Proliferation Of Osteoblast-like Cells Research Articles

Investigation of a new implant surface modification using phosphorylated pullulan.

Various implant surface treatment methods have been developed to achieve good osseointegration in implant treatment. However, some cases remain impossible to treat with implants because osseointegration is not obtained after implantation, and the implants fail. Thus, this study focused on phosphorylated pullulan because of its adhesiveness to titanium (Ti) and bone, high biocompatibility, and early replacement with bone. In this study, the response of bone-related cells to phosphorylated pullulan was evaluated to develop a new surface treatment method. Saos-2 (human osteosarcoma-derived osteoblast-like cells), MC3T3-E1 (mouse calvaria-derived osteoblast-like cells), and RAW264.7 (mouse macrophage-like cells) were used. In evaluating cellular responses, phosphorylated pullulan was added to the culture medium, and cell proliferation and calcification induction tests were performed. The proliferation and calcification of cells on the surface of Ti disks coated with phosphorylated pullulan were also evaluated. In addition, bone morphogenetic protein-2 (BMP-2), an osteogenic factor, was used to evaluate the role of phosphorylated pullulan as a drug carrier in inducing calcification on Ti disks. Phosphorylated pullulan tended to promote the proliferation of osteoblast-like cells and the formation of calcification on Ti disks coated with phosphorylated pullulan. Ti disks coated with phosphorylated pullulan loaded with BMP-2 enhanced calcification. Phosphorylated pullulan inhibited osteoclast-like cell formation. These results are due to the properties of phosphorylated pullulan, such as adhesiveness to titanium and drug-loading function. Therefore, phosphorylated pullulan effectively promotes bone regeneration when coated on titanium implants and is useful for developing a new surface treatment method.

Bio-response of copper-magnesium co-substituted mesoporous bioactive glass for bone tissue regeneration.

Mesoporous bioactive glass (MBG) is widely acknowledged in bone tissue engineering due to its mesoporous structure, large surface area, and bioactivity. Recent research indicates that introduction of metallic ions has beneficial impacts on bone metabolism and angiogenesis. Thus, the features of MBG can be modified by incorporating combinations of ions, such as magnesium (Mg) and copper (Cu), which can play a considerable role in bone formation, influencing angiogenesis, osteogenesis, as well as antibacterial properties. In this study, Mg and Cu were co-doped for the first time (in a ratio of 1 : 1) in 80SiO2-5P2O5-(15 - 2x)CaO-xMgO-xCuO glass composition with x = 0, 0.5, 1, and 2 mol%, synthesized using the sol-gel and evaporation-induced self-assembly method. X-ray diffraction analysis confirmed the amorphous nature of the powders, while inductively coupled plasma-optical emission spectrometry verified the existence of dopant ions in the respective amounts. The nitrogen sorption method indicated the formation of uniform cylindrical mesopores which are open at both ends and a high surface area of the powders. TEM images show fringes, indicating an ordered mesoporous structure in all MgCu co-doped systems. In vitro bioactivity was observed in all MBG powders, confirmed by the formation of an apatite phase when placed in simulated body fluid (SBF). Flake-like microstructure characteristics of HAp crystals found on the surface of MBG powders were visualized using FESEM. Cytotoxicity tests at lower concentrations (0.1 and 1 wt/vol%) of co-doped 2MC MBG (co-doping up to 2 mol%) showed cell proliferation and viability of osteoblast-like MG-63 cells and normal human dermal fibroblast (NHDF) cells similar to the basic glass 80S. Antibacterial study of MBG pellets showed an increment in the zone of inhibition with the sequential addition of doping ions. The turbidity measurement of bacterial cultures revealed that the optimal concentration for effectively inhibiting bacterial growth was 1 wt/vol% (i.e., 10 mg mL-1) concentration of MBG extracts. The result suggested that the incorporation of Mg and Cu ions in MBG in lower concentrations of up to 2 mol% can be useful in bone regeneration owing to bioactivity, cell proliferation, and antibacterial characteristics.

Electrochemical Deposition of Copper on Bioactive Porous Titanium Dioxide Layer: Antibacterial and Pro-Osteogenic Activities.

Ti surfaces must exhibit antibacterial activity without cytotoxicity to promote bone reconstruction and prevent infection simultaneously. In this study, we employed a two-step electrochemical treatment process, namely, microarc oxidation (MAO) and cathodic electrochemical deposition (CED), to modify Ti surfaces. During the MAO step, a porous TiO2 (pTiO2) layer with a surface roughness of approximately 2.0 μm was generated on the Ti surface, and in the CED step, Cu was deposited onto the pTiO2 layer on the Ti surface, forming Cu@pTiO2. Cu@pTiO2 exhibited a similar structure, adhesion strength, and crystal phase to pTiO2. Moreover, X-ray photoelectron spectroscopy (XPS) confirmed the presence of Cu in Cu@pTiO2 at an approximate concentration of 1.0 atom %. Cu@pTiO2 demonstrated a sustained release of Cu ions for a minimum of 28 days in a simulated in vivo environment. In vitro experiments revealed that Cu@pTiO2 effectively eradicated approximately 99% of Staphylococcus aureus and Escherichia coli and inhibited biofilm formation, in contrast to the Ti and pTiO2 surfaces. Moreover, Cu@pTiO2 supported the proliferation of osteoblast-like cells at a rate comparable to that observed on the Ti and pTiO2 surfaces. Similar to pTiO2, Cu@pTiO2 promoted the calcification of osteoblast-like cells compared with Ti. In summary, we successfully conferred antibacterial and pro-osteogenic activities to Ti surfaces without inducing cytotoxic effects or structural and mechanical alterations in pTiO2 through the application of MAO and CED processes. Moreover, we found that the pTiO2 layer promoted bacterial growth and biofilm formation more effectively than the Ti surface, highlighting the potential drawbacks of rough and porous surfaces. Our findings provide fundamental insights into the surface design of Ti-based medical devices for bone reconstruction and infection prevention.

Effect of Low-Level Laser Irradiation (810 nm) on the Proliferation and Differentiation of Osteoblast-Like Cells Cultured on SLA Titanium Discs Exposed to a Peri-implantitis Environment.

Introduction: Elimination of inflammation and re-osseointegration are the major objectives of peri-implantitis therapy. Existing data, however, do not support any decontamination approach. Thus, the present in vitro study aims to assess whether the air-debriding decontamination method with erythritol powder restores the biocompatibility of infected titanium discs and to investigate the potent biomodulatory ability of diode laser (810 nm) irradiation to promote cell proliferation and differentiation of premature osteoblast-like cells (MG63) towards osteocytes. Methods: The experimental groups consisted of cells seeded on titanium discs exposed or not in a peri-implantitis environment with or without biomodulation. Infected discs were cleaned with airflow with erythritol powder. Cell cultures seeded on tricalcium phosphate (TCP) surfaces with or without biomodulation with a laser (810 nm) were used as controls. The study evaluated cell viability, proliferation, adhesion (SEM) at 24, 48 and 72 hours, and surface roughness changes (profilometry), as well as the effects of low-level laser therapy (LLLT) on ALP, OSC, TGF-b1, Runx2, and BMP-7 expression in MG63 cells' genetic profile on days 7, 14, and 21. Results: The MTT assay as well as the FDA/PI method revealed that cell proliferation did not show significant differences between sterile and decontaminated discs at any timepoint. SEM photographs on day 7 showed that osteoblast-like cells adhered to both sterile and disinfected surfaces, while surface roughness did not change based on amplitude parameters. The combination of airflow and LLLT revealed a biomodulated effect on the differentiation of osteoblast-like cells with regard to the impact of laser irradiation on the genetic profile of the MG63 cells. Conclusion: In all groups tested, osteoblast-like cells were able to colonize, proliferate, and differentiate, suggesting a restoration of biocompatibility of infected discs using airflow. Furthermore, photomodulation may promote the differentiation of osteoblast-like cells cultured on both sterile and disinfected titanium surfaces.

Tri-Component Hydrogel as Template for Nanocrystalline Hydroxyapatite Deposition Using Alternate Soaking Method for Bone Tissue Engineering Applications.

Composite hydrogels containing apatite-like particles can act as scaffolds for osteoblast proliferation, with applications in bone tissue engineering. In this respect, porous biocompatible hydrogels were obtained from chitosan, oxidized pullulan, and PVA in different ratios. The stability of the hydrogels was ensured both by covalent bonds between aldehyde groups of oxidized pullulan and free amino groups of chitosan, and by physical bonds formed during freeze-thaw cycles and lyophilization. The deposition of calcium phosphates was performed by alternate soaking of the porous hydrogels into solutions with calcium and phosphate ions, assuring a basic pH required for hydroxyapatite formation. The mineralized hydrogels were characterized using FTIR spectroscopy, scanning electron microscopy, X-ray diffraction, and thermogravimetric analysis, showing that inorganic particles containing between 80 and 92% hydroxyapatite were deposited in a high amount on the pore walls of the polymeric matrix. The composition of the organic matrix influenced the crystallization of calcium phosphates and the mechanical properties of the composite hydrogels. In vitro biological tests showed that mineralized hydrogels support the proliferation of MG-63 osteoblast-like cells to a greater extent compared to pristine hydrogels.

Novel Electroactive Mineralized Polyacrylonitrile/PEDOT:PSS Electrospun Nanofibers for Bone Repair Applications.

Bone defect repair remains a critical challenge in current orthopedic clinical practice, as the available therapeutic strategies only offer suboptimal outcomes. Therefore, bone tissue engineering (BTE) approaches, involving the development of biomimetic implantable scaffolds combined with osteoprogenitor cells and native-like physical stimuli, are gaining widespread interest. Electrical stimulation (ES)-based therapies have been found to actively promote bone growth and osteogenesis in both in vivo and in vitro settings. Thus, the combination of electroactive scaffolds comprising conductive biomaterials and ES holds significant promise in improving the effectiveness of BTE for clinical applications. The aim of this study was to develop electroconductive polyacrylonitrile/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PAN/PEDOT:PSS) nanofibers via electrospinning, which are capable of emulating the native tissue's fibrous extracellular matrix (ECM) and providing a platform for the delivery of exogenous ES. The resulting nanofibers were successfully functionalized with apatite-like structures to mimic the inorganic phase of the bone ECM. The conductive electrospun scaffolds presented nanoscale fiber diameters akin to those of collagen fibrils and displayed bone-like conductivity. PEDOT:PSS incorporation was shown to significantly promote scaffold mineralization in vitro. The mineralized electroconductive nanofibers demonstrated improved biological performance as observed by the significantly enhanced proliferation of both human osteoblast-like MG-63 cells and human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs). Moreover, mineralized PAN/PEDOT:PSS nanofibers up-regulated bone marker genes expression levels of hBM-MSCs undergoing osteogenic differentiation, highlighting their potential as electroactive biomimetic BTE scaffolds for innovative bone defect repair strategies.

Effects of Surface Treatment Method Forming New Nano/Micro Hierarchical Structures on Attachment and Proliferation of Osteoblast-like Cells.

Titanium (Ti) and Ti-based alloys are commonly used in dental implants, and surface modifications of dental implants are important for achieving osseointegration (i.e., direct connection between the implant surface and bone). This study investigated the effect of an eco-friendly etching solution-a hydrogen peroxide-sodium bicarbonate mixture-on the surface properties and contact angles of osteoblast adhesion and proliferation on Ti surfaces. Disk-shaped Ti specimens were prepared using different surface treatments (machining, sandblasting, and sandblasting/acid-etching), and they were immersed in the etching solution and ultrasonically cleaned. Surface characterization was performed using scanning electron microscopy, digital microscopy, contact angle analysis, and X-ray photoelectron spectroscopy. MG-63 osteoblasts were cultured on the specimens, and their adhesion to the specimen surface and proliferation were examined using staining and the MTT assay, respectively. Additional etching with the etching solution caused the formation of nano/micro hierarchical structures, increased surface roughness, and enhanced hydrophilicity. Osteoblast adhesion and proliferation were found to improve on the modified surfaces. The eco-friendly etching method has the potential to enhance the biological properties of Ti implant surfaces and thereby improve dental implant performance.

Characterization of 3D printed biodegradable piezoelectric scaffolds for bone regeneration.

The primary objective of this research was to develop a poly(l-lactic acid)(PLLA) scaffold and evaluate critical characteristics essential for its biologic use as a craniofacial implant. PLLAscaffolds were designed and fabricated using fused deposition modeling technology. The surface morphology and microarchitecture were analyzed using scanning electron microscopy (SEM) and microCT, respectively. Crystallography, compressive modulus, and the piezoelectric potential generated upon mechanical distortion were characterized. Hydrolytic degradation was studied. MG63 osteoblast-like cell proliferation and morphology were assessed. The porosity of the scaffolds was 73%, with an average pore size of 450 µm and an average scaffold fiber thickness of 130 µm. The average compressive modulus was 244 MPa, and the scaffolds generated an electric potential of 25 mV upon cyclic/repeated loading. The crystallinity reduced from 27.5% to 13.9% during the 3D printing process. The hydrolytic degradation was minimal during a 12-week period. Osteoblast-like cells did not attach to the uncoated scaffold but attached well after coating the scaffold with fibrinogen. They then proliferated to cover the complete scaffold by Day 14. The PLLA scaffolds were designed and printed, proving the feasibility of 3D printing as a method of fabricating PLLA scaffolds. The elastic modulus was comparable to that of trabecular bone, and the piezoelectric properties of the PLLA were retained after 3D printing. The scaffolds were cytocompatible. These 3D-printed PLLA scaffolds showed promising properties akin to the natural bone, and they warrant further investigation for bone regeneration.

Hydroxyapatite Double Substituted with Zinc and Silicate Ions: Possibility of Mechanochemical Synthesis and In Vitro Properties

In this study, the mechanochemical synthesis of substituted hydroxyapatite (HA) containing zinc and silicon ions having a chemical formula of Ca10-xZnx(PO4)6-x(SiO4)x(OH)2-x, where x = 0.2, 0.6, 1.0, 1.5, and 2.0, was carried out. The synthesized materials were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and inductively coupled plasma spectroscopy. We found that HA co-substituted with zinc and silicate formed up to x = 1.0. At higher concentrations of the substituents, the formation of large amounts of an amorphous phase was observed. The cytotoxicity and biocompatibility of the co-substituted HA was studied in vitro on Hek293 and MG-63 cell lines. The HA co-substituted with zinc and silicate demonstrated high biocompatibility; the lowest cytotoxicity was observed at x = 0.2. For this composition, good proliferation of MG-63 osteoblast-like cells and an increased solubility compared with that of HA were detected. These properties allow us to recommend the synthesized material for medical applications, namely, for the restoration of bone tissue and manufacture of biodegradable implants.

The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis.

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits associated with CAVD, which could allow the use of antisense oligonucleotides and/or isotype gene therapies for the prevention and/or treatment of CAVD.

Impact of Harvesting Method and Donor Age on the Behavior of Human Osteoblast-Like Cells.

Autogenous particulate bone grafts are being utilized in oral implantology for minor grafting procedures. This study aimed to investigate the influence of the bone-harvesting technique, donor age, and donor site on proliferation and differentiation of human primary osteoblast-like cells in the cell culture. Autogenous bone particles (20 samples) were harvested from the maxilla and mandible during surgery using two different protocols, and two types of particulate bone grafts were collected: bone chips and bone sludge. Bone samples were cultured in growth medium and, after 2 to 3 weeks, the cells that grew from bone grafts were cultured in the normal and osteogenic medium for 0, 4, 7, and 20 days. DNA, alkaline-phosphatase (ALP), calcium-content measurements, and Alizarin red/toluidine blue staining were performed. Data were analyzed by repeated-measures analysis of variance with Bonferroni test. The level of statistical significance was set at 5% (P < .05). Total DNA, ALP, and calcium content were significantly higher for the bone chip samples compared to the bone sludge samples. Total DNA and ALP content were significantly higher for the patients in age group 1 (≤ 60 years) compared to age group 2 (> 60 years) and was significantly higher for mandibular samples than maxillary samples on day 20. However, the calcium measurement showed no significant difference concerning donor age and donor site. Data analysis revealed that harvesting technique (bone chips vs bone sludge), donor age (≤ 60 years vs > 60 years), and donor site (maxilla vs mandible) influenced the osteogenic potential of the collected particulate bone graft. The bone chips were superior in terms of osteogenic efficacy and should be considered a suitable option for particulate bone graft collection.

Investigation on the physical properties and biocompatibility of zirconia-alumina-silicate@diopside composite materials and its in vivo toxicity study in embryonic zebrafish.

Bioceramic materials have a wide range of applications in the biomedical field, such as in the repair of bone defects and dental surgery. Silicate-based bioceramics have attracted biomedical researchers' interest due to their bioactivity and biodegradability. In this study, extended the scope of ZAS utilization in bone tissue engineering by introducing calcium-magnesium-silicate (diopside, CMS) as an interface material aim to develop a machinable bioceramic composite (ZASCMS) by the sol-gel method. The physicochemical characterization, in vitro biological properties and in vivo zebrafish cytotoxicity study of ZAS-based composites as a function of CMS contents, 0, 25, 50, 75 and 100 wt%, were performed. Results showed that the as-prepared ZASCMS possessed porous architecture with well-interconnected pore structure. Results also revealed that the mechanical properties of ZASCMS composite materials were gradually improved with increasing CMS contents. The ZASCMS composites with more than 50 wt% CMS had the highest compressive strength and modulus of 6.78 ± 0.62 MPa and 340.10 ± 16.81 MPa, respectively. Regarding in vitro bioactivities, the composite scaffolds were found to stimulate osteoblast-like UMR-106 cell adhesion, growth, and proliferation. The antibacterial activity of the ZASCMS composite scaffolds was tested against Staphylococcus epidermidis (S. epidermidis) and Escherichia coli (E. coli) also exhibited an antibacterial property. Furthermore, the in vivo studies using embryonic zebrafish were exposed to as-prepared particles (0-500 μg mL-1) and showed that the synthesized ZAS, CMS and ZASCMS composite particles were non-toxic based on the evaluation of survivability, hatching rate and embryonic morphology. In conclusions, our results indicated that the synthesized composite exhibited their biological properties and antibacterial activity, which could well be a promising material with high potential to be applied in orthopaedic and dental tissue engineering.

Laser-Deposited Beta Type Ti-42Nb Alloy with Anisotropic Mechanical Properties for Pioneering Biomedical Implants with a Very Low Elastic Modulus.

Present commercial titanium alloy implants have an elastic modulus higher than 100 GPa, whereas that of the cortical bone is much smaller (17–28 GPa). This elastic modulus mismatch produces a stress shielding effect and the resorption of the bone surrounding the implant. In the present work, a <100> fiber texture is developed in β type Ti-42Nb (wt%) alloy ingots generated by laser-directed energy deposition (LDED) in order to achieve anisotropic mechanical properties. In addition, we demonstrate that laser-deposited β type Ti-42Nb alloy ingots with an intense <100> fiber texture exhibit a very low elastic modulus in the building direction (Ez < 50 GPa) and high yield (σ0.2z > 700 MPa) and tensile (UTSz > 700 MPa) strengths. Laser-deposited Ti-42Nb alloy enhances the osteoinductive effect, promoting the adhesion, proliferation, and spreading of human osteoblast-like cells. Hence, we propose that laser-deposited β type Ti-42Nb alloy is a potentially promising candidate for the manufacturing of pioneering biomedical implants with a very low elastic modulus that can suppress stress shielding.

Investigation of the influence of SrO addition on the bioactivity of CaO[sbnd]Na2O-P2O5-B2O3 glass system

In this work, the role of strontium oxide in the bioactive glasses calcium-sodium-borate was studied to evaluate the bioactivity of the system and the rate of the ion release in Simulated Body Fluid (SBF). Five samples were prepared, with concentration of strontium oxide (SrO) from 0 to 20 wt%, in order to understand how SrO change the glass structure and the ionic leaching process in SBF. Results of density and molar volume, XRD, FTIR, weight loss, pH and cytotoxicity assay were presented and discussed as a function of SrO. The measured pH values of SBF, presented lower values for samples with greater amounts of SrO, suggesting that the increase of SrO in the glasses can reduce the release of the ions in SBF. The fraction of tetracoordinate boron, N4, calculated by FTIR results, increases with the addition of SrO, which shows an increase in the glass connectivity and a decrease of the chemical reactivity. The FTIR spectra and X-ray diffraction results, after immersion in SBF, confirmed the materials bioactivity with the formation of carbonated hydroxyapatite or crystalline calcium phosphate. The samples did not show in vitro cytotoxicity against osteoblast cell line. Also, we highlight that 10SrO sample has induced proliferation of osteoblast-like cells in vitro to all concentrations of glass. These results show that SrO doped calcium-sodium-borate glasses are materials with high rate of bioactivity, low cytotoxicity and reduced dissolution rate of the glasses in an aqueous medium, besides induce cells proliferation and bone tissue growth and their biocompatibility with living tissues.

A study of the interactions between human osteoblast-like cells and polymer composites with functionalized graphene derivatives using 2D correlation spectroscopy (2D-COS)

In response to the growing need for development of modern biomaterials for applications in regenerative medicine strategies, the research presented here investigated the biological potential of two types of polymer nanocomposites. Graphene oxide (GO) and partially reduced graphene oxide (rGO) were incorporated into a poly(ε-caprolactone) (PCL) matrix, creating PCL/GO and PCL/rGO nanocomposites in the form of membranes. Proliferation of osteoblast-like cells (human U-2 OS cell line) on the surface of the studied materials confirmed their biological activity. Fluorescence microscopy was able to distinguish the different patterns of interaction between cells (depending on the type of material) after 15 days of the test run. Raman micro-spectroscopy and two-dimensional correlation spectroscopy (2D-COS) applied to Raman spectra distinguished the nature of cell-material interactions after only 8 days. Combination of these two techniques (Raman micro-spectroscopy and 2D-COS analysis) facilitated identification of a much more complex cellular response (especially from proteins) on the surface of PCL/GO. The presented approach can be regarded as a method for early study of the bioactivity of membrane materials.

Fabrication and in vitro characterization of luffa-based composite scaffolds incorporated with gelatin, hydroxyapatite and psyllium husk for bone tissue engineering

Bone tissue engineering is an emerging technology that has been developed in recent years to address bone abnormalities by repairing, regenerating and replacing damaged/injured tissues. In present work, we report the fabrication and characterization of porous luffa-based composite scaffolds composed of Luffa cylindrica (sponge gourd) powder (LC)/hydroxyapatite (HA), psyllium husk (PH) and gelatin (G) in various combinations (w/v) i.e. 3% LC, 5% LC and control (C) (without luffa powder) by using freeze-drying method. The structural stability of the scaffolds was obtained after chemically crosslinking them with glutaraldehyde (GTA), which was identified via scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The hydrophilic behavior of the samples was quantified by water contact angle measurements. The average pore size of the scaffolds was observed in a range of 20–240 µm. As per the obtained data, the apparent and effective porosities were estimated as ∼57.08 ± 4.38%, ∼50.58 ± 4.09%, ∼59.45 ± 1.60% and 51.37 ± 3.36%, 47.94 ± 4.57% and 53.09 ± 5.45% for 3% LC, 5% LC and control (C) scaffolds, respectively. The scaffolds were found to be noticeably stable for 50 days at 37 °C in a lysozyme solution. The liquid retention capacity of the scaffolds revealed that the luffa-based scaffolds gained lower retention capacity compared to the control (C) scaffold; indicating an increase in scaffold stiffness due to the addition of luffa. Compressive strength study demonstrated that the mechanical stability of the fabricated luffa-based scaffolds got increased significantly from ∼1.5 to ∼9.5 MPa, which is comparable to that of trabecular bone. In addition, proliferation and viability analysis of MG-63 osteoblast-like cells revealed a significant level of cellular compatibility i.e. approaching ∼64% proliferation by 6th day in vitro compared to control. Thus, the obtained results demonstrate that the fabricated novel luffa-based scaffolds exhibit good cytocompatibility, remarkable porosity and excellent mechanical strength comparable to native human bone. Therefore, we anticipate that the developed luffa-based scaffolds could be a promising candidate for bone tissue engineering applications.

Delivery of Bioactive Albumin from Multi-Functional Polyampholyte Hydrogels.

Tissue engineered scaffolds are currently being explored to aid in healing and regeneration of non-union fractures in bone. Additionally, albumin has been demonstrated to provide benefits to healing when applied to injury sites. This paper focuses on delivery of calcium modified, bioactive bovine serum albumin (BSA) from a multi-functional polyampholyte polymer scaffold. First, the inherent nonfouling and conjugation properties of the polyampholyte hydrogel were verified to determine the impact of calcium exposure. The polyampholyte hydrogel delivery platform was then assessed with calcium titrations and osteoblast-like cell (MC3T3-E1) adhesion, proliferation, and viability evaluations. Finally, integrin inhibitors were used to identify the binding mechanisms that mediate cell adhesion to the calcium-modified BSA-conjugated hydrogels. An increase in cell adhesion was observed following calcium exposure up to 0.075 M, although this and higher calcium concentrations affected hydrogel stability and cell growth. BSA exposed to 0.05 M calcium and delivered from polyampholyte hydrogels promoted the most promising viable cell adhesion over 7 days. Cell adhesion to the calcium-modified BSA-conjugated hydrogels appeared to be regulated by arginine-glycine-aspartic acid (RGD) and collagen specific integrins. These results demonstrate that the delivery of calcium modified BSA from an implantable polymer scaffold is promising for bone tissue engineering applications.

Mechanical, corrosion, nanotribological, and biocompatibility properties of equal channel angular pressed Ti-28Nb-35.4Zr alloys for biomedical applications

This study systematically investigated the effect of equal channel angular pressing (ECAP) on the microstructure, mechanical, corrosion, nano-tribological properties and biocompatibility of a newly developed β Ti-28Nb-35.4Zr (hereafter denoted TNZ) alloy. Results indicated that ECAP of the β TNZ alloy refined its microstructure by forming ultrafine grains without causing stress-induced phase transformation, leading to formation of a single β phase. The ECAP-processed TNZ alloy exhibited a compressive yield strength of 960 MPa, and high plastic deformation capacity without fracturing under compression loads. Potentiodynamic polarization tests revealed the higher tendency of ECAP-processed TNZ alloys to form passive oxide films on its surface, which exhibited a lower corrosion rate (0.44±0.07 µm/y) in Hanks’ balanced salt solution compared to its as-cast counterpart (0.71±0.10 µm/y). Nanotribological testing also revealed higher resistance of the ECAP-processed TNZ alloy to abrasion, wear and scratching, when compared to its as-cast counterpart. Cytocompatibility and cell adhesion assessments of the ECAP-processed TNZ alloys showed a high viability (111%) of human osteoblast-like SaOS2 cells after 7 d of culturing. Moreover, the ECAP-processed TNZ alloy promoted adhesion and spreading of SaOS2 cells, which exhibited growth and proliferation on alloy surfaces. In summary, significantly enhanced mechanical, corrosion, and biological properties of ECAP-processed TNZ alloy advocate its suitability for load-bearing implant applications. Statement of significanceEqual channel angular pressing (ECAP) provides a unique combination of enhanced mechanical and functional properties of materials by optimizing their microstructures and phase transformations. This study investigated the mechanical, nano-tribological, corrosion, and biocompatibility properties of a newly developed β Ti-28Nb-35.4Zr (TNZ) alloy processed via ECAP. Our findings indicated that ECAP of the β TNZ alloy refined its microstructure by forming ultrafine grains without causing stress-induced phase transformation. Compared to its as-cast counterpart, ECAP-processed TNZ exhibited significantly enhanced compressive yield strength, plastic deformation capacity, hardness, wear, and corrosion properties. Moreover, in vitro cytocompatibility and cell adhesion studies revealed high cellular viabilities, growth and proliferation of osteoblast-like SaOS2 cells on the ECAP-processed TNZ alloy.

Surface functionalization with copper endows carbonate apatite honeycomb scaffold with antibacterial, proangiogenic, and pro-osteogenic activities.

Osteomyelitis is a potentially devastating inflammatory bone disease that leads to bone destruction and loss. Treatment of osteomyelitis requires the removal of residual bacteria as well as osteogenesis with angiogenesis at the site of treatment. Use of an appropriate amount of copper (Cu) in treatment scaffolds may achieve these goals without the risk of toxicity. In this study, the surface of the carbonate apatite honeycomb scaffold was functionalized with Cu through a dissolution-precipitation reaction. The resulting scaffolds retained the honeycomb structure after immersion in CuCl2 solution, and Cu was precipitated on the surface as libethenite [Cu2(OH)PO4]. The surface Cu concentration was controlled by the concentration of the CuCl2 solution. Scaffolds with a surface Cu concentration of 23.8wt% exhibited antibacterial and cytotoxic effects, whereas those with concentrations of ≤4.6wt% exerted antibacterial effects without negatively affecting the cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like cells. Furthermore, scaffolds with a surface Cu concentration of 4.6wt% Cu inhibited bacterial growth for at least 28days and displayed proangiogenic and pro-osteogenic activities in vivo. These data confirm the success in functionalizing scaffolds with Cu that may be utilized as an innovative osteomyelitis therapy.

A Network Pharmacology-Based Study on Vital Pharmacological Pathways and Targets of Eucommiae Cortex Acting on Osteoporosis

Background Eucommiae Cortex is a Chinese herbal medicine with bone protective effects and treats osteoporosis. This study aimed to explore the pharmacological mechanisms of this complex mixture. Methods The active compounds and disease targets involved in the study were obtained from publicly available websites and databases. Core target genes were identified by protein-protein interaction (PPI) network and topology analysis and mapped to critical components by a “component-target” regulatory network. Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis and Gene Ontology (GO)analysis were performed to analyze the biological processes of target genes. Moreover, we carried out molecular docking, cell experiments, and quantitative real-time PCR to propel the research forward. Results Eucommiae Cortex contained 28 active ingredients and 85 potential targets for antiosteoporosis. PPI networks and topology analysis screened 17 core target genes. The therapeutic mechanism involves a series of biological reactions, including host-virus response, chemical stress, oxidative stress, and cell cycle control. The KEGG enrichment illustrated that the MAPK signaling pathway might play a significant role. The final experiment detected ten genes (EGF, AKT1, JUN, MAPK8, MAPK1, CASP3, FOS, VEGFA, EGFR, and MYC) and three compounds (quercetin, kaempferol, and beta- carotene) in the MAPK pathway. Firstly, the CCK-8 and ALP activity test results showed that three compounds could enhance the proliferation and differentiation of osteoblast-like MC3T3-E1 cells. Secondly, molecular docking confirmed the favorable binding potential. Subsequently, we observed that adding 1∗10−6 mol/L quercetin, 1∗10−5 mol/L kaempferol, and 1∗10−5 mol/L beta-carotene activated the ERK/JNK cascades and the heterodimer complex AP-1(Fos/Jun) in the MAPK pathway. Conclusion MAPK pathway might provide an essential mechanism for the antiosteoporosis effect of Eucommiae Cortex. Eucommiae Cortex and its active ingredients have the potential to treat osteoporosis.