Weilu Cheng

Preparation of pH-responsive mesoporous hydroxyapatite nanoparticles for intracellular controlled release of an anticancer drug

A well-defined core-shell nano-carrier (PAA-MHAPNs) was successfully synthesized based on a graft-onto method by using mesoporous hydroxyapatite nanoparticles (MHAPNs) as the core and polyacrylic acid (PAA) as the shell. Given that MHAPNs are regarded as one of the most promising drug delivery vehicles due to their excellent performance and the nature of their cancer cell anti-proliferative effect, and the grafted PAA, as a pH-responsive switch, could improve the loading amount of the drug doxorubicin hydrochloride (DOX) effectively by electrostatic interactions, all these advantages mean that the designed models show promise for application in pH-responsive drug delivery systems. The loading content and entrapment efficiency of DOX could reach up to 3.3% and 76%, respectively. The drug release levels of the constructed DOX@PAA-MHAPNs were low under normal physiological conditions (pH 7.4), but they could be increased significantly with a decrease of pH. Cytotoxicity assays indicated that the PAA-MHAPNs was biocompatible, and more importantly, the DOX@PAA-MHAPNs demonstrated an obvious ability to induce apoptosis of cancer cells. Overall, the synthesized systems should show great potential as drug nanovehicles with excellent biocompatibility, high drug loading, and pH-responsive features for future intracellular drug delivery.

Redox-responsive nanoreservoirs based on collagen end-capped mesoporous hydroxyapatite nanoparticles for targeted drug delivery

Mesoporous hydroxyapatite (MHAp) nanoparticles have great potential in nanoscaled delivery devices due to their excellent biocompatibility, nontoxicity and high surface areas. In order to achieve targeting based on cell-specific recognition and site directed, timed and quantitatively controlled drug release to malignant cells, redox-responsive nanoreservoirs based on MHAp (LA-Col-S-S-MHAp) were fabricated by using lactobionic acid-conjugated collagen (LA-Col) as a cap, disulfide bonds as intermediate linkers and MHAp as nanoreservior. Lactobionic acid (LA) molecules acted as the targeting moiety to achieve the targeted drug delivery. The results of scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET), Barett-Joyner-Halenda (BJH), Fourier transform infrared spectroscopy (FTIR) and zeta potential measurements confirmed the successful preparation of LA-Col-S-S-MHAp step-by-step. Dithiothreitol (DTT) was used as an external stimulus to trigger the redox-responsive release of the drug in order to investigate the controlled release behavior of LA-Col-S-S-MHAp. The result proved that LA-Col-S-S-MHAp nanocomposite has a good end-capping efficiency of the drug under physiological conditions, and it has a characteristic of rapid response and burst drug release when exposed to reducing conditions. Confocal laser scanning microscopy (CLSM) images and flow cytometry assay demonstrated that LA-Col-S-S-MHAp nanoparticles were endocytosed and located in the cytoplasm of cells. Redox-responsive targeted drug delivery could be achieved within cells. The system affords references and ideas for designing novel stimuli responsive nanoreservoir to the clinical therapy of liver cancer.

Enhanced oxidized regenerated cellulose with functionalized multiwalled carbon nanotubes for hemostasis applications

Oxidized Regenerated Cellulose (ORC) has been modified by incorporating aminated MWCNTs (MWCNT-NH2)s. The pristine MWCNTs (pMWCNTs) were aminated which introduced aromatic amine groups on the side walls of the MWCNTs. For modification of neat ORC, the MWCNT-NH2s were reacted with neat ORC. To explore the origin of this behavior, amination of MWCNTs, dispersion of MWCNT-NH2s in the ORC matrix and their interfacial interactions were investigated by SEM, FT-IR and XPS. The analytical results show that during functionalization of the MWCNTs, the amine groups grafted onto the surface of the MWCNTs. In addition, the FT-IR and XPS results revealed that a relatively strong interaction existed between the aminated MWCNTs and the ORC macromolecules. The hydrophilicity test results revealed a significant increment in water uptake of the MWCNT-NH2s/ORC composites with increasing concentration of MWCNT-NH2s in the composites. The haemostatic evaluation of the MWCNT-NH2s/ORC composites in rabbits shows that the aminated MWCNTs increase the rate of blood stopping and hence decrease the blood loss from injured sites.

Processing and characterization of ZnO nanowire-grown PBO fibers with simultaneously enhanced interfacial and atomic oxygen resistance properties

The surface of poly(p-phenylene benzobisoxazole) (PBO) fibers was modified by Zinc oxide nanowires (ZnO NWs) using a mild hydrothermal method to enhance the interfacial properties of PBO fiber/epoxy composites. A functionalization technique was developed to improve the bonding between the PBO fiber and ZnO NWs and was validated by X-ray photoelectron spectroscopy (XPS). Energy dispersive spectrometry (EDS), X-ray diffractometry (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), wettability testing and single fiber tensile testing were performed to characterize the hybrid fibers. The quantitative relationships between the process parameters (solution concentration ratio and growth time), structure and interfacial shear strength (IFSS) of ZnO NW-grown PBO fibers were systematically investigated. Moreover, the possible interfacial property enhancing reasons were explored. Experimental testing showed that the ZnO NWs interphase developed here offered a significant increase in the IFSS (increased by 50.7%) without degrading the base fiber. It was also shown for the first time that dense ZnO NWs could serve as barriers to protect the PBO fiber underneath from atomic oxygen (AO) erosion, which resulted in their potential applications.

Processing, characterization and hemostatic mechanism of a ultraporous collagen/ORC biodegradable composite with excellent biological effectiveness

Collagen, one of the most biocompatible materials in nature, is widely used in wound healing and organ repair. However, the limited mechanical strength and biological effectiveness of collagen restrain its application as a hemostasis and filling material in medicine. To overcome these limitations, ultraporous collagen/oxidized regenerated cellulose (Col/ORC) composites were prepared. The results showed that the Col-0.25%ORC composite had optimal wettability, porosity, and water absorption. An MTT assay proved that the Col and Col/ORC composites possessed no cytotoxicity in living cells. Evaluation of the hemostatic time in vivo and the amount of bleeding in two injury models revealed that the Col-0.25%ORC composite has the most outstanding biological effectiveness and could be biodegraded completely without any inflammatory reaction after 3 weeks. The SEM micrographs showed that the fasciculate ORC fibers were evenly dispersed into the reticulate structure of the Col sponge. The FT-IR spectra of the Col-ORC composites were completely different from that of neat ORC, but similar to Col spectra. Moreover, a possible hemostasis mechanism was discussed based on ELISA analysis, coagulation function, and physicochemical properties.

Reinforced collagen with oxidized microcrystalline cellulose shows improved hemostatic effects

Sponges composed of different levels of composite collagen/oxidized microcrystalline cellulose (collagen/OMCC), denoted M1-M4, were studied to improve the hemostatic effect of single-collagen sponges. Surface morphological observations showed that structural combinations and intermolecular interactions occurred between collagen and OMCC in the composites. M2 presented the best physical properties and platelet activation and was thus selected for the investigations of the in vitro coagulation time and hemostatic and biological effects on animals. The results illustrated that M2 could reduce the length of the activated partial thromboplastin time (APTT) and thrombin time (TT) and presented rapid hemostatic efficiency in the two injury models (P<0.05). These findings were used to evaluate the hemostatic mechanism of M2, which can promote blood absorption and platelet activation and could be directly involved in the intrinsic coagulation pathway to accelerate hemostasis. Furthermore, M2 was not cytotoxic and was completely biodegraded in subcutaneous tissue within 28days.

Artificial extracellular matrix delivers TGFb1 regulating myofibroblast differentiation

During wound healing, the contractile activity of myofibroblasts differentiated from fibroblasts in active transforming growth factor β1 (TGFβ1) conditions has vital functions. In wound dressing biomaterials, it is crucial to mimic the extracellular matrix to deliver the right amount of TGFβ1 in a spatiotemporally controlled manner. We report here, for the first time, a zero-order, sustained TGFβ1 release from electrospun biomimetic nanofibers realizing optimal cell viability and myofibroblast differentiation capacity, confirmed by cell metabolic activity CCK assay, gene expression level through real-time PCR and protein expression level through immunochemical staining.

Preparation, functional characterization and hemostatic mechanism discussion for oxidized microcrystalline cellulose and its composites

Effective and affordable hemostatic materials are of great interests in the development of biomaterials. Lignocellulose, which is a raw material for microcrystalline cellulose, is one of the most economical and readily available polymers in the nature. The oxidized microcrystalline cellulose particles prepared in NO2/CCl4 oxidation system may be a type of affordable, effective and nontoxic hemostatic biomaterial. The FT-IR and 13C solid state NMR results showed that the hydroxyl groups on C6 of cellulose were highly selectively oxidized. The increase of carboxyl content and Zeta potential of OMCC were highly dependent on the oxidation time at the first 64 h. XRD spectra indicated that the crystallinity changed from 70.01 % (MCC) to 60.63 % (OMCC-96 h), and the particle size decreased to 80 µm (OMCC-96 h). To composite with oxidized regenerated cellulose gauze, the OMCC-64 h was optimal, based on the dramatically reduced DP value after 64 h oxidization. The results showed this novel composite with negative charge exhibited good hemostatic property and antibacterial activity. The composite was possessed of both the good biocompatibility for mouse endothelial cells in vitro and the superior biodegradation for rabbits in vivo. Moreover, the data of enzyme-linked immunosorbent assay and blood coagulation tests in vitro suggested that the composite could adsorb and activate the platelets, and then the platelet glycoprotein (GPIIb/IIIa) receptor became competent to bind soluble fibrinogen. The composite also greatly accelerated the activation of the blood coagulation factor XII, and promoted the generation of thrombin, so that the extrinsic route of blood coagulation was initiated.

Incorporation of bacteriophages in polycaprolactone/collagen fibers for antibacterial hemostatic dual-function

Effective and affordable, antibacterial and hemostatic materials are of great interests in clinical wound care practices. Herein, Enterobacteria phage T4 were incorporated in polycaprolactone/collagen I (PCL-ColI) nanofibers via electrospinning in order to eradicate Escherichia coli infection and meanwhile establish hemostasis. Tensile strength of the membrane was significantly enhanced with increased PCL ratio. Those with a collagen component above 70% were demonstrated to be more hemostatic with shorter hemostatic time and smaller amount of bleeding. On the other hand, the T4 phage incorporated PCL-ColI membrane (PCL:ColI = 30%/70%, w/w) exhibited the optimal antibacterial efficiency (above 90%). The in vivo evaluation indicated that the PCL-ColI B (30%:70%, w/w) membrane fully degraded in 8 weeks and no obvious pathological reaction to muscle and subcutaneous layer tissues in the back of rabbit was found. The novel fibrous hemostatic materials coupled with phage therapy hold great promise in designing novel antibacterial, hemostatic wound dressings that addresses concerns of antibiotic resistance.