Efficient Osteogenic Activity of PEEK Surfaces Achieved by Femtosecond Laser-Hydroxylation.

Poly(etheretherketone) (PEEK) is regarded as an attractive orthopedic material because of its good biocompatibility and mechanical properties similar to natural bone. The efficient activation methods for the surfaces of PEEK matrix materials have become a hot research topic. In this study, a method using a femtosecond laser (FSL) followed by hydroxylation was developed to achieve efficient bioactivity. It produces microstructures, amorphous carbon, and grafted -OH groups on the PEEK surface to enhance hydrophilicity and surface energy. Both experimental and simulation results show that our modification leads to a superior ability to induce apatite deposition on the PEEK surface. The results also demonstrate that efficient grafting of C-OH through FSL-hydroxylation can effectively enhance cell proliferation and osteogenic differentiation compared to other modifications, thus improving osteogenic activity. Overall, FSL hydroxylation treatment is proved to be a simple, efficient, and environmentally friendly modification method for PEEK activation. It could expand the applications of PEEK in orthopedics, as well as promote the surface modification and structural design of other polymeric biomaterials to enhance bioactivity.

Modification and evaluation of diatrizoate sodium containing polymethyl methacrylate bone cement.

Polymethyl methacrylate (PMMA) bone cement is now widely used in percutaneous vertebro plasty (PVP) and percutaneous kyphoplasty (PKP). However, studies showed that the radiopacifiers (zirconia, barium sulfate, etc.) added to PMMA will have a negative impact on its use, e.g. barium sulfate will weaken the mechanical properties of bone cement and lead to bone absorption and aseptic loosening. Iodine is an element existing in the human body and has good imaging performance. Iodine contrast agent has been used in clinic for many years and has abundant clinical data. Therefore, using iodine instead of barium sulfate may be a promising choice. In this paper, the effect of different content of diatrizoate sodium (DTA, C11H8I3N2NaO4) on the properties of PMMA was studied and compared with the traditional PMMA bone cement containing 30 wt% barium sulfate. The mechanical properties, setting properties, radiopacity, and biocompatibility of bone cement were evaluated. The compressive strength of PMMA bone cement with 20 wt% DTA can reach 76.38 MPa. DTA released from bone cement up to 14 days accounted for only 2.3% of its dosage. The water contact angle was 62.3°. The contrast of bone cement on X-ray film was comparable to that of bone cement containing 30 wt% barium. The hemolysis rate was lower than 4%, and there was no obvious hemolysis. PMMA with 20 wt% DTA can maintain the relative growth rate of MC3T3-E1 and L929 cells above 80%. The results show that adding 20 wt% DTA into PMMA can obtain good radiopacity while maintaining its mechanical properties, setting properties, and biocompatibility. DTA can be used as a promising candidate material for PMMA bone cement radiopacifier.

A Three-Dimensional Cement Quantification Method for Decision Prediction of Vertebral Recompression after Vertebroplasty.

Objective: Proposing parameters to quantify cement distribution and increasing accuracy for decision prediction of vertebroplasty postoperative complication. Methods: Finite element analysis was used to biomechanically assess vertebral mechanics (n = 51) after percutaneous vertebroplasty (PVP) or kyphoplasty (PKP). The vertebral space was divided into 27 portions. The numbers of cement occupied portions and numbers of cement-endplate contact portions were defined as overall distribution number (oDN) and overall endplate contact number (oEP), respectively. And cement distribution was parametrized by oDN and oEP. The determination coefficients of vertebral mechanics and parameters (R 2) can validate the correlation of proposed parameters with vertebral mechanics. Results: oDN and oEP were mainly correlated with failure load (R 2 = 0.729) and stiffness (R 2 = 0.684), respectively. oDN, oEP, failure load, and stiffness had obvious difference between the PVP group and the PKP group (P < 0.05). The regional endplate contact number in the front column is most correlated with vertebral stiffness (R 2 = 0.59) among all regional parameters. Cement volume and volume fraction are not dominant factors of vertebral augmentation, and they are not suitable for postoperative fracture risk prediction. Conclusions: Proposed parameters with high correlation on vertebral mechanics are promising for clinical utility. The oDN and oEP can strongly affect augmented vertebral mechanics thus is suitable for postoperative fracture risk prediction. The parameters are beneficial for decision-making process of revision surgery necessity. Parametrized methods are also favorable for surgeon's preoperative planning. The methods can be inspirational for clinical image recognition development and auxiliary diagnosis.

The Synergy of Topographical Micropatterning and Ta|TaCu Bilayered Thin Film on Titanium Implants Enables Dual-Functions of Enhanced Osteogenesis and Anti-Infection.

Poor osteogenesis and implant-associated infection are the two leading causes of failure for dental and orthopedic implants. Surface design with enhanced osteogenesis often fails in antibacterial activity, or vice versa. Herein, a surface design strategy, which overcomes this trade-off via the synergistic effects of topographical micropatterning and a bilayered nanostructured metallic thin film is presented. A specific microgrooved pattern is fabricated on the titanium surface, followed by sequential deposition of a nanostructured copper (Cu)-containing tantalum (Ta) (TaCu) layer and a pure Ta cap layer. The microgrooved patterns coupled with the nanorough Ta cap layer shows strong contact guidance to preosteoblasts and significantly enhances the osteogenic differentiation in vitro, while the controlled local sustained release of Cu ions is responsible for high antibacterial activity. Importantly, rat calvarial defect models in vivo further confirm that the synergy of microgrooved patterns and the Ta|TaCu bilayered thin film on titanium surface could effectively promote bone regeneration. The present effective and versatile surface design strategy provides significant insight into intelligent surface engineering that can control biological response at the site of healing in dental and orthopedic implants.

Mussel-inspired hybrid coating functionalized porous hydroxyapatite scaffolds for bone tissue regeneration.

The scaffold for bone tissue engineering should possess proper porosity, adequate mechanical properties, cell affinity for cell attachment, and the capability to bind bioactive agents to induce cell differentiation. In this study, we successfully prepared a porous hydroxyapatite (HA) scaffold that is functionalized by poly(L-lysine)/polydopamine (PLL/PDA) hybrid coating. The PLL/PDA coating takes advantages of the high protein and cell affinity of PDA, as well as the biodegradability of PLL. Therefore, the coating can anchor bone morphogenic protein-2 (BMP2) to the HA scaffold via catechol chemistry under a mild condition so as to protect the bioactivity of BMP2. Meanwhile, the coating can also release BMP2 in a tunable and sustainable manner as the PLL degrades in the physiological environment. The BMP2-entrapped PLL/PDA coating on the HA scaffold can more efficiently promote osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro and induce ectopic bone formation to a much greater level in vivo compared with a bare HA scaffold that delivers BMP2 in a burst manner. All of these results suggest that the PDA-mediated catechol modification of the HA scaffold can be an effective strategy to develop sustainable protein delivery system, and that the PLL/PDA-coated HA scaffold could be a promising candidate for bone tissue engineering applications.

Effect of the Folate Ligand Density on the Targeting Property of Folated-Conjugated Polymeric Nanoparticles.

Targeted drug delivery systems have attracted increasing attention due to their ability for delivering anticancer drugs selectively to tumor cells. Folic acid (FA)-conjugated targeted block copolymers, FA-Pluronic-polycaprolactone (FA-Pluronic-PCL) are synthesized in this study. The anticancer drug paclitaxel (PTX) is loaded in FA-Pluronic-PCL nanoparticles by nanoprecipitation method. The in vitro release of PTX from FA-Pluronic-PCL nanoparticles shows slow and sustained release behaviors. The effect of FA ligand density of FA-Pluronic-PCL nanoparticles on their targeting properties is examined by both cytotoxicity and fluorescence methods. It is shown that FA-Pluronic-PCL nanoparticles indicated better targeting ability than non-targeted PCL-Pluronic-PCL nanoparticles. Furthermore, FA-F127-PCL nanoparticle with 10% FA molar content has more effective antitumor activity and higher cellular uptake than those with 50% and 91% FA molar content. These results prove that FA-F127-PCL nanoparticle with 10% FA molar content can be a better candidate as the drug carrier in targeted drug delivery systems.

Effects of microtopographic patterns on platelet adhesion and activation on titanium oxide surfaces.

This study systematically investigated the effects of microtopographic patterns of titanium oxide on platelet adhesion and activation in order to reveal the mechanisms of interactions between platelet and surface topography. Periodic arrays of groove and pillar patterns with dimensions ranging from submicron to several micrometers were fabricated by photolithography and deep reactive-ion etching on silicon substrates, followed by the sputter deposition of titanium oxide (TiO(2)). Platelet adhesion and activation on TiO(2) patterned surfaces were evaluated by lactate dehydrogenase (LDH) and GMP-140 assays, respectively. The morphology of adherent platelets was examined by scanning electron microscope (SEM). The results showed that the microtopographic patterns were able to effectively manipulate the platelet response by varying geometry and size of patterns. A groove pattern resulted in much higher levels of platelet adhesion and activation than a pillar pattern. The study revealed that a difference in pattern size led to two distinctive modes of platelet adhesion: the "bridging" mode in which platelets can bridge over spacing between adjacent patterns when spacing size is smaller than 1.5 µm; and the "full-contact" mode in which platelets cannot bridge but fully contact the entire surface when spacing size is larger than 3 µm. Our analysis indicates good correlations between platelet behavior and hydrophobicity/wetting anisotropy in "bridging" mode, and effective surface contact area in "full-contact" mode.

Antibacterial coatings of fluoridated hydroxyapatite for percutaneous implants.

Percutaneous orthopedic and dental implants require not only good adhesion with bone but also the ability to attach and form seals with connective tissues and the skin. To solve the skin-seal problem of such implants, an electrochemical deposition method was used to modify the surfaces of metallic implants to improve their antibacterial ability and skin seals around them. A dense and uniform fluoridated calcium phosphate coating with a thickness of about 200 nm was deposited on an acid-etched pure titanium substrate by controlling the current density and reaction duration of the electrochemical process. The as-deposited amorphous fluoridated calcium phosphate transformed to fluoridated hydroxyapatite (FHA) after heat treatment at 600°C in a water vapor environment for 3 h. Both single crystal diffraction patterns and high-resolution transmission electron microscope (HRTEM) images confirmed the phase of the fluoridated calcium phosphate after the heat treatment. The antibacterial activities of FHA coatings were tested against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Porphyromonas gingivalis (P. gingivalis) with the film attachment method. The antibacterial activity of FHA coating is much higher than that of pure hydroxyapatite (HA) coating and acid-etched pure titanium surface. The promising features of FHA coating make it suitable for orthopedic and dental applications.

Characterization and structural analysis of zinc-substituted hydroxyapatites.

The substitution of Zn in hydroxyapatite (HA) crystals was examined via comprehensive characterization techniques. Nanosized HA crystals were synthesized by the wet chemical method in aqueous solutions including various amounts of Zn ions. X-ray fluorescent spectroscopy was used to examine the amount of Zn in the HA precipitates. Scanning electron microscopy and high-resolution transmission electron microscopy were employed to examine the effects of Zn on the morphology and crystal size of the precipitates. Conventional powder X-ray diffraction and the Rietveld refinement method revealed the apatite lattice parameters and phase changes with the inclusion of Zn. The results indicated that Zn ions partially substituted for Ca ions in the apatite structure. They were not simply adsorbed on the apatite surface or in the amorphous phase. The precipitates maintained the apatite phase up to a Zn:(Zn+Ca) ratio of 15-20 mol.% in the solution. Pure HA was well crystallized and the crystals had regular shapes, whereas the Zn-substituted apatite crystals became irregular and formed agglomerates. The lattice parameters, a and c, decreased at a Zn:(Zn+Ca) ratio of 10 mol.%.

Time-of-flight secondary ion mass spectrometry study on the distribution of alendronate sodium in drug-loaded ultra-high molecular weight polyethylene.

The aim of this study was to investigate the drug distribution in ultra-high molecular weight polyethylene (UHMWPE) loaded with alendronate sodium (ALN), which was developed to treat particle-induced osteolysis after artificial joint replacements, since the drug distribution in UHMWPE could play a key role in controlling drug release. A mixture of UHMWPE powder and ALN was dried and hot pressed to prepare UHMWPE loaded with ALN (UHMWPE-ALN). Fourier transform infrared spectroscopy analysis demonstrated that the hot press had no effect on the functional groups of ALN in UHMWPE-ALN. X-ray diffraction indicated that there was no phase change of the UHMWPE after hot pressing. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) spectra revealed the existence of characteristic elements and functional groups from ALN in UHMWPE-ALN, such as Na+, C3H8N+, PO3(-) and PO3H(-). In addition, SIMS images suggested that ALN did not agglomerate in UHMWPE-ALN. A small punch test and hardness test were carried out and the results indicated that ALN did not affect the mechanical properties at the present content level. The present study demonstrated that it was feasible to fabricate the un-agglomerated distributed drug in UHMWPE with good mechanical properties. This ALN loaded UHMWPE would have potential application in clinics.