Mussel-inspired and aromatic disulfide-mediated polyurea-urethane with rapid self-healing performance and water-resistance.

Although lots of methods have been developed for self-healing materials, it remains a formidable challenge to achieve a thermosetting material with water-insensitive and self-healing properties at room temperature. Nature always provides intelligent strategies for developing advanced materials with superior properties. Herein, a novel self-healable polyurea-urethane was rationally designed by combining mussel adhesive protein-mimetic structure and dynamic aromatic disulfide bonds. It achieves high self-healing efficiency of 98.4% at room temperature for only 6 h and 90% at 60℃ for only 30 min without any external stimuli. Impressively, this self-healing capability possesses exceptional water-resistance, which presents high self-healing efficiency of 98.1% for 2 h and 82.1% for 6 h in 60℃ and 25℃ water, respectively. Besides, the designed polyurea-urethane exhibits excellent mechanical properties such as high elongation at break of 2400%, notch-insensitive stretching elongation of 1500% and notable recovery capability. This strategy shows promising application potential in solid propellants, protective coating, electronic skin, soft sensors and other water-resistant devices.

Bioinspired modified graphene oxide/polyurethane composites with rapid self-healing performance and excellent mechanical properties.

Self-healing efficiency and mechanical strength are always a pair of mechanical contradictions of a polymer. Herein, a series of novel mussel-inspired modified graphene oxide/polyurethane composites were successfully fabricated via rational molecular design and introducing hyperbranched polymer-modified graphene oxide. The composites exhibit outstanding self-healing performances with a self-healing efficiency of 87.9%. Especially, their self-healing properties possess exceptional water-insensitivity, which presents a high self-healing efficiency of 92.5% under 60 °C water for 2 h and 74.6% under 25 °C water for 6 h. Furthermore, the tensile strength of the composites increased by 107.7% with a high strain of 2170%. In addition, the composites show a remarkable recovery capability of 76.3% and 83.7% under tensile and compression loading, respectively, after 20 cycles. This strategy shows prominent application potential in high-performance solid propellants, protective coating, electronic skin, soft sensors and other water-insensitive devices.

Hyperbranched polyamide modified graphene oxide-reinforced polyurethane nanocomposites with enhanced mechanical properties.

As is well known, it is difficult to simultaneously improve both the strength and elongation at break of polymers filled with nanomaterials. This work obtained high-performance composites with enhanced strength and elongation at break via cross-linking hydroxyl-terminated polybutadiene (HTPB) chains with hyperbranched-polyamide-modified graphene oxide (HGO), and the preparation, characterization, and mechanical properties of the composites serving as a composite solid-propellant binder have been described in detail. Compared with pure HTPB polyurethane (P-HTPB), the tensile strength and elastic modulus of the composite containing 0.1 wt% HGO (H-0.1/HTPB) increase by 57.8% and 65.3%, respectively. Notably, the elongation at break of the H-0.1/HTPB composite can reach up to 1292.6%, which is even higher than that of P-HTPB. Moreover, the capabilities of the composites to resist deformation have also been enhanced significantly. The glass transition temperatures of the composites are still extremely low (∼-73 °C), which is beneficial for their applications. It can be expected that this study can provide an effective fabrication approach and strategy for preparing high-performance polyurethane composites.

Biodegradable Hypericin-Containing Nanoparticles for Necrosis Targeting and Fluorescence Imaging.

Necrosis targeting and imaging has significant implications for evaluating tumor growth, therapeutic response, and delivery of therapeutics to perinecrotic tumor zones. Hypericin is a hydrophobic molecule with high necrosis affinity and fluorescence imaging properties. To date, the safe and effective delivery of hypericin to areas of necrosis in vivo remains a challenge because of its incompatible biophysical properties. To address this issue, we have developed a biodegradable nanoparticle (Hyp-NP) for delivery of hypericin to tumors for necrosis targeting and fluorescence imaging. The nanoparticle was developed using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) and hypericin by a modified solvent evaporation technique. The size of Hyp-NP was 19.0 ± 1.8 nm from cryo-TEM and 37.3 ± 0.7 nm from dynamic light-scattering analysis with a polydispersity index of 0.15 ± 0.01. The encapsulation efficiency of hypericin was 95.05% w/w by UV-vis absorption. After storage for 30 days, 91.4% hypericin was retained in Hyp-NP with nearly no change in hydrodynamic size, representing nanoparticle stability. In an ovarian cancer cell line, Hyp-NP demonstrated cellular internalization with intracellular cytoplasmic localization and preserved fluorescence and necrosis affinity. In a mouse subcutaneous tumor model, tumor accumulation was noted at 8 h postinjection, with near-complete clearance at 96 h postinjection. Hyp-NP was shown to be tightly localized within necrotic tumor zones. Histological analysis of harvested organs demonstrated no gross abnormalities, and in vitro, no hemolysis was observed. This proof-of-concept study demonstrates the potential clinical applications of Hyp-NP for necrosis targeting.

Influence of Thermally-Accelerated Aging on the Dynamic Mechanical Properties of HTPB Coating and Crosslinking Density-Modified Model for the Payne Effect.

Hydroxyl terminated polybutadiene (HTPB) coating is widely used in a solid rocket motor, but an aging phenomenon exists during long-term storage, which causes irreversible damage to the performance of this HTPB coating. In order to study the effect of aging on the dynamic mechanical properties of the HTPB coating, the thermally-accelerated aging test was carried out. The variation of maximum elongation and crosslinking density with aging time was obtained, and a good linear relationship between maximum elongation and crosslinking density was found by correlation analysis. The changing regularity of dynamic mechanical properties with aging time was analyzed. It was found that with the increase of aging time, Tg of HTPB coating increased, Tα, tan ß and tan α decreased, and the functional relationships between the loss factor parameters and crosslinking density were constructed. The storage modulus and loss modulus of HTPB coating increased with the increase of aging time, and decreased with the increase of pre-strain. The aging enhanced the Payne effect of HTPB coating, while the pre-strain had a weakening effect. In view of the Payne effect of HTPB coating, the crosslinking density was introduced into Kraus model as aging evaluation parameter, and the crosslinking density modified models with and without pre-strain were established. The proposed models can effectively solve the problem that the Kraus model has a poor fitting effect under the condition of small strain (generally less than 1%) and on the loss modulus, which have improved the correlations between the fitting results and the test results.

Expression and regulatory effects of microRNA-182 in osteosarcoma cells: A pilot study.

The aim of the present study was to evaluate the expression level of microRNA-182 (miRNA-182) in human osteosarcoma (OS) MG-63 cells and OS tissues, and to elucidate the effect of miRNA-182 on the biological activity of tumors. In the present study, the expression of miRNA-182 in human OS MG-63 cells, OS tissues and normal osteoblast hFOB1.19 cells was determined using quantitative polymerase chain reaction. Subsequently, a miRNA-182 mimic and inhibitor were utilized to regulate the expression level of this miRNA in MG-63 cells. Cell viability and proliferation were examined using cell counting kit-8 assays, and cell apoptosis was detected by flow cytometry. Cell invasion and migration assays were performed using Transwell chambers to analyze the biological functions of miRNA-182 in vitro. The present study demonstrated that the expression level of miRNA-182 in MG-63 cells and OS tissues was significantly increased compared with the hFOB1.19 cell line (P<0.05). The present study successfully performed cell transfections of miRNA-182 inhibitor and miRNA-182 mimic into MG-63 cells and achieved the desired transfection efficiency. The present study confirmed that upregulation of miRNA-182 promotes cell apoptosis and inhibits cell viability, proliferation, invasion and migration. The present findings additionally demonstrated that miRNA-182 is a tumor suppressor gene in OS. Therefore, regulating the expression of miRNA-182 may affect the biological behavior of OS cells, which suggests a potential role for miRNA-182 in molecular therapy for malignant tumors.

Magnetic Resonance Imaging of Postoperative Fracture Healing Process without Metal Artifact: A Preliminary Report of a Novel Animal Model.

Background. Early radiological diagnosis and continual monitoring are of ultimate importance for timely treatment of delayed union, nonunion, and infection after bone fracture surgery. Although magnetic resonance imaging (MRI) could provide superior detailed images compared with X-ray and computed tomography (CT) without ionizing radiation, metal implants used for fracture fixation lead to abundant artifacts on MRI and thus prohibit accurate interpretation. The authors develop a novel intramedullary fixation model of rat femoral fracture using polyetheretherketone (PEEK) threaded rods and investigate its feasibility for in vivo MRI monitoring of the fracture healing process without artifact. Methods. Femoral fractures of 3 adult male Sprague-Dawley rats were fixed with intramedullary PEEK threaded rods. X-ray and MRI examinations were performed at day 7 postoperatively. Radiological images were analyzed for the existence of artifact interruption and postoperative changes in bone and peripheral soft tissue. Results. Postoperative plain film revealed no loss of reduction. MRI images illustrated the whole length of femur and peripheral tissue without artifact interruption, and the cortical bone, implanted PEEK rod, and soft tissue were clearly illustrated. Conclusion. This preliminary study introduced a novel rat model for in vivo MRI monitoring of the fracture healing process without metal artifact, by using intramedullary fixation of femur with PEEK threaded rod.

Morphologic changes within the cerebellar cortex in the unilateral 6-hydroxydopamine lesioned rat model for Parkinson disease.

Parkinson's disease (PD) is a common neurodegenerative disorder caused by the progressive loss of dopaminergic neurons in the substantia nigra. Most investigations have focused on the cerebral regions such as the basal ganglia, thalamus, or the substantia nigra, but whether there is pathologic impairment within the cerebellum has rarely been assessed. Synapsin and neurofilament as the inner markers of neurons and synapses reflect the functional state by their distribution or expression. Significant morphologic changes at the cellular level have been demonstrated directly or indirectly in multiple neurodegenerative diseases. The purpose of this study was to determine whether the behavioral abnormalities that accompany PD are associated with the cerebellum using an in vivo 6-hydroxydopamine lesioned rat model. Forty-two rats were divided into three groups, the Parkinsonian group (N=22), sham group (N=10) and control group (N=10). The dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylase-immunopositive cells. Immunohistochemical studies showed that the density of synapsin I in the granular layer of the cerebellum on both sides of the Parkinsonian -model was not statistically significantly different compared to the control and sham groups. However, expression of neurofilament H in the cortex within bilateral paramedian lobule (PML) and Crus 2 of the ansiform lobule (C2AL) in cerebellum posterior lobe of Parkinsonian rats was decreased compared with controls (P<0.05), especially in the loss of Purkinje cells and the presence of morphologic abnormalities in the cell nucleus. The study suggested that loss of neurons and synapses may take place in the cerebellar cortex of Parkinson's disease, and might play an important role in the pathologic mechanism of PD.

A Novel Rat Model of Intramedullary Tibia Fracture Fixation Using Polyetheretherketone Threaded Rod.

BACKGROUND: The rat fracture fixation models have been widely adopted, but current implant designs suffer from operational difficulty, massive soft-tissue dissection, and radiological intervention. The authors developed a new tibia fracture-healing model using minor invasive intramedullary fixations with polyetheretherketone (PEEK) threaded rods, which have excellent x-ray translucency and no magnetic resonance artifact. METHODS: Tibia fractures of 6 adult male Sprague-Dawley rats were fixed with intramedullary PEEK threaded rods. X-ray examination was performed at 0, 4, and 8 weeks postoperatively. Histological analysis was conducted via hematoxylin-eosin staining of nondecalcified tissue sections. RESULTS: Radiological fracture healing was observed at 8 weeks postoperatively. Histology demonstrated fracture gap bridging and bone ingrowth adjacent to PEEK. CONCLUSION: This innovative model is simple and effective, providing a new selection in future biomedical research.

(2-Hydroxypropyl)-ß-Cyclodextrin Is a New Angiogenic Molecule for Therapeutic Angiogenesis.

BACKGROUND: Peripheral artery disease (PAD), which is caused by atherosclerosis, results in progressive narrowing and occlusion of the peripheral arteries and inhibits blood flow to the lower extremities. Therapeutic angiogenesis is a promising strategy for treating ischemia caused by PAD. Nitric oxide (NO) has been shown to be a key mediator of angiogenesis. It has been demonstrated that ß-cyclodextrincan stimulate vessel growth in rabbit corneas. In this study, we assessed the mechanism of action and therapeutic potential of a new angiogenic molecule, (2-hydroxypropyl)-ß-cyclodextrin (2HP-ß-CD). METHODS AND RESULTS: 2HP-ß-CD significantly increased vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor BB (PDGF-BB) peptides in human umbilical vein endothelial cells (HUVECs) and also increased basic fibroblast growth factor (bFGF) peptide in human aortic smooth muscle cells (HASMCs). 2HP-ß-CD stimulated both proliferation and migration of HUVECs in an endothelial nitric oxide synthase (eNOS)/NO-dependent manner, whereas NO was found to be involved in proliferation, but not migration, of HASMCs. In a unilateral hindlimb ischemia model in mice, 2HP-ß-CD injections not only promoted blood flow recovery and increased microvessel densities in ischemic muscle, but also promoted coverage of the vessels with smooth muscle cells, thus stabilizing the vessels. Administration of 2HP-ß-CD increased the expression of several angiogenic factors, including VEGF-A, PDGF-BB and transforming growth factor beta-1 (TGF-ß1) in ischemic muscle. Injections of 2HP-ß-CD also stimulated protein kinase B and extracellular regulated protein kinases (ERK), leading to an increase in phosphorylation of eNOS in ischemic muscle. Treatment with the NOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), showed that stimulation of blood flow induced by 2HP-ß-CD was partially dependent on NO. CONCLUSIONS: Therapeutic angiogenesis by 2HP-ß-CD may be beneficial to patients with PAD.

Surgical Modification of the Murine Calvaria Osteolysis Model.

The murine calvaria model has been adopted for evaluation of osteolysis and inflammation induced by polyethylene (PE) or metal wear debris. However, this model suffers from several complications. The purpose of our study is to introduce a surgical modification with lower complication rates, thus providing more accurate results. Forty C57/BL6 mice were divided into two groups, both receiving polyethylene particles. Surgical modifications were performed in group 1, and group 2 underwent traditional surgeries. The incidence of fluid leakage was recorded on the operative day. Curst formation, wound dehiscence, and bone exposure were recorded on day 7. Histological osteolysis was demonstrated by HE staining of tissue slices. Micro-CT was used for quantifying evaluation of osteolysis in two groups. Intraoperative fluid leakage was significantly reduced in group 1. Postoperative crust formation, wound dehiscence, and bone exposure were also significantly decreased in group 1. HE staining results revealed obvious osteolysis in group 1 and more obvious osteolysis in group 2. Bone volume fraction (BVF) was (0.32 ± 0.03) in group 1 compared to group 2 (0.24 ± 0.05). Bone mineral density (BMD) was (1.11 ± 0.03) in group 1 compared to group 2 (1.01 ± 0.02). Surgical modifications provide a reliable way for establishment of the murine calvaria osteolysis model.

Low intensity ultrasound promotes the sensitivity of rat brain glioma to Doxorubicin by down-regulating the expressions of p-glucoprotein and multidrug resistance protein 1 in vitro and in vivo.

The overall prognosis for malignant glioma is extremely poor, and treatment options are limited in part because of multidrug resistant proteins. Our previous findings suggest low intensity ultrasound (LIUS) can induce apoptosis of glioma cells. Given this finding, we were interested in determining if LIUS could help treat glioma by inhibiting multidrug resistant proteins, and if so, which pathways are involved. In this study, the toxicity sensitivity and multidrug resistance proteins of glioma induced by LIUS were investigated using CCK-8, immunohistochemistry, immunofluorency, and RT-PCR in tissue samples and cultured cells. LIUS inhibited increase of C6 cells in an intensity- and time-dependent manner. The toxicity sensitivity of C6 cells increased significantly after LIUS sonication (intensity of 142.0 mW/cm(2)) or Doxorubicin (DOX) at different concentration, particularly by the combination of LIUS sonication and DOX. The expressions of P-gp and MRP1 decreased significantly post-sonication at intensity of 142.0 mW/cm(2) both in vitro and in vivo. The expressions of p110 delta (PI3K), NF-κB-p65, Akt/PKB, and p-Akt/PKB were downregulated by LIUS sonication and DOX treatment separately or in combination at the same parameters in rat glioma. These results indicate that LIUS could increase the toxicity sensitivity of glioma by down-regulating the expressions of P-gp and MRP1, which might be mediated by the PI3K/Akt/NF-κB pathway.