Fabrication of chitosan based nanocomposite with legumain sensitive properties using charge driven self-assembly strategy.

Chitosan (CS) based nanoparticles (NPs) have several advantages in delivering drugs. They are usually prepared in a micro-emulsion solvent system but this route can leave significant levels of potentially harmful organic solvent residue in the NPs. In this study, we prepared CS based nanocomposites using charge driven self-assembly in an aqueous buffer, thus avoiding the use of organic solvents. Doxorubicin (DOX) was covalently attached to positive charged CS with a legumain substrate peptide to confer targeted drug release property, since legumain is often overexpressed in tumors or tumor associated micro environments. This DOX prodrug solution interacted with negative charged methoxyl poly (ethylene glycol)-block-poly (glutamic acid) copolymer (PEG-PGA) in an aqueous buffer forming nanocomposite with a regular morphology. The particle size and zeta potential of these NPs was regulated by the addition of different PEG-PGA concentrations into the DOX prodrug solution. Due to its potential for legumain triggered release, this DOX NP exhibited enhanced cytotoxicity against choroidal melanoma cell line (Mum-2C) and reduced cytotoxicity on normal human corneal epithelial cells (HCEC), suggesting a good potential for enhanced targeted delivery of chemotherapeutic agents. A chitosan based nanocomposite with legumain sensitive properties are rapidly controllable prepared in aqueous buffer by charge driven self-assembly strategy, without using micro-emulsion solvent system and cross-linking agents.

Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease.

Introduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED). Methods: The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael's addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction. Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission. Conclusion: NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.

Efficiency Encapsulation of FK506 with New Dual Self-Assembly Multi-Hydrophobic-Core Nanoparticles for Preventing Keratoplasty Rejection.

Nanoparticles self-assembled by amphiphilic copolymers for loading hydrophobic molecules are intensively investigated. However, their hydrophobic molecule-loading capacity is low due to the limitation of hydrophobic groups in these copolymers. In this regard, new lysine oligomer-based multi-hydrophobic side chain polymers (MHCPs) are synthesized by polymerization of γ-benzyl-l glutamate N-carboxy anhydride initiated by side-chain primary amino groups in lysine oligomer. Each hydrophobic side chain in MHCPs can be self-assembled by hydrophobic interaction to form multi-hydrophobic-core nanoparticles (MHC-NPs) with silkworm cocoon-, grape cluster-, and butterfly-like shapes (depending on hydrophobic-side-chains lengths). To increase their stability, MHC-NPs are dually self-assembled with polyethylene glycol-polyglutamic acid through charge interaction. Each hydrophobic core in MHC-NPs serves as a carrier for hydrophobic molecules, endowing their nanostructure with high loading capacity. MHC-NPs are employed to load tacrolimus (also known as FK506), and the loading amount is 18% and the loading efficiency is 80%, which are higher than those of previously reported nanomicelles self-assembled by linear amphiphilic copolymers. Topical administration of FK506-loaded nanoparticle (FK506-NP) can significantly prolong retention of FK506 on the eye surface. FK506-NP exhibits higher in vivo immunosuppressive effects than free FK506 and commercial FK506 eye drop, as well as a better protective effect against immunotoxicity in the corneal grafts after keratoplasty.

Electrospun fibrous scaffold of hydroxyapatite/poly (ε-caprolactone) for bone regeneration.

Development of fibrous scaffold of hydroxyapatite/biopolymer nanocomposite offers great potential in the field of bone regeneration and tissue engineering. Hydroxyapatite (HA)/poly (ε-caprolactone) (PCL) fibrous scaffolds were successfully prepared by electrospinning dopes containing HA and PCL in this work. It was found that pre-treating HA with γ-glycioxypropyltrimethoxysilane (A-187) was effective in improving HA dispersion both in solutions and in a PCL matrix. Mechanical properties of the scaffolds were greatly enhanced by the filling of A187-HA. The bioactivity of PCL was remarkably improved by the addition of HA and A187-HA. Fibroblasts and osteoblasts were seeded on scaffolds to evaluate the effect of A-187 on biocompatibility of HA/PCL composites. Based on this study, good dispersion of HA in PCL matrix was granted by pretreatment of HA with A-187 and A187-HA/PCL fibrous scaffolds were obtained by electrospinning. These results demonstrated that the scaffolds may possess improved mechanical performance and good bioactivity due to A187-HA incorporation.

Construction of Injectable Self-Healing Macroporous Hydrogels via a Template-Free Method for Tissue Engineering and Drug Delivery.

Because of their ease of handling and excellent biocompatibility, injectable macroporous hydrogels have received a considerable interest in the fields of tissue engineering and drug delivery systems because of their unique application in minimally invasive surgical procedures. In this study, in situ forming, injectable, macroporous, self-healing gelatin (GE)/oxidized alginate (OSA)/adipic acid dihydrazide (ADH) hydrogels were prepared using a high-speed shearing treatment and were stabilized by Schiff base reaction and acylhydrazone bonds. Their injectability, self-healing ability, rheology, microstructure, equilibrium water content, and in vitro biodegradation were investigated. We found that the injectable GE/OSA/ADH precursors remained in a liquid form and flowed easily for several minutes at room temperature, but however, gelled rapidly at body temperature. The gelation time could be regulated by varying the ratio of GE, OSA, and ADH. The obtained hydrogels had an interconnected macroporous structure and self-healing ability. The porosity of hydrogels was in the range of approximately 60-83%, and pore size varied from approximately 125-380 µm. The porous structure of hydrogel was visualized by field-emission scanning electron microscope, micro-computed tomography, and laser confocal microscope. Human epidermal growth factor was loaded by in situ mixing in GE/OSA/ADH hydrogels and was released with good bioactivity as evaluated by ELISA. Moreover, L929 cells proliferated on GE/OSA/ADH hydrogels, as verified by Cell Counting Kit-8 and LIVE/DEAD assays. Furthermore, encapsulation of NIH 3T3 cells within GE/OSA/ADH hydrogels demonstrated that the hydrogel can support cell survival, proliferation, and migration. In vivo studies showed that the hydrogels had a good injectability, in situ gelation, and tissue biocompatibility. Therefore, GE/OSA/ADH hydrogel represented a novel and safe injectable macroporous self-healing hydrogel for tissue engineering scaffold and drug delivery vehicle purposes.

Fabrication of nonfouling, bactericidal, and bacteria corpse release multifunctional surface through surface-initiated RAFT polymerization.

Infections after surgery or endophthalmitis are potentially blinding complications caused by bacterial adhesion and subsequent biofilm formation on the intraocular lens. Neither single-function anti-adhesion surface nor contacting killing surface can exhibit ideal antibacterial function. In this work, a novel (2-(dimethylamino)-ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine) (p (DMAEMA-co-MPC)) brush was synthesized by "grafting from" method through reversible-addition fragmentation chain transfer polymerization. 1-Bromoheptane was used to quaternize the p (DMAEMA-co-MPC) brush coating and to endow the surface with bactericidal function. The success of the surface functionalization was confirmed by atomic force microscopy, water contact angle, and spectroscopic ellipsometry. The quaternary ammonium salt units were employed as efficient disinfection that can eliminate bacteria through contact killing, whereas the 2-methacryloyloxyethyl phosphorylcholine units were introduced to suppress unwanted nonspecific adsorption. The functionalized poly(dimethyl siloxane) surfaces showed efficiency in reducing bovine serum albumin adsorption and in inhibiting bacteria adhesion and biofilm formation. The copolymer brushes also demonstrated excellent bactericidal function against gram-positive (Staphylococcus aureus) bacteria measured by bacteria live/dead staining and shake-flask culture methods. The surface biocompatibility was evaluated by morphology and activity measurement with human lens epithelial cells in vitro. The achievement of the p (DMAEMA+-co-MPC) copolymer brush coating with nonfouling, bactericidal, and bacteria corpse release properties can be used to modify intraocular lenses.

Construction of a temperature-responsive terpolymer coating with recyclable bactericidal and self-cleaning antimicrobial properties.

Once a biomedical implant is implanted into a human body, proteins and bacteria can easily colonize the implant, and subsequently, a biofilm can grow on the surface. A biofilm can protect the inhabiting bacteria against macrophages and neutrophil cell attack from the host immune system. The most important issue for artificial antibacterial surfaces is the accumulation of the bacteria corpse after they are killed by contact, which promotes further adhesion of bacteria and biofilm formation. Therefore, we constructed a novel multifunctional bactericidal and fouling release antibacterial surface through the combination of temperature-responsive N-vinylcaprolactam (VCL), hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC) and a bactericidal quaternary ammonium salt (2-(dimethylamino)-ethyl methacrylate (DMAEMA+)). The terpolymer coating was prepared through surface-initiated reversible addition-fragmentation chain-transfer (RAFT) polymerization and characterized using water contact angle measurements, atomic force microscopy and spectroscopic ellipsometry. At a temperature above the lower critical solution temperature (LCST), the P(VCL-co-DMAEMA+-co-MPC) terpolymer coating was in a compressed and hydrophobic state with low moisture content, which displayed bactericidal efficiency against Gram-positive Staphylococcus aureus. The coating could be switched into a relatively hydrophilic surface at a temperature below the LCST, which showed self-cleaning properties against both bacteria and bovine serum albumin. The functionalized surface showed good biocompatibility against human lens epithelial cells as evaluated by morphology studies and activity measurements.

Copolymer Brushes with Temperature-Triggered, Reversibly Switchable Bactericidal and Antifouling Properties for Biomaterial Surfaces.

The adherence of bacteria and the formation of biofilm on implants is a serious problem that often leads to implant failure. A series of antimicrobial coatings have been constructed to resist bacterial adherence or to kill bacteria through contact with or release of antibacterial agents. The accumulation of dead bacteria facilitates further bacterial contamination and biofilm development. Herein, we have designed and constructed a novel, reversibly switchable bactericidal and antifouling surface through surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization to combine thermally responsive N-isopropylacrylamide (NIPAAm) and bactericidal quaternary ammonium salts (2-(dimethylamino)-ethyl methacrylate (DMAEMA+)). Measurements of spectroscopic ellipsometry and water contact angle and X-ray photoelectron spectroscopy were used to examine the process of the surface functionalization. The temperature-responsive P(DMAEMA+-co-NIPAAm) copolymer coating can switch by phase transition between a hydrophobic capturing surface at high temperatures and a relatively hydrophilic antifouling surface at lower temperatures. The quaternary ammonium salts of PDMAEMA+ displayed bactericidal efficiency against both Escherichia coli and Staphylococcus aureus. The functionalized surface could efficiently prevent bovine serum albumin adsorption and had good biocompatibility against human lens epithelial cells.

Application research of plasma-enhanced electrochemical surface ceramic-coating technology on titanium implants.

Plasma electrochemical surface ceramic coating (PECC) is an enhanced electrochemistry technique accomplished by means of plasma arc discharge in an electrolyte medium obtain coating structures on valve-metal surfaces. Oxide films of titanium obtained by PECC in the electrolyte of sodium phosphate were investigated. The film was composed mainly of TiO2 in the form of anatase and rutile and enriched with Na and P elements on their surfaces. Their apatite-inducing ability was also evaluated in a simulated body fluid (SBF). When immersed in SBF for over 30 days, an oriented hydroxy-carbonate-apatite was induced on the surface of the films, which suggests the PECC-treated titanium has the promising positive biological response.

Application of 5-Fluorouracil-Polycaprolactone Sustained-Release Film in Ahmed Glaucoma Valve Implantation Inhibits Postoperative Bleb Scarring in Rabbit Eyes.

This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve implantation, and group C received Ahmed glaucoma valve implantation. Postoperative observations were made of the anterior segment, intraocular pressure, central anterior chamber depth, blebs, drainage tube, and accompanying ciliary body detachment. The pathology of the blebs and surrounding tissues were observed at month 3 postoperatively. We revealed that the 5-Fu-polycaprolactone sustained-release film maintained a release concentration range of 13.7 ± 0.12 to 37.41 ± 0.47 µg/ml over three months in vitro. Postoperatively, diffuse blebs with ridges were found in all eyes in group A, two blebs were observed in group B, and no bleb formation was present in group C. The postoperative central anterior chamber depth in group A was significantly less than that of the other two groups. The postoperative intraocular pressure of group A stabilized at 6.33-8.67 mmHg, whereas that of group C gradually remained at 7.55-10.02 mmHg. The histopathology showed that the fibrous tissue thickness of the blebs in group A was significantly thinner than that of the other groups. We conclude that the 5-Fu-polycaprolactone sustained-release film had a sustained drug release effect, which promoted the inhibition of bleb scarring after Ahmed glaucoma valve implantation.

Porous silicon oxide-PLGA composite microspheres for sustained ocular delivery of daunorubicin.

A water-soluble anthracycline antibiotic drug (daunorubicin, DNR) was loaded into oxidized porous silicon (pSiO2) microparticles and then encapsulated with a layer of polymer (poly lactide-co-glycolide, PLGA) to investigate their synergistic effects in control of DNR release. Similarly fabricated PLGA-DNR microspheres without pSiO2, and pSiO2 microparticles without PLGA were used as control particles. The composite microparticles synthesized by a solid-in-oil-in-water emulsion method have mean diameters of 52.33±16.37µm for PLGA-pSiO2_21/40-DNR and the mean diameter of 49.31±8.87µm for PLGA-pSiO2_6/20-DNR. The mean size, 26.00±8µm, of PLGA-DNR was significantly smaller, compared with the other two (P<0.0001). Optical microscopy revealed that PLGA-pSiO2-DNR microspheres contained multiple pSiO2 particles. In vitro release experiments determined that control PLGA-DNR microspheres completely released DNR within 38days and control pSiO2-DNR microparticles (with no PLGA coating) released DNR within 14days, while the PLGA-pSiO2-DNR microspheres released DNR for 74days. Temporal release profiles of DNR from PLGA-pSiO2 composite particles indicated that both PLGA and pSiO2 contribute to the sustained release of the payload. The PLGA-pSiO2 composite displayed a more constant rate of DNR release than the pSiO2 control formulation, and displayed a significantly slower release of DNR than either the PLGA or pSiO2 formulations. We conclude that this system may be useful in managing unwanted ocular proliferation when formulated with antiproliferation compounds such as DNR.

Sustained release of triamcinolone acetonide from an episcleral plaque of multilayered poly-ε-caprolactone matrix.

A subtenon injection of triamcinolone acetonide (TA) is a widely used treatment modality for various chorio-retinal diseases. Although it is less invasive than intravitreal injection, it can produce dose-associated ocular complications and has the disadvantages associated with systemic TA exposure. In this study we have developed and evaluated an episcleral film consisting of TA and poly-ε-caprolactone (PCL). The films were prepared by spraying a mixture of PCL in dichloromethane and TA in acetone. The films were produced as 6mm wide and 12 mm long episcleral plaques. X-ray diffraction demonstrated an even distribution of TA crystals in PCL, although the TA was less crystalized than a native TA control. Fourier transform infrared spectroscopy revealed effective integration of TA within the PCL matrix. An in vitro study of the release of TA from the episcleral plaques showed that TA release rate was only 40-50% that of the equivalent native TA control. An in vivo study demonstrated that the plaques were well tolerated in rabbit eyes with significantly less systemic TA exposure. The episcleral plaques provided therapeutic vitreous TA levels for 3 months, while TA levels in the vitreous were detectable for only 1 month following an equivalent dose by subtenon TA injection. The PCL-TA 30-60 episcleral plaque may be further developed as a better alternative treatment for many chronic vitreo-retinal diseases, providing longer and controlled release and fewer drug-associated complications than those associated with a conventional subtenon injection of TA.

[Apatite-forming ability of pure titanium implant after micro-arc oxidation treatment].

OBJECTIVE: To investigate the apatite forming ability of pure titanium implant after micro-arc oxidation treatment in simulated body fluid (SBF) and obtain implants with calcium phosphate (Ca-P) layers. METHODS: The implants were immersed in (SBF) after micro-arc oxidation treatment for different time lengths, and their apatite forming ability and the morphology and constituents of the Ca-P layers formed on the sample surface were analyzed using X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, and energy dispersive electron probe. RESULTS: After immersion in SBF, large quantities of Ca-P layers were induced on the surface of the samples. The Ca-P layers were composed of octacalcium phosphate and carbonated hydroxyapatite, and the crystals showed a plate-like morphology with an oriented growth. CONCLUSION: The implants with micro-arc oxidation treatment show good apatite forming ability on the surface with rich calcium and phosphorus elements. The formed layers are composed of bone-like apatite including octacalcium phosphate and carbonated hydroxyapatite.

Cytotoxicity and biocompatibility evaluation of N,O-carboxymethyl chitosan/oxidized alginate hydrogel for drug delivery application.

In this paper, covalently cross-linked hydrogel composed of N,O-carboxymethyl chitosan and oxidized alginate was developed intending for drug delivery application. In vitro/vivo cytocompatibility and biocompatibility of the developed hydrogel were preliminary evaluated. In vitro cytocompatibility test showed that the developed hydrogel exhibited good cytocompatibility against NH3T3 cells after 3-day incubation. According to the results of acute toxicity test, there was no obvious cytotoxicity for major organs during the period of 21-day intraperitoneal administration. Meanwhile, the developed hydrogel did not induce any cutaneous reaction within 72 h of subcutaneous injection followed by slow degradation and adsorption with the time evolution. Moreover, the extraction of developed hydrogel had nearly 0% of hemolysis ratio, which indicated the good hemocompatibility of hydrogel. Based on the above results, it may be concluded that the developed N,O-carboxymethyl chitosan/oxidized alginate hydrogel with non-cytotoxicity and good biocompatibility might suitable for the various drug delivery applications.

Preparation and characterization of chitosan nanopores membranes for the transport of drugs.

In this paper, a novel chitosan nanopores membrane was developed by selective dissolution of its composition. Polyethylene glycol (PEG) as the porogen was selected to generate the nanopores structure of chitosan membrane. As the observation with scanning electron microscopy (SEM), we could find that the PEG content was greatly influenced on the structure of chitosan membrane. As the PEG content was larger than 50%, the chitosan nanopores membrane could successfully developed. Differential scanning calorimeter (DSC) measurement revealed that the PEG component could not be completely dissolved from the membrane and there was presence the possible interaction (hydrogen bond) between two components. Water adsorption test suggested that the obtained membranes have the great capacity of water adsorption ranging from 162.4 ± 22.5% to 321.5 ± 6.5%. In vitro degradation experiment showed that the obtained chitosan membranes have good biodegradability in the lysozyme solution. The permeability test was performed with two model drugs: vitamin B12 (non-ionic water-soluble drug) and sodium sulfamerazine (ionic water-soluble drug). And the results showed that these two drugs have significant differences in the permeability, indicating that chitosan nanopores membranes can potentially be used to the transport of drugs with controlled diffusion manner.

Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles.

The use of single chemotherapeutic drug has shown some limitations in anti-tumor treatment, such as development of drug resistance, high toxicity and limited regime of clinical uses. The combination of two or more therapeutic drugs is feasible means to overcome the limitations. Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. Attempts have been made to deliver chemotherapeutic drugs simultaneously using drug carriers, such as micelles, liposomes, and inorganic nanoparticles (NPs). Here we reported core-shell NPs that were doubly emulsified from an amphiphilic copolymer methoxy poly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA). These NPs offered advantages over other nanocarriers, as they were easy to fabricate by improved double emulsion method, biocompatible, and showed high loading efficacy. More importantly, these NPs could co-deliver hydrophilic doxorubicin (DOX) and hydrophobic paclitaxel (TAX). The drug-loaded NPs possessed a better polydispersity, indicating that they are more readily subject to controlled size distribution. Studies on drug release and cellular uptake of the co-delivery system demonstrated that both drugs were effectively taken up by the cells and released simultaneously. Furthermore, the co-delivery nanocarrier suppressed tumor cells growth more efficiently than the delivery of either DOX or TAX at the same concentrations, indicating a synergistic effect. Moreover, the NPs loading drugs with a DOX/TAX concentration ratio of 2:1 showed the highest anti-tumor activity to three different types of tumor cells. This nanocarrier might have important potential in clinical implications for co-delivery of multiple anti-tumor drugs with different properties.

Ectopic osteogenic ability of calcium phosphate scaffolds cultured with osteoblasts.

Bone substitute materials can induce bone formation when combined with mesenchymal stem cells (MSC). The aim of the current study was to examine in vivo ectopic bone formation with MSC on tricalcium phosphate (TCP) ceramics. Osteoblasts isolated from bone marrow stromal cells (BMSCs) of New Zealand rabbits were cultured with TCP ceramics for 10 days, followed by implantation of the cultured TCP ceramics into the rabbit dorsum muscle. The cultured TCP and in vivo new bone formation with TCP biodegradation were evaluated histologically. Scanning electron microscopy showed that the surface of the cultured TCP ceramics was filled by osteoblasts with a cell-free zone in the central area. New bone was formed on the cultured TCP ceramics with signs of gradual degradation of TCP ceramics at 8 weeks of implantation, indicating that TCP could be a potential scaffold for seeding cells used for development of bioengineering tissues.

Characterization and biocompatibility of nanohybrid scaffold prepared via in situ crystallization of hydroxyapatite in chitosan matrix.

Hydroxyapatite (HAP) precursor solution was first mixed with an acetic acid chitosan (CS) solution. The mixture was then lyophilized to form the original scaffold, which stored the HAP precursors. The nano HAP crystallized homogeneously from the CS matrix during the alkaline treatment to form a nanohybrid scaffold. Scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) were used to investigate the fabrication process of the nanohybrid scaffold. XRD results showed that the in situ deposited mineral (HAP) in the scaffold has phase structure similar to natural bone. FTIR and XPS results indicated that CS's hydroxyl group, amino and amide regulated the nano HAP crystallization process, which resulted in the nano homogeneous distribution of nano HAP and provided nano topographical features for the nanohybrid scaffold. MTT testing and SEM images of human bone mesenchymal stem cells (hBMSCs) cultures revealed the attachment and growth of hBMSCs in the biocomposite scaffold. Cell morphology and viability data showed that the nanohybrid composite scaffold is suitable for use in bioapplications.

Superior biocompatibility and osteogenic efficacy of micro-arc oxidation-treated titanium implants in the canine mandible.

The aim of this paper is to test implantation outcomes and osteogenic efficacy of plasma micro-arc oxidation (MAO)-treated titanium implants in dogs. Thirty-six pure titanium implants (18 MAO-treated, 18 untreated) were inserted into the mandibles of nine adult beagles and allowed to heal under non-weight-bearing conditions. Implant stability and interface characteristics were evaluated at 4, 8 and 12 weeks post-implantation. Methods included scanning electron microscopy, mechanical testing, histological analysis and computer-quantified tissue morphology. Osseointegration was achieved in both groups, but occurred earlier and more extensively in the MAO group. Areas of direct bone/implant contact were approximately nine times higher in the MAO group than in the control group at 12 weeks (65.85% versus 7.37%, respectively; p < 0.01). Bone-implant shear strength in the MAO group (71.4, 147.2 and 266.3 MPa at weeks 4, 8 and 12, respectively) was higher than in the control group (4.3, 7.1, and 11.8 MPa at weeks 4, 8 and 12, respectively), at all assessments (all, p < 0.01). MAO treatment of titanium implants promotes more rapid formation of new bone, and increases bone-implant shear strength compared to untreated titanium implants.

Hydroxyapatite coatings produced on commercially pure titanium by micro-arc oxidation.

A porous hydroxyapatite (HA) coating on commercially pure titanium was prepared by micro-arc oxidation (MAO) in electrolytic solution containing calcium acetate and beta-glycerol phosphate disodium salt pentahydrate (beta-GP). The thickness, phase, composition morphology and biocompatibility of the oxide coating were characterized by x-ray diffraction (XRD), electron probe microanalysis (EPMA), scanning electron microscopy (SEM) with an energy dispersive x-ray spectrometer (EDS) and cell culture. The thickness of the MAO film was about 20 microm, and the coating was porous and uneven without any apparent interface to the titanium substrates. The result of XRD showed that the porous coating was made up of HA film. The favorable osteoblast cell affinity gives HA film good biocompatibility. HA coatings are expected to have significant uses for medical applications such as dental implants and artificial bone joints.