Stimuli-responsive nanocomposite: potential injectable embolization agent.

Liver cancer remains a significant medical problem and one promising therapeutic approach is to embolize the tumor. One emerging embolization strategy is to use thermoresponsive materials that can be injected but gel at the tumor site. It is now reported on thermoresponsive nanocomposites generated by grafting poly(N-isopropylacrylamide) chains on bacterial cellulose nanowhiskers. Chemical and physical evidences are provided for grafting and demonstrated a sol-gel transition when the temperature is increased above 34.3 °C. Cytotoxicity test in human umbilical vein endothelial cells indicates the excellent biocompatibility of these nanocomposites for use as embolic materials. These results suggest that the nanocomposites offer appropriate properties for embolization of hepatocellular carcinoma.

Long-acting PEGylated growth hormone in children with idiopathic short stature.

Objective: To evaluate the safety and efficacy of weekly PEGylated-recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS) in China. Design and methods: This was a multicenter, phase II study in which all subjects were randomized 1:1:1 to weekly s.c. injections of PEG-rhGH 0.1 (low-dose (LD) group) or 0.2 mg/kg/week (high-dose (HD) group) or control for 52 weeks. The primary end point was change (Δ) in height s.d. score (HT-SDS) from baseline to week 52. Secondary end points were height velocity (HV), bone maturity, insulin-like growth factor-1 (IGF-1) SDS, and IGF-1/insulin-like growth factor-binding protein-3 (IGFBP-3) molar ratio. Results: A total of 360 children with ISS were recruited in the study (n = 120 in each group). At week 52, ΔHT-SDS was 0.56 ± 0.26, 0.98 ± 0.35, and 0.20 ± 0.26 in the LD, HD, and control groups, respectively (within-group P < 0.0001; intergroup P < 0.0001). Statistically significant values of ΔHV, IGF-1, IGF-1/IGFBP-3 ratio, and IGF-1 SDS at week 52 from baseline were observed in both treatment groups (P < 0.0001). There were clear dose-dependent responses for all auxological variables. PEG-rhGH was well tolerated throughout the treatment period with treatment-emergent adverse events (TEAEs) reported in 86.5%, 84.6%, and 91.3% of children in the HD, LD, and control groups, respectively. The incidence of TEAEs was similar in all treatment groups despite the difference in doses. A total of 27 (8.7%) children experienced drug-related TEAEs. Conclusion: Fifty-two-week treatment with PEG-rhGH 0.1 or 0.2 mg/kg/week achieved significant improvement in HT-SDS and other growth-related variables, including HV, IGF-1 SDS, and IGF-1/IGFBP-3 ratio, in a dose-dependent manner. Both doses were well tolerated with similar safety profiles.

Liposomes Encapsulating Neoantigens and Black Phosphorus Quantum Dots for Enhancing Photothermal Immunotherapy.

Colorectal cancer frustrates with high relapse after the traditional treatment including surgery and chemotherapy. Neoantigen-based therapeutic vaccine has achieved high response rate in the clinical trials rising the immunotherapy as a promising alternative for colorectal cancer. Herein, colon cancer cells derived neoantigen peptide Adpgk were employed to be co-encapsulated with black phosphorus quantum dots into liposome (Adpgk-BPQDs-liposome) as therapeutic vaccine. Adpgk-BPQDs-liposome were dispersed in F127 gel containing GM-CSF. The heat generated by black phosphorus (BP) under 808 nm near-infrared laser irradiation accelerates the F127 gel ablation and the release of GM-CSF, which recruit APC cells and prime the native T cells. The tumor bearing mice received the programmed cell death protein 1 (PD-1) checkpoint blockade antibody combined with photo-thermal gel intensively prevented the tumor progress. Furthermore, the tumor infiltrating CD8+ T cells were significantly increased which lead to the elimination of the tumor.

Preparation of chitosan-collagen-alginate composite dressing and its promoting effects on wound healing.

The present study aimed to prepare a composite dressing composed of collagen, chitosan, and alginate, which may promote wound healing and prevent from seawater immersion. Chitosan-collagen-alginate (CCA) cushion was prepared by paintcoat and freeze-drying, and it was attached to a polyurethane to compose CCA composite dressing. The swelling, porosity, degradation, and mechanical properties of CCA cushion were evaluated. The effects on wound healing and seawater prevention of CCA composite dressing were tested by rat wound model. Preliminary biosecurity was tested by cytotoxicity and hemocompatibility. The results revealed that CCA cushion had good water absorption and mechanical properties. A higher wound healing ratio was observed in CCA composite dressing treated rats than in gauze or chitosan treated ones. On the fifth day, the healing rates of CCA composite dressing, gauze, and chitosan were 48.49%±1.07%, 28.02%±6.4%, and 38.97%±8.53%, respectively. More fibroblast and intact re-epithelialization were observed in histological images of CCA composite dressing treated rats, and the expressions of EGF, bFGF, TGF-ß, and CD31 increased significantly. CCA composite dressing showed no significant cytotoxicity, and favorable hemocompatibility. These results suggested that CCA composite dressing could prevent against seawater immersion and promote wound healing while having a good biosecurity.

Double network bacterial cellulose hydrogel to build a biology-device interface.

Establishing a biology-device interface might enable the interaction between microelectronics and biotechnology. In this study, electroactive hydrogels have been produced using bacterial cellulose (BC) and conducting polymer (CP) deposited on the BC hydrogel surface to cover the BC fibers. The structures of these composites thus have double networks, one of which is a layer of electroactive hydrogels combined with BC and CP. The electroconductivity provides the composites with capabilities for voltage and current response, and the BC hydrogel layer provides good biocompatibility, biodegradability, bioadhesion and mass transport properties. Such a system might allow selective biological functions such as molecular recognition and specific catalysis and also for probing the detailed genetic and molecular mechanisms of life. A BC-CP composite hydrogel could then lead to a biology-device interface. Cyclic voltammetry and electrochemical impedance spectroscopy (EIS) are used here to study the composite hydrogels' electroactive property. BC-PAni and BC-PPy respond to voltage changes. This provides a mechanism to amplify electrochemical signals for analysis or detection. BC hydrogels were found to be able to support the growth, spreading and migration of human normal skin fibroblasts without causing any cytotoxic effect on the cells in the cell culture. These double network BC-CP hydrogels are biphasic Janus hydrogels which integrate electroactivity with biocompatibility, and might provide a biology-device interface to produce implantable devices for personalized and regenerative medicine.