Integrated GelMA and interleukin 8-loaded liposome composite scaffold for endogenous BMSCs recruitment in bone repair.

Bone repair strategies, based on endogenous stem cell recruitment, can effectively avoid immune rejection and the low utilization of exogenous stem cells. Endogenous stem cells can be recruited to the implantation site by loading chemokines onto bone tissue-engineered scaffolds. However, challenges such as unstable chemokine activity and easy inactivation after implantation remain significant. In the present study, composite fiber scaffolds ((IL8@LIP)-GelMA) consisting of Interleukin 8 (IL8) -loaded liposomes and GelMA were constructed by electrospinning and photocrosslinking, and its ability to recruit bone marrow-derived mesenchymal stem cells (BMSCs) and immunomodulatory effect was investigated. Compared to GelMA loaded directly with IL8, scaffolds of (IL8@LIP)-GelMA demonstrated superior protection of IL8 activity, ensuring a slow and continuous release. Both in vivo and in vitro experiments demonstrated that the (IL8@LIP)-GelMA scaffolds effectively recruited BMSCs to the desired sites. Additionally, the (IL8@LIP)-GelMA scaffolds exhibited the capacity to recruit more macrophages to the implantation site. Importantly, they promoted the polarization of macrophages toward the M2 anti-inflammatory phenotype, facilitating the transition from the inflammatory stage to the tissue repair stage. Therefore, (IL8@LIP)-GelMA scaffolds show great potential for cell-free tissue engineering applications and provide insights into the loading mode of growth factors in scaffolds.

Dendritic Oligoethylenimine Decorated Liposome with Augmented Corneal Retention and Permeation for Efficient Topical Delivery of Antiglaucoma Drugs.

The topically administered glaucoma medications usually encounter serious precorneal drug loss and low corneal penetration, leading to a low bioavailability. In addition, due to the complexity of glaucoma etiology, a single medication is often insufficient. In this work, we report a novel dendritic oligoethylenimine decorated liposome for codelivery of two antiglaucoma drugs, latanoprost and timolol. The liposome showed a uniform nanoscopic particle size, positive surface charge, and excellent dual-drug loading capacity. A prolonged precorneal retention is observed by using this liposomal delivery system. This liposomal delivery system presents increased cellular uptake and tight junctions opening capacity, contributing respectively to the transcellular and paracellular permeation, thereby enhancing the trans-corneal transportation. Following topical administration of one eye drop in brown Norway rats, the dual-drug-loaded liposome formulation resulted in a sustained and effective intraocular pressure reduction as long as 5 days, without inducing ocular inflammation, discomfort, and tissue damage.

Fabrication and Protein Conjugation of Aligned Polypyrrole-Poly(L-lactic acid) Fibers Film with the Conductivity and Stability.

The conducting composite scaffold, including fiber-cores of aligned poly(L-lactic acid) (PLLA) and shell-layer of polypyrrole (PPy), was fabricated, and then bovine serum albumin (BSA) was conjugated on the PPy shell-layer. Aligned PLLA fibers (about 300 nm diameter) were obtained by electrospinning and rotating drum collection, and then coated by PPy nanoparticles (NPs, about 50 nm diameter) via chemical oxidation. The surface resistivity of PPy-PLLA fibers film were 0.971, 0.874 kΩ. cm at the fiber's vertical and parallel directions, respectively. The results of PPy-PLLA fibers film immersed in phosphate buffer saline for 8 d indicated that the fibers morphology and the film conductivity were not significantly changed, and the fluorescent images showed that FITC-labeled BSA (FITC-BSA) were successfully conjugated in the fibers film with carbodiimide chemistry, and the largest amount of FITC-BSA conjugated in the fibers film from 100 µg/mL proteins solution was 31.31 µg/cm2 due to lots of poly(glutamic acid) in surface-nanogrooves of the fibers surface. Under electrical stimulation of 100 mV, the fibers film was accompanied the release of all conjugated FITC-BSA with the detachment of some PPy NPs. These results suggested that PPy-PLLA fibers film would be potentially applied in the construction of degradable tissue engineering scaffold with protein factors, especially neurotrophic factors for nerve tissue repair.

Preparation of Polypyrrole-Protein Composite Films and the Electrochemically Controlled Release of Proteins.

It is fabricated that an electrically controlled release system based on the (poly-L-lactic acid)-mixed polypyrrole (PLLA-PPy) films through casting film of PPy and PLLA mixed solution on the glass plate, in which polyglutamic acid (PGlu)-doped PPy nanoparticles (NPs) with -50 nm diameter are synthesized via chemical oxidation. Surface conductivity of the composite film is (3.33 ± 2.01) x 10(-3) S/cm. Bovine serum albumin (BSA), as a model protein drug, is chemically linked onto the composite film via carbodiimide chemistry due to the good surface nano-structure of PLLA-PPy film. The releases of BSA from PLLA-PPy film under constant current and constant voltage can be achieved using the two-electrode electrochemical system. 6 h accumulative releases of BSA are 276 µg/cm2 and 176 µg/cm2 under 3 mA and 1 V electrical stimulation, respectively, accompanied with de-doping of PGlu and separation of a part of PPy NPs from the composite film. The results of cell experiment indicate that PGlu-doped PPy NPs in the prepared composite film have good cyto-compatibility. These results suggest that PPy-PLLA composite film would be able to be applied in the construction of degradable protein-drug-loaded scaffold for nerve tissue repair.

Tumor-targeted paclitaxel-loaded folate conjugated poly(ethylene glycol)-poly(L-lactide) microparticles produced by supercritical fluid technology.

The new biodegradable diblock copolymers poly(ethylene glycol)-poly(L-lactide) (PEG-PLLA) were synthesized and were chemically conjugated with folate (FA) in the PEG terminal ends to form FA-PEG-PLLA. Then the hydrophobic drug paclitaxel (PTX) loaded microparticles (PTX/FA-PEG-PLLA) were produced via solution enhanced dispersion by supercritical fluids (SEDS). These microparticles exhibited sphere-like shape by scanning electron microscopy observation and showed narrow hydrodynamic size distributions by dynamic light scattering measurement. Drug loading of PTX loaded microparticles was about 7-9% and the encapsulation efficiency of PTX loaded microparticles was about 18-23%. Flow cytometry and confocal laser scanning microscope analyses revealed that fluorescein isothiocyanate labeled FA conjugated microparticles presented significantly higher cellular uptake than FA-free group due to the FA-receptor-mediated endocytosis. In vitro cytotoxicity evaluation indicated that FA-PEG-PLLA expressed negligible cytotoxicity to mouse fibroblasts L929 cells. Moreover, PTX/FA-PEG-PLLA microparticles exhibited much higher anti-cancer efficacy than PTX/PEG-PLLA microparticles against human ovarian cancer SKOV3 cells. Nude mice xenografted with SKOV3 cells were used in biodistribution studies, the results indicated that an increased amount of PTX was accumulated in the tumor tissue deal with PTX/FA-PEG-PLLA microparticles. These results collectively suggested that PTX/FA-PEG-PLLA microparticles prepared by SEDS would have potential in anti-tumor applications as a tumor-targeted drug delivery formulation.

Osteoinductive biomaterials: Machine learning for prediction and interpretation.

Biomaterials with osteoinductivity are widely used for bone defect repair due to their unique structures and functions. Machine learning (ML) is pivotal in analyzing osteoinductivity and accelerating new material design. However, challenges include creating a comprehensive database of osteoinductive materials and dealing with low-quality, disparate data. As a standard for evaluating the osteoinductivity of biomaterials, ectopic ossification has been used. This paper compiles research findings from the past thirty years, resulting in a robust database validated by experts. To tackle issues of limited data samples, missing data, and high-dimensional sparsity, a data enhancement strategy is developed. This approach achieved an area under the curve (AUC) of 0.921, a precision of 0.839, and a recall of 0.833. Model interpretation identified key factors such as porosity, bone morphogenetic protein-2 (BMP-2), and hydroxyapatite (HA) proportion as crucial determinants of outcomes. Optimizing pore structure and material composition through partial dependence plot (PDP) analysis led to a new bone area ratio of 14.7 ± 7 % in animal experiments, surpassing the database average of 10.97 %. This highlights the significant potential of ML in the development and design of osteoinductive materials. STATEMENT OF SIGNIFICANCE: This study leverages machine learning to analyze osteoinductive biomaterials, addressing challenges in database creation and data quality. Our data enhancement strategy significantly improved model performance. By optimizing pore structure and material composition, we increased new bone formation rates, showcasing the vast potential of machine learning in biomaterial design.

Preparation, characterization and in vitro release properties of morphine-loaded PLLA-PEG-PLLA microparticles via solution enhanced dispersion by supercritical fluids.

Morphine-loaded poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) (PLLA-PEG-PLLA) microparticles were prepared using solution enhanced dispersion by supercritical CO2 (SEDS). The effects of process variables on the morphology, particles size, drug loading (DL), encapsulation efficiency and release properties of the microparticles were investigated. All particles showed spherical or ellipsoidal shape with the mean diameter of 2.04-5.73 µm. The highest DL of 17.92 % was obtained when the dosage ratio of morphine to PLLA-PEG-PLLA reached 1:5, and the encapsulation efficiency can be as high as 87.31 % under appropriate conditions. Morphine-loaded PLLA-PEG-PLLA microparticles displayed short-term release with burst release followed by sustained release within days or long-term release lasted for weeks. The degradation test of the particles showed that the degradation rate of PLLA-PEG-PLLA microparticles was faster than that of PLLA microparticles. The results collectively suggest that PLLA-PEG-PLLA can be a promising candidate polymer for the controlled release system.

Preparation and In Vitro Evaluation of Thermosensitive Liposomes Targeting Ovarian Cancer.

INTRODUCTION: Liposomes have been widely used in drug delivery systems because the encapsulation of liposomes changes the biological distribution profile and improves the therapeutic indices of various drugs. Thermosensitive liposomes have been proven to be a precise and effective method for cancer therapy in many preclinical studies. However, the lack of specific targeting ability to cancer cells limited their application in safe and efficient chemotherapy. METHODS: In the present study, an ovarian targeting ligand namely WSGFPGVWGASVK (WSG) screened by phage display in vivo was grafted on the thermosensitive phospholipids to prepare the liposomes targeting ovarian cancer cells. WSG was first grafted onto the hydrophilic terminal of DSPEPEG2000 molecules, and then the WSG modified thermosensitive liposomes (WSG-Lipo) were prepared by thin-film hydration method. Doxorubicin hydrochloride (DOX) was used as a model drug to investigate the drug release behavior of liposomes at different temperatures. The specificity of liposomes to SKOV-3 cells was studied by cell uptake in vitro. RESULTS: The WSG-Lipo-DOX could release more DOX at 42°C than at 37°C, showing stronger specificity to SKOV-3 cells and thus selectively inhibiting SKOV-3 cells activity in vitro. CONCLUSION: The active targeting liposome showed potential in improving the specificity of thermosensitive liposomes and would be applied in the chemotherapy combined with a thermotherapy.

Combined photothermal-photodynamic therapy by indocyanine green loaded polydopamine nanoparticles enhances anti-mammary gland tumor efficacy.

Various nano-targeted drug delivery systems have been developed for combined photothermal-photodynamic (PTT-PDT) treatment of tumors due to better outcomes compared with monomodality therapy. Here, we constructed a facile two-step method without core templates to obtain indocyanine green (ICG) loaded-hyaluronic acid (HA) surface-coated polydopamine nanoparticles (IIPH). The prepared nanoparticles demonstrated an excellent photothermal conversion capacity and efficient singlet oxygen production. Both in vitro and in vivo studies proved that IIPH could significantly inhibit the growth of tumor by PTT-PDT combinational treatment. All the results indicated that IIPH NPs hold great potential to be utilized as a new photothermal-photodynamic composite for cancer treatment.

Cu-Chelated polydopamine nanoparticles as a photothermal medium and "immunogenic cell death" inducer for combined tumor therapy.

Chemodynamic therapy (CDT) and photothermal therapy (PTT) have been powerful technologies for tumor ablation. However, how to realize efficient CDT and PTT synergetic tumor ablation through a safe and intelligent system, remains a topic of great research value. Herein, a novel Cu-chelated polydopamine nano-system (Cu-PDA) with surface PEGylation and folate (FA) targeting modification (Cu-PDA-FA) was presented as a photothermal agent (PTA), Fenton-like reaction initiator and "immunogenic cell death" inducer to mediate PTT/CDT synergistical tumor therapy and antitumor immune activation. Primarily, the prepared Cu-PDA NPs possessed elevated photothermal conversion efficiency (46.84%) under the near-infrared (NIR) irradiation, bringing about hyperthermic death of tumor cells. Secondly, Cu-PDA catalyzed the generation of toxic hydroxyl radicals (˙OH) in response to the specific tumor microenvironment (TME) with the depletion of GSH, killing tumor cells with high specificity. Interestingly, the increase in local tumor temperature caused by PTT availed the production of ˙OH, and then the produced toxic ˙OH further led the tumor cells to be more sensitive to heat via impeding the expression of heat shock protein, so the synergistically enhanced PTT/CDT in tumor therapy could be achieved. Most importantly, the synergistical PTT/CDT could cause tumor cell death in an immunogenic way to generate in situ tumor vaccine-like functions, which were able to trigger a systemic antitumor immune response, preventing recurrence and metastasis without any other adjuvant supplementation. Overall, these Cu-PDA NPs will provide inspiration for the construction of a versatile nanoplatform for tumor therapy.

Fe(III)-Chelated Polydopamine Nanoparticles for Synergistic Tumor Therapies of Enhanced Photothermal Ablation and Antitumor Immune Activation.

Both the low energy density of near-infrared (NIR) photothermal conversion during treatment and the recurrence and metastasis after local treatment have been the main obstacles and conundrums in polydopamine-mediated tumor photothermal therapy (PTT). Herein, On the basis of the enhancement of NIR absorption by ligand to metal charge transfer (LMCT) in transition-metal complexes and the activation of antitumor immunity by an appropriate concentration of Fe(III) ions, Fe(III)-chelated PDA nanoparticles (Fe-PDA NPs) with high loading and responsive release of iron ions were synthesized through a prechelation-polymerization method. First, Fe(III) chelated with the catechol groups in DA to form a mono-dopa-Fe(III) chelate, and then the polymerization of dopamine was initiated under alkaline conditions. The results revealed that the mono-dopa-Fe(III) chelate was still the main form of the Fe ion existing in Fe-PDA and was able to greatly enhance the light absorption behaviors of PDA in NIR, resulting a superior photothermal conversion ability (η = 55.5%). Moreover, the existence of Fe(III) also gave Fe-PDA a T1-weighted MRI contrast-enhancement performance (r1 = 7.668 mM-1 s-1) and it would enable the accurate ablation of primary tumors in vivo with Fe-PDA under NIR irradiation by means of the guidance of MRI and thermal imaging. Furthermore, Fe-PDA exhibited better H2O2-responsive biodegradability in comparison to PDA and easily released Fe ions in tumors, which could effectively promote the tumor-associated macrophage (TAM) repolarization to the M1 mode. TAM repolarization combined with the immunogenic cell death (ICD) induced by PTT could effectively enhance the efficacy of immunotherapy, preventing tumor recurrence and metastasis. The design of Fe-PDA nanoparticles should provide more inspiration for structural and functional improvements of melanin-based materials in tumor suppression.

Gene delivery of chitosan-graft-polyethyleneimine vectors loaded on scaffolds for nerve regeneration.

As an important transcription factor, c-Jun could upregulate growth factors expression in Schwann cells (SCs). Arginine-Glycine-Aspartate (RGD)-functionalized chitosan-graft-polyethyleneimine (RCP) gene vectors were prepared through the maleic anhydride & the carbodiimide methods, and electrostatically bound with c-Jun plasmids (pJUN), finally loaded on poly-L-lactic acid/silk fibroin parallel fiber films to fabricate nerve scaffold (RCP/pJUN-PSPF@PGA), which could locally deliver c-Jun plasmids into SCs via the mediation of RGD peptides, and upregulate the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in SCs. After the scaffold was bridged in sciatic nerve defect, the delivery of c-Jun plasmids from RCP/pJUN-PSPF@PGA facilitated SCs to sustain the expressions of NGF, BDNF and vascular endothelial growth factor in the injury field, promoting myelination, axonal growth and microvascular generation and nerve regeneration, muscle reinnervation and functional recovery. These results suggested that RCP/pDNA-PSPF@PGA, as an effective gene delivery platform, could provide a local gene therapy to improve nerve regeneration.

Electrophoretic deposition of porous CaO-MgO-SiO2 glass-ceramic coatings with B2O3 as additive on Ti-6Al-4V alloy.

The sub-micron glass-ceramic powders in CaO-MgO-SiO(2) system with 10 wt% B(2)O(3) additive were synthesized by sol-gel process. Then bioactive porous CaO-MgO-SiO(2) glass-ceramic coatings on Ti-6Al-4V alloy substrates were fabricated using electrophoretic deposition (EPD) technique. After being calcined at 850°C, the above coatings with thickness of 10-150 µm were uniform and crack-free, possessing porous structure with sub-micron and micron size connected pores. Ethanol was employed as the most suitable solvent to prepare the suspension for EPD. The coating porous appearance and porosity distribution could be controlled by adjusting the suspension concentration, applied voltage and deposition time. The heat-treated coatings possessed high crystalline and was mainly composed of diopside, akermanite, merwinite, calcium silicate and calcium borate silicate. Bonelike apatite was formed on the coatings after 7 days of soaking in simulated body fluid (SBF). The bonding strength of the coatings was needed to be further improved.

Ion release behavior of vanadium-doped mesoporous bioactive glass particles and the effect of the released ions on osteogenic differentiation of BMSCs via the FAK/MAPK signaling pathway.

Vanadium is an important trace element in bone and is involved in bone metabolism, bone formation, and bone growth, but the roles of various vanadium ions, especially of pentavalent vanadium, in bone tissue regenerative repair have been underestimated and even misinterpreted for a long time. The main purposes of this study are to investigate the release profile of Si, Ca, P, and V ions from vanadium doped mesoporous bioactive glass (V-MBG) particles and to explore the effect of pentavalent vanadium ions on proliferation and osteogenic differentiation of BMSCs as well as the corresponding osteogenic signaling pathway. On the basis of preparations of V-MBG particles with different pentavalent vanadium contents, the ion release behavior from V-MBG in distilled water and simulated body fluid was systemically investigated. Furthermore, the cytocompatibility and osteogenic effect of V-MBG extracts were studied in rBMSCs, and the related molecular mechanisms were preliminarily discussed. The results of dissolution experiments showed that the V ionic concentration exhibited a burst increase and then a sustained slow increase in the two media. The resultant V ions from 1.0V-MBG, 4.0V-MBG and 10.0V-MBG at 21 days were about 1.1, 5.8, and 12.5 mg L-1 in water, respectively, and 1.6, 4.8 and 12.8 mg L-1 in SBF, respectively. The release behaviors of Si, Ca, P, and V ions were evidently affected by high contents of incorporated vanadium. The cellular results indicated that compared to the control and MBG groups, the V(V) ions in V-MBG extracts at about 19.4 µM markedly promoted the proliferation, the gene and protein expression of BMP-2 and COL-I, and the ALP activity of rBMSCs in non-osteoinductive media, but insignificantly stimulated the OCN protein synthesis. More deeply, V(V) ions at about 19.4 µM significantly upregulated the gene and protein expressions of Itga 2b, FAK, and pERK1/2, demonstrating that V(V) ions could regulate osteogenic differentiation of rBMSCs through the activation of the Itga 2b-FAK-MAPK (pERK1/2) signaling pathway. The in vivo results further confirmed that V-MBG induced and promoted new bone formation in the defect area compared to the PGC and PGC/V-M0 groups. These results would contribute to modify the perception about the biocompatibility and osteogenic promotion of pentavalent vanadium at an appropriate concentration.

Photothermal photodynamic therapy and enhanced radiotherapy of targeting copolymer-coated liquid metal nanoparticles on liver cancer.

The maximized therapeutic efficacy in tumor treatment can be achieved with combination therapy. Herein, a metronidazole (MN) and RGD peptides were linked with the copolymer chains of polyacrylic acid (PAA) and polyethylene glycol (PEG) by condensation and Michael addition reactions, respectively, named as RGD-PEG-PAA-MN. Subsequently, liquid-metal (LM) nanoparticles broken by ultrasonication were coated with modified copolymer, forming RGD-PEG-PAA-MN@LM nanoparticles. These nanoparticles with the degradation under an acidic condition could target to tumor cells, and LM of these composited nanoparticles could not only efficiently convert the photoenergy of near infrared (NIR) into thermal energy, but also produce more reactive oxygen species under NIR or X ray irradiation. Furthermore, MN in the composited nanoparticles could enhance their radiation sensitivity of tumor tissues with hypoxia condition. The synergic effect of these nanoparticles on cancer limitation after the sequential radiations of NIR and X ray was significantly higher than the single radiation. In the experiments of tumor bearing mice, the volume of the tumor in RGD-PEG-PAA-MN@LM group at 14th day after two radiations of NIR and X-ray were significantly smaller than LM group, and the tumor of RGD-PEG-PAA-MN@LM group at 14th day after two radiations almost disappeared, suggesting better synergistic effect of RGD-PEG-PAA-MN@LM nanoparticles on photothermal conversion, photodynamics under two irradiations and their enhanced sensitization of X-ray radiation. Our results indicated that the prepared nanoparticles would be applied in the combinational therapy of liver tumor by the photothermal, photodynamic and sensitized radiation.

Preparation of polyethylene glycol-polyacrylic acid block copolymer micelles with pH/hypoxic dual-responsive for tumor chemoradiotherapy.

Block copolymers of poly(ethylene glycol)-poly(acrylic acid) linked with metronidazole (MN-PAA-PEG) were prepared via carbodiimide and esterification methods, and self-assembled into core-shell micelles as nano radiosensitizers and carriers of doxorubicin (DOX) delivery. These DOX/MN-PAA-PEG micelles exhibited good pH value and hypoxia dual-responsive properties via analyzing the change of micelle size and drug‒release behavior under hypoxia humor condition. The results of the cell test indicated that DOX was efficiently delivered by DOX/MN-PAA-PEG micelles into the cell nuclei. Compared to 22.4 % of their DOX release under pH 7.4, the rate of DOX release from DOX/MN-PAA-PEG micelles under reducing condition (pH 5.0) was up to 55.9 %. DOX-loaded micelles under 600 MU electron radiation and hypoxia induced the rapidest apoptosis of the tumor-cells, indicating the synergistic effect of their radiotherapy and chemotherapy from the prepared micelles. In vivo investigation and fluorescence imaging revealed that MN-PAA-PEG possessed no toxicity on main organs, and DOX/MN-PAA-PEG micelles were mainly accumulated in the tumor site at 10 h of post-injection, suggesting their good passive tumor-targeted effect. These results suggested that DOX/MN-PAA-PEG micelles were promising candidates for chemoradiotherapy on tumor.

Polydopamine/carboxylic graphene oxide-composited polypyrrole films for promoting adhesion and alignment of Schwann cells.

Polydopamine (PDA)- and carboxylic graphene oxide (CGO)-composited polypyrrole (PPy) films were prepared via electrospinning of poly-l-lactic acid (PLLA), electrodeposition of PPy blended with CGO and polymerization of dopamine (PDA/CGO/PPy-PLLA), and its surface conductivity and elastic modulus reached to ∼17.3 S/cm and ∼260 MPa, respectively. PDA composition could maintain the higher conduction and elastic modulus of this film after the immersion of 3 w, due to the stronger force between PDA molecule and CGO sheets or PPy particles. The results of cell experiments indicated the better adhesion and higher expression of neural proteins in rat Schwann cells (RSCs) on PDA/CGO/PPy-PLLA films, because the composition of PDA provided more absorption and immobilization site for proteins and the regular coating of PDA particles on the CGO sheets reduced the potential damage of Graphene derivatives on the cell membrane integrity. Electrical stimulation (ES) could facilitate ∼31 % of RSCs to align along the current direction on PDA/CGO/PPy-PLLA films, significantly higher than those on PPy-PLLA and CGO/PPy-PLLA films. A mechanism about the cell alignment on films with ES was proposed: the movement of the cytomembrane proteins under ES and their linkage with serum proteins immobilized by PDA facilitated the extension of growth cone along the ES direction.

[Controlled release of paclitaxel from microparticles containing PLLA and its anti-tumor activity on human ovarian carcinoma cell line].

OBJECTIVE: To prove the PLLA-PTX' efficacy on growth, apoptosis of ovarian cancer cell line SKOV3, and to study the controlled release roles of PLLA for PTX. METHODS: Cultured cells of human ovarian Carcinoma cell Line SKOV3 were treated with PLLA-PTX microparticles and PTX only separately, untreated cells as the control. The proliferation of SKOV3 cells were determined by MTT assay with the morphologic change observed under inverted phase contrast microscope, the apoptosis of cell were demonstrated by FCM and in situ TUNEL technique. RESULTS: The anti-tumor activity of PLLA-PTX microparticles was stronger than PTX alone. A time-dependent and dose-dependent growth inhibition was abserved. At 0.05 micromol/L drug concentration, SKOV3 cell viability experiment demonstrated that the drug formulated in the microparticles was more effective than that formulated in PTX. PLLA-PTX microparticles can increase G2/M period percentage, interrupt the cell cycle proceeding, and inhibit the tumor cells'growth through cell apoptosis. Positive staining for the presence of apoptosis were obtained in SKOV3 cells with PLLA-PTX microparticles. CONCLUSIONS: PLLA-PTX microparticles have strong anti-tumor activity and obviously controlled released effectiveness. It shows longer and stronger controlled anti-tumor activity than paclitaxel alone.

Fabrication of Chitosan/Polypyrrole-coated poly(L-lactic acid)/Polycaprolactone aligned fibre films for enhancement of neural cell compatibility and neurite growth.

OBJECTIVE: Chitosan (CS) and polycaprolactone (PCL) were added into a nerve scaffold of poly(L-lactide acid) (PLLA)/polypyrrole (PPy)-based fibre films to solve the unmatch with the nerve strength and the aseptic inflammation from PLLA. METHODS: Poly (L-lactide acid)-polycaprolactone (PLLA/PCL) fibre films coated with chitosan (CS) and polypyrrole (PPy) were prepared by electrospinning of aligned PLLA/PCL fibres, electrochemical deposition of PPy nanoparticles and in situ doping of CS in PPy. PC12 cells were electrically stimulated with 100 mV for 2 hours every day via CS/PPy-PLLA/PCL fibre film to promote the neurite growth. RESULTS: The surface conductivity and tensile strength of CS/PPy-PLLA/PCL fibre films were 1.03 s/m and 13 MPa, respectively. CS content in fibre films was about 7.5 mg/cm2 , improving the pH value (reached to 5.1) of immersion solution of the fibre film at 16 days. Compared with PPy-PLLA/PCL fibre film, more and longer axons were grown out from PC12 cells cultured on CS/PPy-PLLA/PCL fibre film, indicating the positive effect of CS in fibre film on axon growth. The cell differentiation rate and neurite length on CS/PPy-PLLA/PCL fibre film reached to 38% and 75 µm, respectively. These results suggest the promotion of electrical stimulation on neurite growth and alignment. CONCLUSIONS: A synergistic mechanism about the promotion of CS, electrical stimulation and aligned fibres on PC12 cells differentiation, axon outgrowth was proposed. These results indicated the potential application of CS/PPy-PLLA/PCL fibre film in the field of the nerve repair and regeneration.

A novel customized ceramic bracket for esthetic orthodontics: in vitro study.

BACKGROUND: This study aims to develop a novel process to establish a standardized manufacturing technique of customized esthetic ceramic bracket system (CCB) which could be endowed with individual color and shape to satisfy patients' individual demands. Material characteristics and mechanical parameters of CCB were evaluated. SUBJECTS AND METHODS: CCB virtual models were designed individually according to patient's teeth morphology and clinical demands. 3D printing technology, lost-wax technology, and selected glass-ceramic ingots were employed to fabricate CCB. Scanning electron microscopy (SEM) analyses were performed to characterize the surface morphology of CCB and commercially available brackets (Clarity Advanced; Crystalline VII; Inspire ICE; Damon Q). Static and kinetic frictional resistance (FR), shear bond strength (SBS) and adhesive remnant index (ARI) scores were recorded. One-way analyses of variance (ANOVA) and post-hoc Tukey's HSD multiple tests were used for statistical analyses. RESULTS: Multi-color and multi-transparency raw materials facilitated CCB with a wide range of color options and controllable optical properties to satisfy different esthetic demands of individual orthodontic patients. CCB presented same level of FR as commercially available ceramic brackets did. No significant differences (P ≥ 0.05) of SBS were observed among CCB-ES (treated silane), Clarity Advanced and Crystalline VII groups, and CCB-E (no silane) attained the highest ARI mean score 3. In the preliminary clinical trial, CCB presented excellent color-matching and shape-matching appearances similar to natural teeth, which made it highly invisible from social intercourse distance. CONCLUSIONS: CCB were demonstrated to be an applicable labial orthodontic bracket system with optimized esthetics and biomechanics. We envision that it would be an ideal alternative for patients who pursue esthetic orthodontic treatment but were not likely to take lingual appliances or clear aligners.