfoliation of the cellular membrane. They are involved in cell-to-cell and cell-to-matrix signaling, exchange of bioactive molecules, tumorigenesis and metastasis, among others. To mitigate the limited understanding of EVs transfer phenomena, we developed a simplistic model that mimics EVs and their interactions with cells and the extracellular matrix. The proposed model is a layer by layer (LbL) film built from the polycationic poly-l-lysine (PLL) and the glycosaminoglycan hyaluronic acid (HA) to provide ECM mimicry. Positively charged 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and N1,N1,N14,N14-tetramethyl-N1,N14-ditetradecyltetradecane-1,14-diaminium dibromide (GS14) liposomes were embedded in this construct to act as EVs analogs. To simulate EVs carrying substances, Nile Red was loaded as a model of lipophilic cargo molecules. The integration of each component was followed by quartz crystal microbalance measurements, which confirmed the immobilization of intact liposomes on the underlying (PLL/HA)3 soft film. The release of Nile Red from liposomes either embedded in the LbL construct or exposed at its surface revealed a fast first order release. This system was validated as a model for EV/cell interactions by incubation with breast cancer cells MDA-MB-231. We observed higher internalization for embedded liposomes when compared with surface-exposed ones, showcasing that the ECM mimic layers do not constitute a barrier to liposome/cell interactions but favor them.Mesenchymal stem cell (MSC)-spheroids have sparked significant interest in bone tissue engineering due to their resemblance to natural bone tissue, especially in terms of cell-cell and cell-extracellular matrix interactions. Many biomaterials or biomolecules have been incorporated into MSC-spheroids to enhance their osteogenic abilities. XMD892 In this respect, we assessed the osteogenic responses of MSC spheroids leveraged through the unique combination of collagen and black phosphorus (BP). The MSC spheroids were successfully constructed with 6 μg/mL collagen and/or a concentration gradient (0 μg/mL, 4 μg/mL, 8 μg/mL, and 16 μg/mL) of BP and were evaluated for MSC viability and their osteogenic differentiation over a time period of 14 days. Improved MSC viability and osteogenic ability were observed for the spheroids with collagen and BP at the concentration of 4 μg/mL and 8 μg/mL. Next, blank spheroids (Control) or the optimized MSC spheroids with 6 μg/mL collagen and 4 μg/mL BP (Col+BP4) were further encapsulated into two types of hydrogel scaffolds porous oligo[poly(ethylene glycol) fumarate] (OPF) hydrogel and hydroxyapatite-collagen I scaffold (HE-COL). The osteogenic abilities of these four groups were evaluated after 14 and 21 days of osteogenic induction. The MSC spheroids incorporated with collagen and BP implanted into OPF porous hydrogel (Col+BP/OPF) elicited a higher expression of Runx2, osteopontin, and alkaline phosphatase than blank spheroids implanted into OPF porous hydrogel (Control/OPF). Enhanced osteogenesis was also observed in the Col+BP/HE-COL group as compared to Control/HE-COL. Taken together, the results from this study showed the perspectives of collagen and BP incorporated MSC spheroids for the development of injectable cellular therapies for bone regeneration.Herein we explore a combination of anodization induced micro-roughness and biomimetic coating on pure magnesium (Mg) metal at different applied voltages to control adhesion, biodegradation, and corrosion performance in simulated body fluid solution. The anodic film was fabricated using two different potentials, 3 and 5 V, respectively, to create microroughness on the Mg surface. The microroughened Mg surface was subsequently coated with a biomimetic silk thin film; and the characteristics of the treated Mg-substrates were evaluated using various spectroscopic, microscopic, immersion, and electrochemical techniques. A number of independent measurements, including hydrogen evolution, weight loss and electrochemical methods were employed to assess the corrosion characteristics. The silk-coated anodized samples revealed dramatically reduced degradation rate in terms of volume of hydrogen gas generation and weight loss compared to the respective anodized but uncoated, which revealed that optimized biomimetic silk-coated Mg surface (anodized at 5 V and subsequently biomimetic silk-coated ANMg5V) exhibited the best corrosion performance among all other tested samples. The ANMg5V Silk showed the highest polarization resistance (46.12 kΩ·cm2), protection efficiency (>0.99) and lowest corrosion rate (only 0.017 mm/year) relative to untreated Mg (8.457 mm/year), and anodized Mg (1.039 for anodized at 3 V and 0.986 for anodized at 5 V) surface due to the formation of a pore-free dense biomimetic protective film over Mg surface. The results of the cytotoxicity test confirm that silk-coated samples are significantly less cytotoxic compared to bare and anodized Mg samples. With enhanced corrosion resistance and cytocompatibility, silk-coated Mg could be a potential material for clinical applications.Peripheral nerves injuries (PNIs) still associated with both clinical and social problems. Accordingly, tissue engineers' and surgeons' attentions have been drawn for finding efficient solutions. Herein, scaffolds based on silk fibroin (SF)/raffinose-grafted-GO (S.RafGO) nanocomposite were fabricated. Subsequently, PC12 cells growth in term of number and morphology were investigated on neat SF polymer, SF/GO (S.GO), and S.RafGO scaffolds. Characterization via scanning electron microscopy (SEM) exhibited more fibrous structures with few lamellar nanosheets for S.GO; although, S.RafGO showed extended lamellar with lower fibrous structure. Due to the incorporation of GO and raffinose-GO nanosheets into SF structure, electrical conductivity increased ~30 and 40%, respectively. Water contact angle data revealed that S.RafGO is more wettable than SF and S.GO. Real-time PCR technique detected higher expressions of the β-tubulin, MAP2 genes on S.RafGO scaffolds in comparison with S.GO and the control group. Immunocytochemistry staining studies confirmed the overexpression of neural-specific proteins including nestin, β-tubulin of S.GO, and S.RafGO nanocomposites in comparison with pure SF scaffolds.Applying multifunctional nanocarriers, comprising specifically traceable and tumor targeting moieties, has significantly increased in cancer theranostics. Herein, a novel targeted, trackable, and pH-responsive drug delivery system was fabricated based on glucosamine (GlcN) conjugated graphene quantum dots (GQDs) loaded by hydrophobic anticancer agent, curcumin (Cur), to evaluate its targeting and cytotoxicity potential against breast cancer cells with overexpression of GlcN receptors. The biocompatible photoluminescent GQDs were synthesized from graphene oxide through the green and facile oxidizing method. The structural and spectral characterizations of the as-prepared GQDs and Cur/GlcN-GQDs were investigated. The GQDs sizes were within 20-30 nm and showed less than ten layers. A pH-sensitive and sustained release behavior was also observed for the Cur loaded nanocarrier with a total release of 37% at pH 5.5 and 17% at pH 7.4 after 150 h. In vitro cellular uptake studies through fluorescence microscopy and flow cytometry exhibited stronger fluorescence for the targeted nanocarrier against MCF-7 cells compared to the non-targeted one, owing to higher cellular internalization via GlcN receptor-mediated endocytosis. Furthermore, the MTT assay results demonstrated the nontoxicity of the bare nanocarrier with the cell viability of above 94% even at concentrations as high as 50 μg·ml-1, while the Cur/GlcN-GQDs exhibited much more cytotoxicity against MCF-7 cells compared to Cur/GQDs. It is reasonable to conclude that this advanced multifunctional nano-assembly offers superior potential for breast cancer cell-targeted delivery.This work aimed to evaluate the effects of encapsulated tocotrienols (TRF) and caffeic acid (CA) in water-in-oil-in-water (W/O/W) multiple nanoemulsion with cisplatin towards cancer cells. This work is important considering the limited efficacy of cisplatin due to tumour resistance, as well as its severe side effects. A549 and HEP G2 cancer cell lines were utilised for evaluating the efficacy of the encapsulated W/O/W while HEK 293 normal cell line was used for evaluating the toxicity. TRF, CA and CIS synergistically improved apoptosis in the late apoptotic phase in A549 and HEP G2 by 23.1% and 24.9%, respectively. The generation of ROS was enhanced using TRFCACIS by 16.9% and 30.2% for A549 and HEP G2, respectively. Cell cycle analysis showed an enhanced cell arrest in the G0/G1 phase for both A549 and HEP G2. TRF, CA and CIS led to cell death in A549 and HEP G2. For HEK 293, ~33% cell viability was found when only CIS was used while >95% cell viability was observed when TRF, CA and CIS were used. This study demonstrates that the encapsulated TRF and CA in W/O/W with CIS synergistically improved therapeutic efficacy towards cancer cells, as well as lowered the toxicity effects towards normal cells.Orthopedic implant-associated infection constitutes one of the most devastating and challenging symptoms in the clinic. Implants without antimicrobial properties may become the harbourage for microbial colonization and biofilm formation, thus hindering normal bone regeneration processes. We had previously developed tannin modified HA (THA) as well as silver and tannin modified hydroxyapatite (HA) (Ag-THA) via a facile one-step and scalable process, and proven their antimicrobial performance in vitro. Herein, by compositing with non-antimicrobial polyurethane (PU), the in vivo anti-bacterial activity, osteoconductivity and osteoinductivity of PU/Ag-THA composite were investigated using an infected femoral condyle defect model on rat. PU/Ag-THA exhibited excellent in vivo antimicrobial activity, with the calculated bacteria fraction being reduced to lower than 3% at week 12 post operation. Meanwhile, PU/Ag-THA is also promising for bone regeneration under the bacteria challenge, evidenced by a final bone mineral density (BMD) ~0.6 times higher than that of the blank control at week 12. A continuous increase in BMD over time was observed in the PU/Ag-THA group, but not in the blank control and its non- or weak-antimicrobial counterparts (PU/HA and PU/THA), in which the growth rate of BMD declined after 8 weeks of operation. The enhanced osteoinductivity of PU/Ag-THA relative to blank control, PU/HA and PU/THA was also confirmed by the Runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) immunohistochemical staining. The above findings suggest that antimicrobial Ag-THA may serve as a promising and easy-to-produce antimicrobial mineral for the development of antimicrobial orthopedic composite implants to address the challenges in orthopedic surgeries, especially where infection may become a challenging condition to treat.Nowadays it is known that neural cells are capable of regenerating after brain injury, but their success highly depends on the local environment, including the presence of a biological structure to support cell proliferation and restore the lost tissue. Different chitosan-based biomaterials have been employed in response to this necessity. We hypothesized that hydrogels made of antioxidant compounds functionalizing chitosan could provide a suitable environment to home new cells and offer a way to achieve brain repair. In this work, the implantation of functionalized chitosan biomaterials in a brain injury animal model was evaluated. The injury consisted of mechanical damage applied to the cerebral cortex of Wistar rats followed by the implantation of four different chitosan-based biomaterials. After 15 and 30 days, animals underwent magnetic resonance imaging, then they were sacrificed, and the brain tissue was analyzed by immunohistochemistry. The proliferation of microglia and astrocytes increased at the lesion zone, showing differences between the evaluated biomaterials.