•We introduced a silk fibroin (SF)-based neurobridge as scaffold enriched with/without nerve growth factor (NGF).•NGF released from alginate (Alg) microspheres on SF scaffold to the central lesion site of SCI.•The sparing of spinal cord tissue and the number of surviving neurons were increased.•This optimal multi-disciplinary approach offers a promising treatment for the injured spinal cord.Neurons loss and axons degeneration after spinal cord injury (SCI) gradually give rise to result in functional motor and sensory impairment. A bridging biomaterial scaffold that allows the axons to grow through has been investigated for the repair of injured spinal cord. In this study, we introduced a silk fibroin (SF)-based neurobridge as scaffold enriched with/without nerve growth factor (NGF) that can be utilized as a therapeutic approach for spinal cord repair. NGF released from alginate (Alg) microspheres on SF scaffold (SF/Alg composites scaffolds) to the central lesion site of SCI significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons. This optimal multi-disciplinary approach of combining biomaterials, controlled-release microspheres and neurotrophic factors offers a promising treatment for the injured spinal cord.Download high-res image (329KB)Download full-size image

•Polyethyleneimine-grafted carboxymethyl chitosan (CMCS–PEI) were synthesised.•The CMCS–PEI copolymer showed lower cytotoxicity and higher transfection efficiency.•The haemocompatibility of the CMCS–PEI copolymer was investigated.•CMCS–PEI copolymer had little impact on the aggregation, morphology or lysis of RBCs, or on blood coagulation.The development of safe and efficient gene carriers is the key to the clinical success of gene therapy. In the present study, carboxymethyl chitosan (CMCS) was prepared by chitosan (CS) alkalisation and carboxymethylation reactions. Then polyethyleneimine (PEI) was grafted to the backbone of CMCS by an amidation reaction. The CMCS–PEI copolymer showed strong complexation capability with DNA to form nanoparticles, and achieved lower cytotoxicity and higher transfection efficiency compared with PEI (25 kDa) towards 293T and 3T3 cells. Moreover, the haemocompatibility of the CMCS–PEI copolymer was investigated through the aggregation, morphology and lysis of human red blood cells (RBCs), along with the impact on the clotting function with activated partial thromboplastin time (APTT), prothrombin time (PT) and thromboelastographic (TEG) assays. The results demonstrated that the CMCS–PEI copolymer with a concentration lower than 0.05 mg/mL had little impact on the aggregation, morphology or lysis of RBCs, or on blood coagulation. Therefore, the copolymer may be a strong alternative candidate as an effective and safe non-viral vector.

Carboxyl single-walled carbon nanotubes (SWNTs) were used to construct an innovative drug delivery system by modification with chitosan (CHI) to enhance water solubility and biocompatibility. Hyaluronan (HA), as the target ligand for CD44, was bound to the CHI layer to selectively kill cancer cells. To achieve a new treatment strategy for cancer, the drug delivery system was loaded with the anticancer drug doxorubicin hydrochloride (DOX). The data showed that the system loaded with DOX with zeta potentials of 8.52 ± 0.12 mV at pH 7.4 and 12.53 ± 0.23 mV at pH 5.5 had high drug-loading efficiency, reaching 107.73 ± 0.67%. It also exhibited sustained and controlled drug-release, depending on pH; it released less than 10% at pH 7.4 but nearly 85% at pH 5.5 after 72 h. Cell viability results indicated that the drug delivery system effectively killed HeLa cells while it had lower cytotoxicity against fibroblasts. Combined histological examinations and blood property analyses demonstrated that it did not cause severe damage to vital organs in SD rats. Thus, this drug delivery system may provide a high therapeutic efficacy for cancer, while minimising adverse side effects.

•PLGA and PLGA/CNC composite nanofiber membranes were prepared.•Morphology, thermodynamic and mechanical properties of nanofiber membranes were characterized.•Cytocompatibility and cellular responses of nanofiber membranes were studied.•PLGA/CNC composite nanofiber membranes had better cytocompatibility.Although extensively used in the fields of drug-carrier and tissue engineering, the biocompatibility and mechanical properties of polylactide–polyglycolide (PLGA) nanofiber membranes still limit their applications. The objective of this study was to improve their utility by introducing cellulose nanocrystals (CNCs) into PLGA nanofiber membranes. PLGA and PLGA/CNC composite nanofiber membranes were prepared via electrospinning, and the morphology and thermodynamic and mechanical properties of these nanofiber membranes were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). The cytocompatibility and cellular responses of the nanofiber membranes were also studied by WST-1 assay, SEM, and confocal laser scanning microscopy (CLSM). Incorporation of CNCs (1, 3, 5, and 7 wt.%) increased the average fiber diameter of the prepared nanofiber membranes from 100 nm (neat PLGA) to ∼400 nm (PLGA/7 wt.% CNC) and improved the thermal stability of the nanofiber membranes. Among the PLGA/CNC composite nanofiber membranes, those loaded with 7 wt.% CNC nanofiber membranes had the best mechanical properties, which were similar to those of human skin. Cell culture results showed that the PLGA/CNC composite nanofiber membranes had better cytocompatibility and facilitated fibroblast adhesion, spreading, and proliferation compared with neat PLGA nanofiber membranes. These preliminary results suggest that PLGA/CNC composite nanofiber membranes are promising new materials for the field of skin tissue engineering.

Chitosan (CS) was first modified hydrophobically with deoxycholic acid (DCA) and then with polyethylene glycol (PEG) to obtain a novel amphiphilic polymer (CS–DCA–PEG). This was covalently bound to folic acid (FA) to develop nanoparticles (CS–DCA–PEG–FA) with tumor cell targeting property. The structure of the conjugates was characterised using Fourier transform infrared and 1H nuclear magnetic resonance spectroscopy and X-ray diffraction. Based on self-aggregation, the conjugates formed nanoparticles with a low critical aggregation concentration of 0.035 mg/ml. The anti-cancer drug doxorubicin (DOX) was encapsulated into the nanoparticles with a drug-loading capacity of 30.2 wt%. The mean diameter of the DOX-loaded nanoparticles was about 200 nm, with a narrow size distribution. Transmission electron microscopy images showed that the DOX-loaded nanoparticles were spherical. The drug release was studied under different conditions. Furthermore, the cytotoxic activities of DOX in CS–DCA–PEG–FA nanoparticles against folate receptor (FR)-positive HeLa cells and FR-negative fibroblast 3T3 cells were evaluated. These results suggested that the CS–DCA–PEG–FA nanoparticles may be a promising vehicle for the targeting anticancer drug to tumor cells.

Alzheimer disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence extracellular neuritic plaques and with a large number of neurons lost. In this paper, we design a new nanomaterial, graphene quantum dots (GQDs) conjugated neuroprotective peptide glycine-proline-glutamate (GQDG) and administer it to APP/PS1 transgenic mice. The in vitro assays including ThT and CD proved that GQDs and GQDG could inhibit the aggregation of Aβ1-42 fibrils. Morris water maze was performed to exanimate learning and memory capacity of APP/PS1 transgenic mice. The surface area of Aβ plaque deposits reduced in the GQDG group compared to the Tg Ctrl groups. Furthermore, newly generated neuronal precursor cell and neuron were test by immunohistochemical. Besides, neurons were impregnated by DiI using gene gun to show dendritic spine. Results indicated enhancement of learning and memory capacity and increased amounts of dendritic spine were observed. Inflammation factors and amyloid-β (Aβ) were tested with suspension array and ELISA, respectively. Several pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-33, IL-17α, MIP-1β and TNF-α) had decreased in GQDG group compared with Control group. Reversely, anti-inflammatory cytokines (IL-4, IL-10) had increased in GQDG group compared with Control group. Thus, we demonstrate that the GQDG is a promising drug in treatment of neurodegenerative diseases such as AD.

•SF/AGs/GDNF scaffolds seeded with hUCMSCs were prepared.•SF/AGs/GDNF scaffold had the best sustained and controlled release of GDNF.•GDNF and stem cells could form the micro-environment of growth and repair of the neurons.•The composite scaffolds exhibited better therapeutic and repair effects to the SCI.Spinal cord injury (SCI) is a severe trauma for which no effective treatment is currently available. In this study, a composited treatment system was prepared using a silk fibroin/alginates/glial cell line-derived neurotrophic factor (SF/AGs/GDNF) scaffold seeded with human umbilical cord mesenchymal stem cells (hUCMSCs) and the combined therapeutic effects of the composite scaffold to repair SCI rats were evaluated. The use of SF as a scaffold material could act as a biomimetic platform allowing neurons to properly accommodate and rebuild the target tissue. The SF/AGs/GDNF scaffold had the best sustained-release function and the AGs were the key determining factor in the controlled release of GDNF. After 8 weeks of treatment, the hUCMSCs on SF/AGs/GDNF composite scaffolds could significantly enhance the scar expansion of spinal cord tissue and increased the number of surviving neurons. The combination of GDNF and hUCMSCs transplantation loaded on SF/AGs composite scaffolds exhibited better therapeutic and repair effects to the SCI of rats, compared with the SF/AGs group or GDNF alone on SF/AGs scaffolds. The composite scaffold, GDNF and stem cells could build a bioactive material to form the micro-environment of growth and repair of the neurons. These results may provide a theoretical basis and beneficial exploration for clinical treatment of SCI.

Carboxyl single-walled carbon nanotubes (SWNTs) were used to construct an innovative drug delivery system by modification with chitosan (CHI) to enhance water solubility and biocompatibility. Hyaluronan (HA), as the target ligand for CD44, was bound to the CHI layer to selectively kill cancer cells. To achieve a new treatment strategy for cancer, the drug delivery system was loaded with the anticancer drug doxorubicin hydrochloride (DOX). The data showed that the system loaded with DOX with zeta potentials of 8.52 ± 0.12 mV at pH 7.4 and 12.53 ± 0.23 mV at pH 5.5 had high drug-loading efficiency, reaching 107.73 ± 0.67%. It also exhibited sustained and controlled drug-release, depending on pH; it released less than 10% at pH 7.4 but nearly 85% at pH 5.5 after 72 h. Cell viability results indicated that the drug delivery system effectively killed HeLa cells while it had lower cytotoxicity against fibroblasts. Combined histological examinations and blood property analyses demonstrated that it did not cause severe damage to vital organs in SD rats. Thus, this drug delivery system may provide a high therapeutic efficacy for cancer, while minimising adverse side effects.