Jidong Li

The release properties of silver ions from Ag-nHA/TiO2/PA66 antimicrobial composite scaffolds.

Implant-associated bacterial infection can jeopardize the clinical success of implants and result in loss of supporting bone. The purpose of this study was to develop a novel porous scaffold with long-term antibacterial activity for bone repair or regeneration. Porous nano-hydroxyapatite/titania/polyamide66 scaffolds containing different amounts of silver ions (Ag-nHA/TiO(2)/PA66) were prepared by a phase inversion technique. The release of silver ions from the porous scaffolds in simulated body fluid (SBF) and in the F12 cell culture medium was evaluated via atomic absorption spectrometry. The results showed that the release of Ag(+) was time and concentration dependent, increasing with the immersion time and the silver content in the scaffolds. On the other hand, the release property of Ag(+) was also influenced by the immersion medium. The cumulative Ag(+) release in the F12 medium with time increase parabolically, different from the linear increase or the zero-order release kinetics in the SBF medium. Compared to the slight fluctuation of the Ag(+) release rate in SBF during the whole immersion period, the initial fast release rate and the later sustained release rate of Ag(+) in the F12 medium could be more helpful for preventing implant-associated infection. Since the Ag-nHA/TiO(2) particles were embedded in the PA66 matrix, the long-term-sustained release should be related both to the relaxation of PA macromolecular chains due to the penetration of water and to the slow release of the substituted Ag(+) ions in the HA lattice. The sustained Ag(+) release with time indicates that the composite scaffold is suitable for a long-term antimicrobial application during the scaffold-assisted bone repair or regeneration.

Antibacterial Chitosan Coating on Nano-hydroxyapatite/Polyamide66 Porous Bone Scaffold for Drug Delivery

This study describes a new drug-loaded coating scaffold applied in infection therapy during bone regeneration. Chitosan (CS) containing antibacterial berberine was coated on a nano-hydroxyapatite/polyamide66 (n-HA/PA66) scaffold to realize bone regeneration together with antimicrobial properties. The porous scaffold was fabricated using the phase-inversion method with a porosity of about 84% and macropore size of 400–600 μm. The morphology, mechanical properties and drug-release behavior were investigated at different ratios of chitosan to berberine. The results show that the elastic modulus and compressive strength of the coated scaffolds were improved to 35.4 MPa and 1.7 MPa, respectively, about 7 times and 3 times higher than the uncoated scaffolds. After a burst release of berberine within the first 3 h in PBS solution, a continuous berberine release can last 150 h, which is highly dependent on the coating concentration and suitable for antibacterial requirement of orthopaedic surgery. The bactericidal test confirms a strong antibiotic effect of the delivery system and the minimum inhibitory concentration of the drug is 0.02 mg/ml. Moreover, in vitro biological evaluation demonstrates that the coating scaffolds act as a good matrix for MG63 adhesion, crawl, growth and proliferation, suggesting that the antibacterial delivery system has no cytotoxicity. We expect the drug-delivery system to have a potential application in bone regeneration or defect repair.

Hierarchical structure and mechanical improvement of an n-HA/GCO-PU composite scaffold for bone regeneration

To improve the mechanical properties of bone tissue and achieve the desired bone tissue regeneration for orthopedic surgery, newly designed hydroxyapatite/polyurethane (HA/PU) porous scaffolds were developed via in situ polymerization. The results showed that the molecular modification of PU soft segments by glyceride of castor oil (GCO) can increase the scaffold compressive strength by 48% and the elastic modulus by 96%. When nano-HA (n-HA) particles were incorporated into the GCO-PU matrix, the compressive strength and elastic modulus further increased by 49 and 74%, from 2.91 to 4.34 MPa and from 95 to 165.36 MPa, respectively. The n-HA particles with fine dispersity not only improved the interface bonding with the GCO-PU matrix but also provided effective bioactivity for bonding with bone tissue. The hierarchical structure and mechanical quality of the n-HA/GCO-PU composite scaffold were determined to be appropriate for the growth of cells and the regeneration of bony tissues, demonstrating promising prospects for bone repair and regeneration.

Biological properties of an anti-bacterial membrane for guided bone regeneration: an experimental study in rats

OBJECTIVE The biosafety and efficacy of silver-hydroxyapatite-titania/polyamide nanocomposite (nAg-HA-TiO(2)/PA) membrane as a guided bone regeneration (GBR) barrier were investigated based on a rat subcutaneous and critical-size calvarial defect model. MATERIAL AND METHODS Thirty-six Sprague-Dawley albino rats were divided into nAg-HA-TiO(2)/PA membrane test, expanded polytetrafluoroethylene (e-PTFE) membrane control and blank control. Inflammatory response and bone regeneration in each group were evaluated using morphological, serological, radiographic and histological techniques at 1, 4 and 8 weeks, respectively, after implantation. RESULTS For subcutaneous implantation, slight degradation of nAg-HA-TiO(2)/PA membranes was observed by scanning electron microscope at 4 and 8 weeks. Histopathologic examination demonstrated a thinner layer of granulation tissue in the vicinity of nAg-HA-TiO(2)/PA membranes than that of e-PTFE membranes. For cranial defect implantation, the serum alkaline phosphatase level was remarkably higher in nAg-HA-TiO(2)/PA group than that in e-PTFE group. Radiographic and histomorphometric analysis showed a fully closed cranial defect for both nAg-HA-TiO(2)/PA and e-PTFE groups at 8 weeks. No remarkable difference was found between the two groups regarding the integral optical density of neo-bone at each time interval. CONCLUSION nAg-HA-TiO(2)/PA membranes demonstrated better biocompatibility and similar osteoinductive activity compared with e-PTFE membranes. nAg-HA-TiO(2)/PA composite membranes provided a good prospect for further research and development in anti-bacterial GBR membrane.

Antibiotic delivery system using nano-hydroxyapatite/chitosan bone cement consisting of berberine.

Different concentrations of berberine were mixed with nano-hydroxyapatite/chitosan (n-HA/CS) bone cement to generate an antibiotic drug delivery system for treatment of bone defects. Properties of the system such as setting time, compressive strength, surface morphology, phase compositions, drug release profiles and antimicrobial activity were also characterized. It was shown that the setting time of the cement ranged from 17.03 +/- 0.50 min to 28.47 +/- 0.96 min and the compressive strength changed from 184.00 +/- 7.94 MPa to 120.33 +/- 9.02 MPa with the increase of berberine. The XRD, IR, and SEM analyses suggested that berberine powders were stable in the bone cement in simulated body fluid (SBF). In vitro release of berberine from the bioactive bone cement pellets in SBF could last more than 4 weeks. The release profiles of 1.0 wt % berberine loaded bone cement followed the Higuchi equation at the infusion stage. The drug loaded pellets can inhibit bacterial growth (Staphylococcus aureus) at the standardized berberine minimum inhibitory concentration of 0.02 mg/mL during berberine release from 1 to 28 days. The n-HA/CS bone cement only with 1.0 wt % berberine proved to be an efficient antibiotic drug delivery system.

Property-based design: optimization and characterization of polyvinyl alcohol (PVA) hydrogel and PVA-matrix composite for artificial cornea.

Each approach for artificial cornea design is toward the same goal: to develop a material that best mimics the important properties of natural cornea. Accordingly, the selection and optimization of corneal substitute should be based on their physicochemical properties. In this study, three types of polyvinyl alcohol (PVA) hydrogels with different polymerization degree (PVA1799, PVA2499 and PVA2699) were prepared by freeze-thawing techniques. After characterization in terms of transparency, water content, water contact angle, mechanical property, root-mean-square roughness and protein adsorption behavior, the optimized PVA2499 hydrogel with similar properties of natural cornea was selected as a matrix material for artificial cornea. Based on this, a biomimetic artificial cornea was fabricated with core-and-skirt structure: a transparent PVA hydrogel core, surrounding by a ringed PVA-matrix composite skirt that composed of graphite, Fe-doped nano hydroxyapatite (n-Fe-HA) and PVA hydrogel. Different ratio of graphite/n-Fe-HA can tune the skirt color from dark brown to light brown, which well simulates the iris color of Oriental eyes. Moreover, morphologic and mechanical examination showed that an integrated core-and-skirt artificial cornea was formed from an interpenetrating polymer network, no phase separation appeared on the interface between the core and the skirt.

Preliminary biocompatible evaluation of nano-hydroxyapatite/polyamide 66 composite porous membrane.

Nano-hydroxyapatite/polyamide 66 (nHA/PA66) composite with good bioactivity and osteoconductivity was employed to develop a novel porous membrane with asymmetric structure for guided bone regeneration (GBR). In order to test material cytotoxicity and to investigate surface-dependent responses of bone-forming cells, the morphology, proliferation, and cell cycle of bone marrow stromal cells (BMSCs) of rats cultured on the prepared membrane were determined. The polygonal and fusiform shape of BMSCs was observed by scanning electronic microscopy (SEM). The proliferation of BMSCs cultured on nHA/PA66 membrane tested by the MTT method (MTT: [3-{4,5-dimethylthiazol-2yl}-2,5-diphenyl-2H-tetrazoliumbromide]) was higher than that of negative control groups for 1 and 4 days’ incubation and had no significant difference for 7 and 11 days’ culture. The results of cell cycle also suggested that the membrane has no negative influence on cell division. The nHA/PA66 membranes were then implanted into subcutaneous sites of nine Sprague Dawley rats. The wounds and implant sites were free from suppuration and necrosis in all periods. All nHA/PA66 membranes were surrounded by a fibrous capsule with decreasing thickness 1 to 8 weeks postoperatively. In conclusion, the results of the in vitro and in vivo studies reveal that nHA/PA66 membrane has excellent biocompatibility and indicate its use in guided tissue regeneration (GTR) or GBR.

Characterization and cytocompatibility of surface modified polyamide66.

The chemical modification of polyamide66 (PA66) membrane by graft polymerization with methacrylic acid (MAA) was initiated under ultraviolet light. Subsequently, covalent immobilization of bioactive surface was obtained by coupling gelatin to the MAA graft chains with the aid of a water-soluble carbodiimide (WSC). The existence of carboxyl groups grafted on PA66 surface was verified quantitatively by UV-vis spectroscopy. The chemical composition, surface topography, and wettability were investigated by Fourier transform infrared (FTIR) technique, X-ray photoelectron spectroscopy, atomic force microscopy, and water contact angle (WCA) measurement. Results showed that the WCA changed from the original value of 67.5 degrees to the minimum value of 30 degrees after grafting with PMAA. Original PA66 displayed a smooth surface morphology [root mean square (RMS) roughness was around 16 nm]. The modified PA66 surface exhibited an increase in roughness (RMS roughness around 21 nm). Simultaneously, the original and modified PA66 membranes were cultured with MG63 cells to investigate their cytocompatibility. The in vitro biological evaluation demonstrated that the immobilization of gelatin on PA66 membrane acted as a good template for the attachment and proliferation of cells. Also, the less toxic reagents and the moderate reaction conditions involved will be very helpful for the introduction of functional groups onto polymer surface.

Physicochemical and Biological Properties of Nano-hydroxyapatite-Reinforced Aliphatic Polyurethanes Membranes

Polymer nano-composite membranes, based on aliphatic biodegradable polyurethane (PU) elastomers and nano-hydroxyapatite (n-HA), were prepared by solvent casting and freeze-drying. The PU matrix was synthesized from 4,4′-dicyclohexylmethane diisocyanate (H12 MDI), poly(ethylene glycol) (PEG), castor oil (CO) and 1,4-butandiol (BDO). The n-HA/PU membranes were characterized by SEM, XRD, IR, TG, mechanical test and in vitro biocompatibility. The results revealed that incorporation of 30 wt% n-HA into the PU matrix increased the tensile strength nearly by 186% and the elongation-at-break by 107% compared to pure PU. The addition of n-HA had the slight positive effect on the thermal stability of PU. Cell culture and MTT assays showed that the incorporation of n-HA into the PU matrix provided a favourable environment for initial cell adhesion, maintained cell viability and cell proliferation. These results suggested that the n-HA/PU composite membrane might be a prospective biodegradable guided bone regeneration (GBR) membrane for future applications.

Biological properties of a biomimetic membrane for guided tissue regeneration: a study in rat calvarial defects

OBJECTIVE The biological properties of nano-hydroxyapatite/polyamide (nHA/PA66) membrane as a guided tissue regeneration barrier were investigated based on a critical-size calvarial defect model. MATERIAL AND METHODS Thirty-six Sprague-Dawley rats were divided into four groups: nHA/PA66 membranes, control treated with expanded polytetrafluoroethylene (e-PTFE) membranes, control treated with PA membranes and blank. Bone regeneration in each group was evaluated using morphological, serological, radiographic and histological techniques at 1, 4 and 8 weeks, respectively, post-operation. RESULTS Slight degradation of nHA/PA66 membranes was observed by a scanning electron microscope (SEM) at 4 and 8 weeks. The serum alkaline phosphatase level and the integral optical density of neo-bone were significantly higher in the nHA/PA66 group than those in the PA group and blank (P<0.05). Radiographic and histological analysis showed a fully closed cranial defect for both the nHA/PA66 group and the e-PTFE group at 8 weeks. No remarkable difference was found between the nHA/PA66 group and the e-PTFE group at each time interval. CONCLUSION nHA/PA66 membrane promoted bone regeneration as effectively as conventional e-PTFE membrane. Based on a rat study, nHA/PA66 membrane provides a promising alternative to e-PTFE membrane due to the absence of requirement for a second surgery.