Large and Externally Positioned Ligand-Coated Nanopatches Facilitate the Adhesion-Dependent Regenerative Polarization of Host Macrophages.

Macrophages can associate with extracellular matrix (ECM) demonstrating nanosequenced cell-adhesive RGD ligand. In this study, we devised barcoded materials composed of RGD-coated gold and RGD-absent iron nanopatches to show various frequencies and position of RGD-coated nanopatches with similar areas of iron and RGD-gold nanopatches that maintain macroscale and nanoscale RGD density invariant. Iron patches were used for substrate coupling. Both large (low frequency) and externally positioned RGD-coated nanopatches stimulated robust attachment in macrophages, compared with small (high frequency) and internally positioned RGD-coated nanopatches, respectively, which mediate their regenerative/anti-inflammatory M2 polarization. The nanobarcodes exhibited stability in vivo. We shed light into designing ligand-engineered nanostructures in an external position to facilitate host cell attachment, thereby eliciting regenerative host responses.

Independent Tuning of Nano-Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells.

The native extracellular matrix (ECM) can exhibit heterogeneous nano-sequences periodically displaying ligands to regulate complex cell-material interactions in vivo. Herein, an ECM-emulating heterogeneous barcoding system, including ligand-bearing Au and ligand-free Fe nano-segments, is developed to independently present tunable frequency and sequences in nano-segments of cell-adhesive RGD ligand. Specifically, similar exposed surface areas of total Fe and Au nano-segments are designed. Fe segments are used for substrate coupling of nanobarcodes and as ligand-free nano-segments and Au segments for ligand coating while maintaining both nanoscale (local) and macroscale (total) ligand density constant in all groups. Low nano-ligand frequency in the same sequences and terminally sequenced nano-ligands at the same frequency independently facilitate focal adhesion and mechanosensing of stem cells, which are collectively effective both in vitro and in vivo, thereby inducing stem cell differentiation. The Fe/RGD-Au nanobarcode implants exhibit high stability and no local and systemic toxicity in various tissues and organs in vivo. This work sheds novel insight into designing biomaterials with heterogeneous nano-ligand sequences at terminal sides and/or low frequency to facilitate cellular adhesion. Tuning the electrodeposition conditions can allow synthesis of unlimited combinations of ligand nano-sequences and frequencies, magnetic elements, and bioactive ligands to remotely regulate numerous host cells in vivo.

Influence of Ultrasound and Magnetic Field Treatment Time on Carcinoma Cell Inhibition with Drug Carriers: An in Vitro Study.

The influence of exposing carcinoma cells to a static magnetic field (SMF) and low-intensity pulsed ultrasound (LIPUS), for different durations (15-45 min/d), in the presence of magnetic and non-magnetic drug carriers, on their in vitro inhibition is examined. Increasing the exposure time by 15 min/d decreased the culture duration by 24 h to achieve the same level of inhibition in colon (HCT116) and hepatocellular (HepG2) cells. Cell cycle analysis revealed enhanced cellular blockage in G1 and S phases with SMF + LIPUS exposure, and exposure for 45 min/d completely suppressed the S → G2 transition. Apoptosis of both types of cells increased with SMF + LIPUS treatment time, and HepG2 cells exhibited elevated necrosis with >30 min/d exposure. HepG2 cells also had higher amounts of reactive oxygen species (seven- to eightfold) than HCT116 cells (two- to sixfold), suggesting treatment effectiveness is cell and drug carrier dependent. The accelerated cellular activities are attributed to the enhanced internalization of drug carriers as a consequence of destabilized cellular membranes caused by the SMF + LIPUS-generated mechanical and electrical stimuli.

In Situ Magnetic Control of Macroscale Nanoligand Density Regulates the Adhesion and Differentiation of Stem Cells.

Developing materials with remote controllability of macroscale ligand presentation can mimic extracellular matrix (ECM) remodeling to regulate cellular adhesion in vivo. Herein, we designed charged mobile nanoligands with superparamagnetic nanomaterials amine-functionalized and conjugated with polyethylene glycol linker and negatively charged RGD ligand. We coupled negatively a charged nanoligand to a positively charged substrate by optimizing electrostatic interactions to allow reversible planar movement. We demonstrate the imaging of both macroscale and in situ nanoscale nanoligand movement by magnetically attracting charged nanoligand to manipulate macroscale ligand density. We show that in situ magnetic control of attracting charged nanoligand facilitates stem cell adhesion, both in vitro and in vivo, with reversible control. Furthermore, we unravel that in situ magnetic attraction of charged nanoligand stimulates mechanosensing-mediated differentiation of stem cells. This remote controllability of ECM-mimicking reversible ligand variations is promising for regulating diverse reparative cellular processes in vivo.

Dynamics of organic matter decomposition during vermicomposting of banana stem waste using Eisenia fetida.

A better understanding of how dynamics of physical and chemical changes occur during vermicomposting process would be helpful for determining the stability and maturity of vermicompost. For improving the knowledge about this issue several instrumental techniques were used in the present study to analyse the physical and chemical changes as a function of vermicomposting time of banana stem waste (BS) spiked with cow dung (CD) in different proportions using earthworm Eisenia fetida. Chemical analysis by ICP-AES showed gradual increase in the plant nutrients (P, Ca, K, Mg, Fe) up to 60 day of vermicomposting in all the treatments. But among different treatments, K, Mg and Fe were considerably higher in the BS2CD1 blend. The FTIR showed strong NO stretching vibration with increasing BS content signifying the presence of nitrate in the final compost. The TG analysis of final BS-CD composts described the lower mass loss (52-55%) in the final compared to the initial stage due to high level of humification by earthworms. The maturity of the final compost was confirmed by DSC analysis which exhibited lowering of relative intensity of exothermic peaks related to the easily degradable material at 320-330 °C and complex organic moieties at 495-530 °C. Decrease in the humification index (Q4/6, Q2/4, Q2/6) at 60 day confirmed the stability of vermicomposts. All the treatments showed <2 mg CO2-C g-1 vermicompost C day-1 respiration rates and >70% germination indices (GI) for rice and pea seeds. These findings defined a clear comparison between the treatments during vermicomposting in terms of stability and maturity and revealed that BS2CD1 can be utilized as nutrient-rich stable compost for enhanced crop production.

In Vitro Carcinoma Treatment Using Magnetic Nanocarriers under Ultrasound and Magnetic Fields.

Nowadays, tumor hypoxia has become a more predominant problem for diagnosis as well as treatment of cancer due to difficulties in delivering chemotherapeutic drugs and their carriers to these regions with reduced vasculature and oxygen supply. In such cases, external physical stimulus-mediated drug delivery, such as ultrasound and magnetic fields, would be effective. In this work, the effect of simultaneous exposure of low-intensity pulsed ultrasound and static magnetic field on colon (HCT116) and hepatocellular (HepG2) carcinoma cell inhibition was assessed in vitro. The treatment, in the presence of anticancer drug, with and without magnetic carrier, significantly increased the reactive oxygen species production and hyperpolarized the cancer cells. As a result, a significant increase in cell inhibition, up to 86%, was observed compared to 50% inhibition with bare anticancer drug. The treatment appears to have relatively more effect on HepG2 cells during the initial 24 h than on HCT116 cells. The proposed treatment was also found to reduce cancer cell necrosis and did not show any inhibitory effect on healthy cells (MC3T3). Our in vitro results suggest that this approach has strong application potential to treat cancer at lower drug dosage to achieve similar inhibition and can reduce health risks associated with drugs.