Feathery Tellurium-Selenium Heterostructural Nanoadjuvant for the Synergistic Treatment of Bacterial Infections.

Antibacterial nanoagents with well-controlled structures are greatly desired to address the challenges of bacterial infections. In this study, a featherlike tellurium-selenium heterostructural nanoadjuvant (TeSe HNDs) was created. TeSe HNDs produced 1O2 and had high photothermal conversion efficiency when stimulated with 808 nm near-infrared (NIR) light. To create a synergistic treatment system (TeSe-ICG) with better photothermal and photodynamic capabilities, the photosensitizer indocyanine green (ICG) was then added. With a bactericidal rate of more than 99%, the NIR-mediated TeSe-ICG demonstrated an efficient bactericidal action against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). In addition, TeSe-ICG was also effective in treating wound infections and could effectively promote wound healing without obvious toxic side effects. In conclusion, TeSe-ICG is expected to be a good candidate for the treatment of bacterial infections.

Inorganic nanomaterials for intelligent photothermal antibacterial applications.

Antibiotics are currently the main therapeutic agent for bacterial infections, but they have led to bacterial resistance, which has become a worldwide problem that needs to be addressed. The emergence of inorganic nanomaterials provides a new opportunity for the prevention and treatment of bacterial infection. With the continuous development of nanoscience, more and more inorganic nanomaterials have been used to treat bacterial infections. However, single inorganic nanoparticles (NPs) are often faced with problems such as large dosage, strong toxic and side effects, poor therapeutic effect and so on, so the combination of inorganic nano-materials and photothermal therapy (PTT) has become a promising treatment. PTT effectively avoids the problem of bacterial drug resistance, and can also reduce the dosage of inorganic nanomaterials to a certain extent, greatly improving the antibacterial effect. In this paper, we summarize several common synthesis methods of inorganic nanomaterials, and discuss the advantages and disadvantages of several typical inorganic nanomaterials which can be used in photothermal treatment of bacterial infection, such as precious metal-based nanomaterials, metal-based nanomaterials and carbon-based nanomaterials. In addition, we also analyze the future development trend of the remaining problems. We hope that these discussions will be helpful to the future research of near-infrared (NIR) photothermal conversion inorganic nanomaterials.

Synergistically Promoting Bone Regeneration by Icariin-Incorporated Porous Microcarriers and Decellularized Extracellular Matrix Derived From Bone Marrow Mesenchymal Stem Cells.

Multifunctionality has becoming essential for bone tissue engineering materials, such as drug release. In this study, icariin (ICA)-incorporated poly(glycolide-co-caprolactone) (PGCL) porous microcarriers were fabricated and then coated with decellularized extracellular matrix (dECM) which was derived from bone marrow mesenchymal stem cells (BMSC). The porous structure was generated due to the soluble gelatin within the microcarriers. The initial released ICA in microcarriers regulated osteogenic ECM production by BMSCs during ECM formation. The dECM could further synergistically enhance the migration and osteogenic differentiation of BMSCs together with ICA as indicated by the transwell migration assay, ALP and ARS staining, as well as gene and protein expression. Furthermore, in vivo results also showed that dECM and ICA exhibited excellent synergistic effects in repairing rat calvarial defects. These findings suggest that the porous microcarriers loaded with ICA and dECM coatings have great potential in the field of bone tissue engineering.

A micropatterned conductive electrospun nanofiber mesh combined with electrical stimulation for synergistically enhancing differentiation of rat neural stem cells.

An effective treatment for spinal cord injury (SCI) remains a severe clinical challenge due to the intrinsically limited regenerative capacity and complex anatomical structure of the spinal cord. The combination of biomaterials, which serve as scaffolds for axonal growth, cells and neurotrophic factors, is an excellent candidate for spinal cord regeneration. Herein, a new micropatterned conductive electrospun nanofiber mesh was constructed with poly{[aniline tetramer methacrylamide]-co-[dopamine methacrylamide]-co-[poly(ethylene glycol) methyl ether methacrylate]}/PCL (PCAT) using a rotation electrospinning technology. The aim was to study the synergistic effects of electrical stimulation (ES) and a micropatterned conductive electrospun nanofiber mesh incorporated with nerve growth factor (NGF) on the differentiation of rat nerve stem cells (NSCs). The hydrophilicity of the conductive nanofiber mesh could be tailored by changing the dopamine (DA) and aniline tetramer (AT) content from 19° to 79°. A favorable electroactivity and conductivity was achieved by the AT segment of PCAT. The as-fabricated micropatterned electrospun nanofiber mesh possessed a regularly aligned valley and ridge structure, and the diameter of the nanofiber was 312 ± 58 nm, while the width of the valley and ridge was measured to be 210 ± 17 µm and 200 ± 16 µm, respectively. The growth and neurite outgrowth of differentiated NSCs were observed along the valley of the micropatterned nanofiber mesh. In addition, the NGF loaded micropatterned conductive electrospun nanofiber mesh combined with ES exhibited the highest cell viability, and effectively facilitated the differentiation of NSCs into neurons and suppressed the formation of astrocytes, thus exhibiting a great application potential for nerve tissue engineering.

Mussel-Inspired Conducting Copolymer with Aniline Tetramer as Intelligent Biological Adhesive for Bone Tissue Engineering.

Electrically conducting polymers have been emerging as intelligent bioactive materials for regulating cell behaviors and bone tissue regeneration. Additionally, poor adhesion between conventional implants and native bone tissue may lead to displacement, local inflammation, and unnecessary secondary surgery. Thus, a conductive bioadhesive with strong adhesion performance provides an effective approach to fulfill fixation and regeneration of comminuted bone fracture. Inspired by mussel chemistry, we designed the conductive copolymers poly{[aniline tetramer methacrylamide]-co-[dopamine methacrylamide]-co-[poly(ethylene glycol) methyl ether methacrylate]} [poly(ATMA-co-DOPAMA-co-PEGMA); AT:conductive aniline tetramer; DOPA:dopamine; PEG:poly(ethylene glycol))] with AT content 3.0, 6.0, and 9.0 mol %, respectively. The adhesive strength of this copolymer was enhanced during tensile process perhaps due to the synergistic effects of H-bonding, π-π interactions, and polymer long-chain entanglement, reaching up to 1.28 MPa with 6 mol % AT. Biological characterizations of preosteoblasts indicated that the bioadhesives exhibited desirable biocompatibility. In addition, the osteogenic differentiation was synergistically enhanced by the conductive substrate and electrical stimulation with a square wave, frequency of 100 Hz, 50% duty cycle, and electrical potential of 500 mV, as indicated by ALP activity, calcium deposition, and expression of osteogenic genes. The ALP activity at 14 days and calcium deposition at 28 days on the 9 mol % AT group were significantly higher than that on PLGA under electrical stimulation. The expression value of OPN for 9 mol % AT group was notably upregulated by 5.9-fold compared with PLGA at 7 days under electrical stimulation. Overall, the conductive polymers with strong adhesion can synergistically upregulate the cellular activity combining with electrical stimulation and might be a promising bioadhesive for orthopedic and dental applications.

Synergistic osteogenesis promoted by magnetically actuated nano-mechanical stimuli.

Functional biomaterials with magnetic properties are considerably useful for regulating cell behavior and promoting bone regeneration. And the combination of such biomaterials with physical environmental cues (such as magnetic fields and mechanical stress) might be more favorable for the regulation of cell function. This study is aimed at investigating the combined effects of magnetically responsive materials and a static magnetic field (SMF) on the osteogenic differentiation of osteoblasts and the potential mechanism involved. In this study, oleic acid modified iron oxide nanoparticles (IO-OA NPs) were utilized to generate homogeneous magnetic nanocomposites with poly(lactide-co-glycolide) (PLGA) used as the base and to enhance the mechanical properties of the composites. In vitro experimental results show that in the presence of an external SMF, cell attachment and osteogenic differentiation were significantly improved using the IO-OA/PLGA composites, as indicated by enhanced alkaline phosphatase (ALP) activity, increased mineralized nodule formation, and upregulated bone-associated gene expression (ALP, OCN, and BMP2), in a dose- and time-dependent manner. Furthermore, the upregulated expression levels of piezo-type mechanosensitive ion channel component 1 (Piezo1), a key receptor for sensing mechanical stimuli, implied that the synergistically enhanced osteogenic differentiation was mainly caused as a result of the mechanical stimuli. Such magnetically actuated mechanical stimuli were induced through the nano-deformation of the magnetic substrate under a SMF, which was directly characterized via in situ scanning using atomic force microscopy (AFM). This study demonstrates that magnetically actuated nano-mechanical stimuli may underpin the synergistic effects of magnetic composites and magnetic stimuli to enhance osteogenic differentiation, and they could form the basis of a potential strategy to accelerate bone formation for bone tissue engineering and regenerative medicine applications.

Electroactive Composite of FeCl3 -Doped P3HT/PLGA with Adjustable Electrical Conductivity for Potential Application in Neural Tissue Engineering.

Conducting polymers (CPs) is one of intelligent biomaterials with the specific properties of reversible redox states, which have a significant effects on the cell behaviors and nerve tissue regeneration. However, the effects of CPs with different electrical conductivity on the behaviors of nerve cells are rarely reported. Therefore, a kind of Poly(3-hexylthiophene) (P3HT) with certain molecular weight is synthesized by Kumada catalyst transfer polymerization (KCTP) method and employed to prepare bioabsorbable and electroactive intelligent composites of Poly(3-hexylthiophene)/Poly(glycolide-lactide) (P3HT/PLGA). FeCl3 doping electroactive membranes with different electrical conductivities are prepared to investigate the cell behaviors. On the substrate with higher electrical conductivity, the proliferation of rat adrenal pheochromocytoma cells (PC12 cells) is significantly promoted and neurite length is increased obviously. In particular, the most significant improvements are the neuron gene expression of Synapsin 1 and microtubule-associated protein 2 (MAP2) by the composites with high conductivity. These results suggest that P3HT/PLGA with suitable electrical conductivity have a positive role in promoting neural growth and differentiation, which is promising for advancing potential application of nerve repair and regeneration.

Microcarriers with Controllable Size via Electrified Liquid Jets and Phase Separation Technique Promote Cell Proliferation and Osteogenic Differentiation.

Differently sized poly(lactic-co-glycolic) microspheres were efficiently prepared with electrified liquid jets and a phase separation technique for a wide range of applications. Higher polymer concentrations tended to form larger microcarriers. Polymer concentration can obviously affect bead or fiber formation resulting beads and fiber morphologies. As the voltage of electrostatic field and the needle size increased, the size of microcarriers decreased remarkably. The most suitable concentration of ethanol in the collecting solution might be lower than 55%. The resulting composite microcarriers have significantly narrow size distribution, controllable sizes, and high cell adhesion, growth, and osteodifferentiation abilities.

Electroactive Nanocomposite Porous Scaffolds of PAPn/op-HA/PLGA Enhance Osteogenesis in Vivo.

The three-dimensional (3D) porous nanocomposite biomimic scaffolds with electroactivity and bioactivity were prepared as bone implants by a freeze-drying method using 1,4-dioxane as a solvent. The multiblock copolymer (PAPn) was synthesized by the condensation polymerization of hydroxyl-capped poly(lactide)(PLA) and carboxyl-capped aniline pentamer (AP), which were introduced as electroactive functional polymers. A bioactive component, hydroxyapatite (HA) grafting l-lactic acid oligomer (op-HA), showed a better interface compatibility with PAPn and poly(lactide-co-glycolide) (PLGA). Honeycomb-like and interconnected porous structures could be obtained as displayed by scanning electron microscopy (SEM). The intramuscular implants showed a good biocompatibility and higher osteogenetic activity by promoting cell ingrowth and collagen fibers forming as indicated by SEM, hematoxylin-eosin (H&E) staining, and Masson's trichrome staining. Implantation for the repair of rabbit radius defects under 5 V at 100 Hz with a 50% duty cycle for 30 min every other day was evaluated, and sheep tibia defects were also carried out. The composite scaffold with 1 wt % PAPn exhibited better behaviors, such as a distinct bone callus, bridging growth, vague borderlines between newly formed bone at the two defect ends, and increased bone density as indicated by radiographic images and micro-computed tomography (Micro-CT) images. Electricity stimulation could significantly accelerate the healing of a fracture. All in all, the stimuli-responsive electroactive nanocomposites showed a potential application in bone tissue engineering.

Porous Scaffolds of Poly(lactic-co-glycolic acid) and Mesoporous Hydroxyapatite Surface Modified by Poly(γ-benzyl-l-glutamate) (PBLG) for in Vivo Bone Repair.

Three-dimensional (3D) composite porous scaffolds containing hydroxyapatite (HA) and polymer matrix showed wide applications in bone repair because of their improved biocompatibility, bioactivity, and mechanical properties in our previous studies. In this work, mesoporous hydroxyapatite (MHA) surface-modified by poly(γ-benzyl-l-glutamate) (PBLG) with different amounts (from 11 to 50 wt %) was synthesized by the in situ ring opening polymerization of γ-benzyl-l-glutamate N-carboxy anhydride (BLG-NCA) and then PBLG-g-MHA/PLGA composite films were prepared to illustrate the biological performance of the composites. Furthermore, porous scaffolds of PBLG-g-MHA/PLGA were fabricated through modified solvent casting/particulate leaching (SC/PL) method to demonstrate the ability of in vivo bone defect repair. In vitro cytological assay indicated that enhanced cell expansion on PBLG-g-MHA/PLGA with 11 wt % PBLG amounts and improved osteogenic differentiation on the composites with 33 and 50 wt % PBLG amounts were achieved. And the porous scaffolds exhibited high porosity and interconnected pores. Results of the in vivo rabbit radius defect repair indicated that rapid mineralization and new bone formation could be observed on the composites with 22 and 33 wt % PBLG. This study revealed that PBLG-g-MHA/PLGA composites might have potential applications in clinical bone repair.

Intracellular calcium ions and morphological changes of cardiac myoblasts response to an intelligent biodegradable conducting copolymer.

A novel biodegradable conducting polymer, PLA-b-AP-b-PLA (PAP) triblock copolymer of poly (l-lactide) (PLA) and aniline pentamer (AP) with electroactivity and biodegradability, was synthesized and its potential application in cardiac tissue engineering was studied. The PAP copolymer presented better biocompatibility compared to PANi and PLA because of promoted cell adhesion and spreading of rat cardiac myoblasts (H9c2 cell line) on PAP/PLA thin film. After pulse electrical stimulation (5 V, 1 Hz, 500 ms) for 6 days, the proliferation ratio, and intracellular calcium concentration of H9c2 cells on PAP/PLA were improved significantly. Meanwhile, cell morphology changed by varying the pulse electrical signals. Especially, the oriented pseudopodia-like structure was observed from H9c2 cells on PAP/PLA after electrical stimulation. It is regarded that the novel conducting copolymer could enhance electronic signals transferring between cells because of its special electrochemical properties, which may result in the differentiation of cardiac myoblasts.

Micro-porous polyetheretherketone implants decorated with BMP-2 via phosphorylated gelatin coating for enhancing cell adhesion and osteogenic differentiation.

Polyetheretherketone (PEEK) is a high-performance semicrystalline thermoplastic polymer that is widely used in the orthopedics treatment. However, due to its biological inertness, the surface modification of PEEK using different methods to improve the biocompatibility remains a significant challenge. Herein, we attempted to use the covalently coating of phosphorylated gelatin loaded with bone morphogenetic protein 2 (BMP-2) on hydroxylated micro-porous PEEK films for enhancing the biological activity. Environmental scanning electron microscope (ESEM), fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and water contact angle measurements were applied to characterize the surface of modified or untreated PEEK films. The influence on cell adhesion, proliferation and differentiation was evaluated by culturing of mouse pre-osteoblasts (MC3T3-E1) on different modified PEEK substrates in vitro. Surface characterization showed that the modification was successfully performed on PEEK films. The biological results indicated that surface modification of micro-porous PEEK using phosphorylated gelatin significantly promoted cell adhesion and proliferation. And the osteogenic differentiation was effectively improved while loading with different amounts of BMP-2. Findings from this study indicated that this novel biological modification on PEEK films might be helpful for altering its biological inertness and further expand its medical applications as a kind of orthopedic implants.

Preparation and Characterization of Silver Sulfadiazine-Loaded Polyvinyl Alcohol Hydrogels as an Antibacterial Wound Dressing.

In this study, we prepared a series of silver sulfadiazine (AgSD)-loaded polyvinyl alcohol (PVA) hydrogels via electron beam (e-beam) irradiation. Our objective was to explore the influence of e-beam irradiation on the chemical structure and crystallinity of AgSD and the antibacterial properties of AgSD/PVA hydrogels. Prior to irradiation, we mixed AgSD in PVA solution in 2 forms, either suspended in water (WS) or dissolved in ammonia solution (AS). We noted that nano silver was released from AgSD/PVA-AS hydrogels immersed in deionized water, while it would not happen in AgSD/PVA-WS hydrogels. Both kinds of AgSD/PVA hydrogels exhibited good antibacterial activities against gram-negative Escherichia coli and gram-positive Staphylococcus aureus. And their antibacterial activity was not obviously affected by different dosages of e-beam irradiation. Moreover, the antibacterial activity of the AgSD/PVA-WS hydrogels was stronger than that of AgSD/PVA-AS. Accordingly, the cell cytotoxicity of the AgSD/PVA-WS hydrogels was higher than that of AgSD/PVA-AS. Our study results reveal that e-beam irradiation of PVA solution with dispersed AgSD is a simple and efficient way to prepare AgSD/PVA hydrogels, which might be an ideal antibacterial wound dressing.

In situ polymerization of poly(γ-benzyl-l-glutamate) on mesoporous hydroxyapatite with high graft amounts for the direct fabrication of biodegradable cell microcarriers and their osteogenic induction.

Large-scale cell culture for cell expansion in tissue engineering is currently a major focus of research. One method to achieve better cell amplification is to utilize microcarriers. In this study, different amounts of poly(γ-benzyl-l-glutamate) (PBLG) (from 11 wt% to 50 wt%) were grafted on mesoporous hydroxyapatite (MHA) by the in situ ring opening polymerization of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA), and biodegradable and biocompatible PBLG-g-MHA microcarriers were directly fabricated using the oil-in-water (O/W) solvent-evaporation technique for bone tissue engineering. The amount of grafted PBLG could be controlled by adjusting the feed ratio of MHA and BLG-NCA. The relationships between sphere morphology and graft amount or solution concentration were explored. Furthermore, cytological assays were performed to evaluate the biological properties of the PBLG-g-MHA microcarriers. For a solution concentration of 3% (w/v) and PBLG graft amounts of 33 wt% and 50 wt%, the microspheres could be harvested with optimal spherical shapes. In vitro cell culture revealed that the PBLG-g-MHA microspheres had favorable properties for cell proliferation and significantly enhanced the osteogenic differentiation of MC3T3-E1 cells and bone matrix formation.

Controlled synthesis of high molecular weight poly(3-hexylthiophene)s via Kumada catalyst transfer polycondensation with Ni(IPr)(acac)2 as the catalyst.

The controlled synthesis of poly(3-hexylthiophene)s (P3HTs) with number-average molecular weights (Mns) up to 350 kg mol(-1) has been realized with Ni(IPr)(acac)2 as the catalyst.

Synthesis and characterization of the titanium complexes bearing two ß-enaminoketonato ligands with electron withdrawing groups/modified phenyls and their behaviors for ethylene (co-)polymerization.

A series of new titanium complexes with two asymmetric bidentate ß-enaminoketonato [N,O] ligands (2b-t), [PhN=C(CF(3))CHC(Ar)O](2)TiCl(2) (2b, Ar = -C(6)H(4)F(o); 2c, Ar = -C(6)H(4)F(m); 2d, Ar = -C(6)H(4)F(p); 2e, Ar = -C(6)H(4)Cl(p); 2f, Ar = -C(6)H(4)OMe(p); 2g, Ar = -C(6)H(4)CF(3)(p); 2h, Ar = -C(6)H(4)CF(3)(m); 2i, Ar = -C(6)H(4)CF(3)(o); 2j, Ar = -C(6)H(4)Cl(o); 2k, Ar = -C(6)H(4)Br(o); 2l, Ar = -C(6)H(4)I(o); 2m, Ar = -C(6)H(3)F(2)(2,4); 2n, Ar = -C(6)H(3)F(2)(2,6); 2o, Ar = -C(6)H(3)F(2)(3,4); 2p, Ar = -C(6)H(3)F(2)(3,5); 2q, Ar = -C(6)F(5); 2r, Ar = C(6)F(4)OMe; 2s, Ar = -C(6)H(3)Cl(2)(2,6); 2t, Ar = -C(6)H(3)Cl(2)(2,5)), have been synthesized based on substituted acetophenones. X-Ray analyses reveal that complexes 2h, 2k, 2m, and 2n adopt distorted octahedral geometry around the titanium center, in which the two chloride ligands are situated in the cis-orientation. 2s also adopts distorted octahedral geometry, but the two chloride ligands in it are situated in the trans-orientation due to the increase of the steric effect of the phenyl derived from the acetophenone. The influence of the substituent effects on catalyst performance, including catalytic activities and the molecular weight distribution of the polymers obtained, was investigated in detail. With modified methylaluminoxane (MMAO) as a cocatalyst, complexes 2b-r and 2t are active catalysts for ethylene polymerization at room temperature, and produce high molecular weight polymers. It is observed that the catalytic activities are significantly enhanced by introducing some electron-withdrawing groups, such as -F, -Cl and -CF(3), into the suitable positions of the phenyl ring close to the oxygen donor. It should be noted that complexes 2c-i, 2p, 2n and 2t are also capable of promoting the living copolymerization of ethylene with norbornene at room temperature, yielding high molecular weight copolymers with narrow molecular weight distributions (PDI = 1.05-1.30).

Synthesis and characterization of the titanium complexes bearing two regioisomeric trifluoromethyl-containing enaminoketonato ligands and their behavior in ethylene polymerization.

A series of new titanium complexes bearing two regioisomeric trifluoromethyl-containing enaminoketonato ligands (3a-h and 6a-h), [PhN=CRCHC(CF3)O]2TiCl2 (3a, R = Me; 3b, R = n-C5H11; 3c, R = i-Pr; 3d, R = Cy; 3e, R = t-Bu; 3f, R = CH=CHPh; 3g, R = Et; 3h, R = n-C11H23) and [PhN=C(CF3)CHC(R)O]2TiCl2 (6a, R = Ph; 6b, R = n-C5H11; 6c, R = i-Pr; 6d, R = Cy; 6e, R = t-Bu; 6f, R = CH=CHPh; 6g, R = CHPh2; 6h, R = CF3) have been synthesized and characterized. X-ray crystal structures analyses suggest that complexes 3c-e and 6c-d all adopt a distorted octahedral geometry around the titanium center. Complexes 3c, 3d and 6c display a cis-configuration of the two chlorine atoms around the titanium center, while complex 6d shows a trans-configuration of the two chlorine atoms. Especially, the configurational isomers (cis and trans) of complex 3e were identified both in solution and in the solid state by NMR and X-ray analyses. With modified methylaluminoxane as a cocatalyst, all the complexes are active towards ethylene polymerization, and produce high molecular weight polymers. With the variation of the relative position of the imino group and the trifluoromethyl group of the beta-enaminoketonato ligands, the polymerization behavior of the catalysts changed remarkably. It is observed that the substituent directly joined to the carbonyl in the ligands plays an important role for both the catalytic activities and the properties of the polymers produced.