Journal of Biomaterials Applications

Magnesium alloy is generally accepted as a potential cardiovascular stent material due to its good mechanical properties, biocompatibility, and biodegradability, and has become one of the research hotspots in this field. However, too fast degradation rate and delayed surface endothelialization have been the bottleneck of further application of magnesium alloy stent. In this study, we selected Mg–Zn–Y–Nd, a kind of biodegradable magnesium alloy for cardiovascular stent, and passivated its surface by alkali heat treatment and silane treatment to improve the corrosion resistance, subsequently conjugated Arg–Glu–Asp–Val (REDV) peptide and anti-CD34 to promote endothelial cells adhesion and capture endothelial progenitor cells respectively, further improving surface endothelialization. In addition, the heparin was also immobilized to the Mg–Zn–Y–Nd surface for the consideration of anti-coagulation and anti-inflammation. Systematic material characterization and biological evaluation show that we have successfully developed this composite surface on Mg–Zn–Y–Nd alloy, and achieved multiple functions such as corrosion resistance, promoting endothelialization, and inhibiting platelet/macrophage adhesion.

Selective laser melting used in manufacturing custom-made titanium implants becomes more popular. In view of the important role played by osteoclasts in peri-implant bone resorption and osseointegration, we modified selective laser melting-manufactured titanium surfaces using sandblasting/alkali-heating and sandblasting/acid-etching, and investigated their effect on osteoclast differentiation as well as their underlying mechanisms. The properties of the surfaces, including elements, roughness, wettability and topography, were analyzed. We evaluated the proliferation and morphology of primary mouse bone marrow-derived monocytes, as well as induced osteoclasts derived from bone marrow-derived monocytes, on samples. Then, osteoclast differentiation was determined by the tartrate-resistant acid phosphatase activity assay, calcitonin receptors immunofluorescence staining and the expression of osteoclast-related genes. The results showed that sandblasting/alkali-heating established nanonet structure with the lowest water contact angle, and both sandblasting/alkali-heating and sandblasting/acid-etching significantly decreased surface roughness and heterogeneity compared with selective laser melting. Surface modifications of selective laser melting-produced titanium altered bone marrow-derived monocyte morphology and suppressed bone marrow-derived monocyte proliferation and osteoclastogenesis in vitro (sandblasting/alkali-heating>sandblasting/acid-etching>selective laser melting). These surface modifications reduced the activation of extracellular signal-regulated kinase and c-Jun N-terminal kinases compared to native-selective laser melting. Sandblasting/alkali-heating additionally blocked tumor necrosis factor receptor-associated factor 6 recruitment. The results suggested that sandblasting/alkali-heating and sandblasting/acid-etching modifications on selective laser melting titanium could inhibit osteoclast differentiation through suppressing extracellular signal-regulated kinase and c-Jun N-terminal kinase phosphorylation in mitogen-activated protein kinase signaling pathway and provide a promising technique which might reduce peri-implant bone resorption for optimizing native-selective laser melting implants.

Extracellular matrix loss is one of the early manifestations of intervertebral disc degeneration. Stem cell-based tissue engineering creates an appropriate microenvironment for long term cell survival, promising for NP regeneration. We created a decellularized nucleus pulposus hydrogel (DNPH) from fresh bovine nucleus pulposus. Decellularization removed NP cells effectively, while highly preserving their structures and major biochemical components, such as glycosaminoglycan and collagen II. DNPH could be gelled as a uniform grid structure in situ at 37°C for 30 min. Adding adipose marrow-derived mesenchymal stem cells into the hydrogel for three-dimensional culture resulted in good bioactivity and biocompatibility in vitro. Meanwhile, NP-related gene expression significantly increased without the addition of exogenous biological factors. In summary, the thermosensitive and injectable hydrogel, which has low toxicity and inducible differentiation, could serve as a bio-scaffold, bio-carrier, and three-dimensional culture system. Therefore, DNPH has an outstanding potential for intervertebral disc regeneration.

The purpose of the present study is to modify the polyethylene terephthalate ligament with hydroxyapatite via biomineralization and to investigate its effect on graft-bone healing. After biomineralization of hydroxyapatite, the surface characterization of polyethylene terephthalate ligament was examined by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and water contact angle measurements. The compatibility and osteoinduction, along with the underlying signaling pathway involved of hydroxyapatite-polyethylene terephthalate ligament, were evaluated in vitro. Moreover, a rabbit anterior cruciate ligament reconstruction model was established, and the polyethylene terephthalate or hydroxyapatite-polyethylene terephthalate artificial ligament was implanted into the knee. The micro-computed tomography analysis, histological, and immunohistochemical examination as well as biomechanical test were performed to investigate the effect of hydroxyapatite coating in vivo. The results of scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction showed that the hydroxyapatite was successfully deposited on the polyethylene terephthalate ligament. Water contact angle of the hydroxyapatite-polyethylene terephthalate group was significantly smaller than that of the polyethylene terephthalate group. The in vitro study showed that hydroxyapatite coating significantly improved adhesion and proliferation of MC3T3-E1 cells. The osteogenic differentiation of cells was also enhanced through the activation of ERK1/2 pathway. The micro-computed tomography, histological, and immunohistochemical results showed that biomineralization of hydroxyapatite significantly promoted new bone and fibrocartilage tissue formation at 12 weeks postoperatively. Moreover, the failure load and stiffness in the hydroxyapatite-polyethylene terephthalate group were higher than that in the polyethylene terephthalate group. Therefore, biomineralizaion of hydroxyapatite enhances the biocompatibility and osseointegration of the polyethylene terephthalate artificial ligament, thus promoting graft-bone healing for anterior cruciate ligament reconstruction through the activation of ERK1/2 pathway.

Biomaterials and bone grafts, with the ability of stimulating tissue growth and bone consolidation, have been emerging as very promising strategies to treat bone fractures. Despite its well-known positive effects of biosilicate (BS) on osteogenesis, its use as bone grafts in critical situations such as bone defects of high dimensions or in non-consolidated fractures may not be sufficient to stimulate tissue repair. Consequently, several approaches have been explored to improve the bioactivity of BS. A promising strategy to reach this aim is the inclusion of an organic part, such as collagen, in order to mimic bone structure. Thus, the present study investigated the biological effects of marine spongin (SPG)-enriched BS composites on the process of healing, using a critical experimental model of cranial bone defect in rats. Histopathological and immunohistochemistry analyzes were performed after two and six weeks of implantation to investigate the effects of the material on bone repair (supplemental material-graphical abstract). Histological analysis demonstrated that for both BS and BS/SPG, similar findings were observed, with signs of material degradation, the presence of granulation tissue along the defect area and newly formed bone into the area of the defect. Additionally, histomorphometry showed that the control group presented higher values for Ob.S/BS (%) and for N.Ob/T.Ar (mm²) (six weeks post-surgery) compared to BS/SPG and higher values of N.Ob/T.Ar (mm²) compared to BS (two weeks post-surgery). Moreover, BS showed higher values for OV/TV (%) compared to BS/SPG (six weeks post-surgery). Also, VEGF immunohistochemistry was increased for BS (two weeks post-surgery) and for BS/SPG (six weeks) compared to CG. TGFb immunostaining was higher for BS compared to CG. The results of this study demonstrated that the BS and BS/SPG scaffolds were biocompatible and able to support bone formation in a critical bone defect in rats. Moreover, an increased VEGF immunostaining was observed in BS/SPG.

Ultra-high molecular weight polyethylene has a low X-ray attenuation, hence, the performance of the polyethylene implants used for joint replacements cannot be directly investigated using X-ray-based imaging techniques. In this study, the X-ray attenuation of polyethylene was increased by diffusing an FDA-approved oil-based contrast agent (Lipiodol ultra fluid) into the surface of the samples, and the suitability of this novel radiopaque ultra-high molecular weight polyethylene for clinical applications was examined. Different levels of radiopacity were created by controlling the diffusion parameters, and the level of radiopacity was quantified from computed tomography scans and reported in Hounsfield units. The physical, chemical and tensile properties of the radiopaque ultra-high molecular weight polyethylene were examined and compared to untreated and thermally treated controls. The results of this study confirmed that for the samples treated at 115°C or less the diffusion of the contrast agent did not significantly alter the crystallinity (p = 0.7) or melting point (p = 0.4) of the polyethylene. Concomitantly, the tensile properties were not significantly different from the control samples (p > 0.05 for all properties). In conclusion, the radiopaque ultra-high molecular weight polyethylene treated for less than 18 h at a temperature of 115°C or below is a promising candidate for joint replacement applications as it can be identified in a standard X-ray while retaining the tensile properties of clinically used radiolucent ultra-high molecular weight polyethylene.

Distraction osteogenesis has widespread clinical use in the treatment of large bone defects. Nonetheless, the prolonged consolidation period carries the risk of complications. Magnesium-based materials have been shown to promote bone regeneration in fracture healing both in vitro and in vivo. Here, we investigated whether high-purity magnesium could enhance bone formation in distraction osteogenesis. High-purity magnesium pins were placed into the medullary cavity in the rat distraction osteogenesis model. Results showed that the bone volume/total tissue volume, bone mineral density, and mechanical properties of new callus were significantly higher in the high-purity magnesium group compared to stainless steel and control group (p < 0.01). Histological analyses confirmed improved bone consolidation and vascularization in high-purity magnesium group. Further, polymerase chain reaction-array investigation, Western blot, and immunohistochemical results found that vascular endothelial growth factor and hypoxia inducible factor-1α were highly expressed in the high-purity magnesium group, while Von Hippel–Lindau protein was the opposite (p < 0.01). In conclusion, high-purity magnesium implants have the potential to enhance angiogenesis and bone consolidation in the distraction osteogenesis application, and this process might be via the regulation of Von Hippel–Lindau/hypoxia inducible factor-1α/vascular endothelial growth factor signaling.

Rare earth-doped nanoparticles have been widely used in disease diagnosis, drug delivery, tumor therapy, and bioimaging. Among various bioimaging methods, the fluorescence imaging technology based on the rare earth-doped nanoparticles can visually display the cell activity and lesion evolution in living animals, which is a powerful tool in biological technology and has being widely applied in medical and biological fields. Especially in the band of near infrared (700–1700 nm), the emissions show the characteristics of deep penetration due to low absorption, low photon scattering, and low autofluorescence interference. Furthermore, the rare earth-doped nanoparticles can be endowed with the water solubility, biocompatibility, drug-loading ability, and the targeting ability for different tumors by surface functionalization. This confirms its potential in the cancer diagnosis and treatment. In this review, we summarized the recent progress in the application of rare earth-doped nanoparticles in the field of bioimaging and tumor treatment. The luminescent mechanism, properties, and structure design were also discussed.

With good contrast in T₁ and T₂ weighted imaging as well as low toxicity in 3- (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, this work proposes the cross-linked polydimethylsiloxane colloids as a novel non-ionic contrast agent for gastrointestinal magnetic resonance imaging. The experiments of nuclear magnetic resonance spectra and relaxation show that within the interface of the colloids, there are nuclear Overhauser effect and transient nuclear Overhauser effect (cross-relaxation). Regarding the longitudinal relaxation experiments of CH₂CH₂O segments of Tween 80, a two spins system is found and modeled well by the equation I Z − I 0 =   S 0 ( ( 1 − X )   e − t D 1   − ( 1 + X )   e − t T 1 ) which is deduced based on the transient nuclear Overhauser effect proposed by Solomon. The arbitrary constant X is additionally added with the initial conditions (I_z − I₀) _{t =0} = −2XS₀ and (S_z − S₀) _{t =0} = −2S₀. For the two spins system, D₁ and T₁ are corresponding to longitudinal relaxation times of the bound water and the CH₂CH₂O respectively. Concerning the transverse relaxation experiments of the CH₂CH₂O, they agree with the equation with three exponential decays, defined by three relaxation times, likely corresponding to three mechanisms. These mechanisms possibly are intramolecular and intermolecular dipole–dipole (DD) interactions and scalar coupling. Within the interface, hydrogen bonding causes the positive nuclear Overhauser effect of the CH₂CH₂O’s nuclear magnetic resonance spectra, the transient nuclear Overhauser effect of the CH₂CH₂O’s longitudinal relaxation experiments and the intermolecular dipole–dipole interactions of the CH₂CH₂O’s transverse relaxation experiments.

Polyethylene glycol has been widely investigated for wound healing and dressing applications. Despite its advantages (i.e. great biocompatibility), polyethylene glycol lacks antibacterial activity. For this reason, semi-interpenetrated polymeric networks were prepared by combining a chemically cross-linked polyethylene glycol network with chitosan. The aim of this work was to identify the best amount of chitosan able to improve the antibacterial properties against Staphylococcus aureus. Briefly, the networks were synthesized by a sequential method, adding chitosan in different proportion to the polyethylene glycol. The antibacterial activity was tested following the MGA 0100 of the Pharmacopeia of the United States of Mexico. Fourier-transform infrared with attenuated total reflection spectroscopy, scanning electron microscopy and swelling behavior PBS at 37° C and room temperature were also performed to characterize the polymeric networks. The results showed that PC-2% was able to inhibit the bacterial growth of Staphylococcus aureus even more than Fosfomycin antibiotic. The networks showed cylindrical pores of different sizes (50–100 µm). The maximum swelling of all the networks was achieved in PBS at 37°C (>315%). Free hemoglobin and hemolysis assays were also evaluated to know the compatibility with erythrocytes. Human dermal fibroblasts were used to evaluate direct cytotoxicity. Therefore, the produced gels exerted interesting antibacterial activity and showed good biocompatibility properties.