Search

The promotion of vascular network formation in the early stages of implantation is considered a prerequisite for successful functional bone regeneration.

The biologically inert and excessive elastic modulus of Ti implant surface, as well as the excessive gap between implant and host, will lead to poor bone integration even implant failure. To solve the above problems, in this study, a method for functional Ti implant is reported, in which metal ions-containing bacterial cellulose (BC) coating is introduced in situ on the surface of Ti with complex shapes. Magnesium and strontium ions can be loaded into BC by in situ biosynthesis, which have great effects on the growth of bacteria and the structure of cellulose. In addition, both in vitro and in vivo experiments confirmed that the in situ preparation of functional BC coating on the Ti surface can integrate the operative crevices and promote osteogenesis. This simple and novel method for functional Ti implants has potential application value in clinical bone tissue repair and regeneration.

Diabetes is a universal disease in the world. In the wounds of diabetic individuals, chronic inflammation and an inefficient fibrogenic process hinder the formation and deposition of the ECM, which delays the process of wound healing. To reconstruct the ECM of a diabetic patient's wound, in this work, we designed a pH-responsive "Double H-bonds" (hydrogen bond and hydrazone bond) hyaluronic acid-collagen hydrogel. This hydrogel can be self-gelled quickly in neutral and alkaline environments. But the weakly acidic inflammatory environment of diabetic wounds may accelerate the degradation of the hydrogel and the release of metformin. The

Diffuse large B-cell lymphoma (DLBCL) is a systemic hematological malignancy. Herein, through whole exome sequencing (WES), we found that DLBCL genome changes and expression characteristics are associated with various immune cells. Lenalidomide (Len) is a leading candidate for the immunomodulatory treatment of multiple myeloma in the clinic. Inspired by lenalidomide as an immunomodulatory drug for the treatment of multiple myeloma, we constructed a multifunctional nanoplatform with therapeutic and imaging properties for DLBCL by co-loading lenalidomide and dexamethasone (Dex) with upconversion nanoparticles using a GSH-sensitive linker (named as UCNPs-Len-Dex). In vitro cell experiments proved that the UCNPs-Len-Dex had good biocompatibility and obvious antitumor efficacy. UCNPs-Len-Dex also exhibited excellent anti-tumor efficacy and imaging properties in vivo. RNA sequencing showed that UCNPs-Len-Dex targeted and activated the E3 ligase of CRBN, resulting in IKZF1/3 degradation, which inhibited MYC/BCL6-positive DLBCL and maintained the stability of the immune microenvironment. Therefore, this study provided a new monitoring and therapeutic synergetic strategy for DLBCL.

The blood-brain barrier (BBB) is one of the major limitations of glioblastoma therapy in the clinic. Nanodrugs have shown great potential for glioblastoma therapy. Herein, we purposefully developed a multicomponent self-assembly nanocomplex with very high drug loading content for curing orthotopic glioblastoma with synergistic chemo-photothermal therapy. The nanocomplex consisted of self-assembled pH-responsive nanodrugs derived from amino acid-conjugated camptothecin (CPT) and canine dyes (IR783) coated with peptide Angiopep-2-conjugated copolymer of Ang-PEG-g-PLL. Specifically, the carrier-free nanocomplex exhibited a high drug loading content (up to 62%), good biocompatibility, and effective glioma accumulation ability. Moreover, the nanocomplex displayed good stability and pH-responsive behavior ex vivo. Both in vitro and in vivo results revealed that the nanocomplex could effectively cross the BBB and target glioma cells. Furthermore, the combination of chemotherapy and photothermal therapy of the nanocomplex achieved a better therapeutic effect, longer survival time, and minimized toxic side effects in orthotopic glioblastoma tumor-bearing nude mice. Overall, we modified the chemotherapeutic drug CPT so that it could self-assemble with other molecules into nanoparticles, which providing an alternative for the preparation of the carrier-free nanodrugs. The results highlighted the potential of self-assembly nanodrugs as a novel platform for effective glioblastoma therapy.

Sclerostin is a negative regulator of the Wnt signaling pathway for osteoblast differentiation. In this study, osteoblasts were co-cultured with osteocytes (MLO-Y4 cells) on the surface of sclerostin antibody-conjugated TiO2 nanotube arrays (TNTs-scl). Field emission scanning electron microscopy (SEM), contact angle measurement and confocal laser scanning microscope (CLSM) were employed to characterize the conjugation of sclerostin antibody onto the surface of TiO2 nanotube arrays. The cellular viability and morphology results displayed TNTs-scl (TNT30-scl and TNT70-scl) were beneficial to the growth of MLO-Y4 cells. There was no apparent change in sclerostin gene expression between MLO-Y4 cells grown on TNTs and TNTs-scl. However, TNTs-scl significantly reduced the amount of sclerostin in the medium. In comparison with the control groups, osteoblasts displayed higher differentiation capability when co-cultured with MLO-Y4 cells on the surface TNTs-scl, which was indicated by the ALP activity, mineralization capability as well as expression levels of key proteins in Wnt signaling. This study provides a simple strategy to engineer titanium surface for bone fracture recovery, especially in osteoporotic conditions.

Background The relationship between the solid fuels and the occurrence of pregnancy-induced hypertension (PIH) is inconclusive. Methods A birth cohort study of 10,452 pregnant women without chronic hypertension was conducted from 2010 to 2012 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China. Multivariable logistic regression models were used to assess the relationship. Results Compared to pregnant women using gas as cooking fuel, pregnant women using coal (OR=2.55, 95% CI: 1.85-3.51)and biomass (OR=3.58, 95% CI: 2.29-5.60) were associated with an increased risk of PIH, gestational hypertension (biomass: OR=3.38, 95% CI: 1.68-6.80), and preeclampsia (coal: OR=2.89, 95% CI: 1.98-4.21; biomass: OR=3.38, 95% CI: 1.95-5.84).The relationship between cooking fuel and PIH is modified by maternal age(p

Maintaining the balance between bone formation and bone resorption as well as reducing bacterial infection are two major challenges for titanium (Ti) when it is used as the implant in orthopedic surgery. Because of its excellent properties, including anti-inflammatory, antimicrobial, promoting osteoblasts, and inhibiting osteoclasts growth, lactoferrin (LF) is a potential bioactive molecule for surface modification of Ti implants. Inspired by the highly hierarchical structure of natural bone tissue, in this work, a polydopamine-assisted hydroxyapatite and lactoferrin multilayer structure (PDA-HA-LF) was prepared onto the Ti substrate surface by a biomimetic approach and spin-assisted layer-by-layer (LBL) assembly technique. Meanwhile, its capabilities on regulation of bone balance and antibacterial properties were measured with cell experiments and antimicrobial activity in vitro. Furthermore, the regulation theory was investigated by qPCR and theoretical simulation. The results showed that the biological properties of LF are highly correlated with its concentration. High concentration of LF was toxic to osteoblasts but has obvious effects on inhibition of osteoclasts and bacteria (

Due to their simple crystal structures, one-dimensional hydroxyapatite (HA) nanostructures are easily to be applied to understand the fundamental concepts about the influences of HA dimensionality on physical, chemical, and biological properties. So, in this work, three typical HA one-dimensional nanostructures, HA nanotubes, HA nanowires, and HA nanospheres, were prepared, whose theoretical structures were built also. in vitro cytocompatibility test proved that, contrasting with TCPS, HA one-dimensional nanostructures had certain degree of cytotoxicity because HA nanostructures increase the generation of intracellular reactive oxygen species (ROS) and intracellular calcium. Theoretical simulation indicated that HA nanosphere has higher intracellular ROS generation and lower ROS storage amount than HA nanowire and HA nanotube, which were the possible reasons for its stronger cytotoxicity. Among these typical one-dimensional nanostructures, owing to higher drug storage amount and sustained delivery ability, HA nanotube was more potential application in orthopedics. The tubular structure of HA nanotubes could be used as reservoirs for small molecule drugs or growth factors. The cytocompatibility of HA nanostructures can be improved obviously when they were produced into two-dimensional structures. The prepared multilayer structure can simulate lamellar structures of Harvard system and enhance the cytocompatibility of Ti substrate. Therefore, the method used in this work is a prospective method to improve the inherently bio-inert of Ti when used in hard tissue repairing.

To develop biomaterials for inducing osteogenic and angiogenic differentiation of mesenchymal stem cells (MSCs) is crucial for bone repair. In this study, we employed titania nanotubes (TNT) as drug nanoreservoirs to load deferoxamine (DFO), and then deposited chitosan (Chi) and gelatin (Gel) multilayer as coverage structure via layer-by-layer (LBL) assembly technique, resulting in TNT-DFO-LBL substrates. Scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle measurements were employed to characterize the physical and chemical properties of the substrates. The results proved the successful fabrication of multilayer coating on TNT array. DFO released from the TNT arrays in a sustained manner. The drug-device combination titanium (Ti) substrates positively improved the adhesion, proliferation, osteogenic/angiogenic differentiation of MSCs and mediated the growth behavior of human umbilical vein endothelial cells (HUVECs). Moreover, the TNT-DFO-LBL substrates up-regulated osteogenic and angiogenic differentiation related genes expression of MSCs by activating HIF-1α signaling pathway. The approach presents here has a potential impact on the development of high quality Ti-based orthopedic implants.

The inherent bioinertness and potential bacterial infection risk are the two leading causes for Ti implant failure. To improve osseointegration and antibiosis, in this work, a novel antimicrobial osteogenic growth peptide was first synthesized by conjugating osteogenic growth peptide (OGP) and ciprofloxacin (CIP). Then, the synthetic antimicrobial peptide was immobilized onto Ti implant surface for chemoselective binding via the amide reaction. Thereafter, the capabilities of modified Ti implant on osseointegration and antibiosis were measured with cell experiments and antimicrobial activity in vitro. The results showed that antimicrobial osteogenic growth peptide (OGP-CIP) was successfully prepared and grafted onto Ti implant surface. Moreover, the antimicrobial peptide-modified Ti implants could promote osteoblasts spreading and osteodifferentiation compared with unmodified Ti substrates. Meanwhile, in vitro bacteria studies (Staphylococcus aureus and Escherichia coli) proved that the antibacterial property of antimicrobial peptide functionalized Ti implant was improved obviously. The method used in this work is a feasible and promising strategy to win the race against invading bacteria and accelerate bone integration in orthopedic implantation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3021-3033, 2018.

Surface topography had been identified as a crucial property that affects osseointegration; thus, topographical modification was the most frequently adopted technique in titanium-based implant research. In this study, ethyl cellulose was employed as an additive to construct a zinc-incorporated nano-network layer onto a titanium surface by the sequential treatments of spin-coating, high-temperature calcination, and alkali heat corrosion. SEM results showed that 20 mg/mL of ethyl cellulose was optimal to fabricate a relatively flat porous coating, and the ideal nano-network structures formed by only 4 h of corrosion. Other results of XPS and ICP further proved that zinc ions were successfully incorporated into the final samples (Ti-Zn0.1, Ti-Zn0.3, and Ti-Zn0.4). Moreover, the in vitro cellular (e.g., CCK-8, ALP, mineralization) and bacterial assays presented that Ti-Zn0.3 substrates not only had the greatest proliferation and differentiation capacities for osteoblasts but also possessed relatively strong antibacterial abilities for both Escherichia coli and Staphylococcus aureus. This study provided a new way to rapidly construct the pro-osteogenesis and antibacterial nano-network structures on titanium surfaces for orthopedic application.

Selective laser melting (SLM) is one of the three-dimensional (3D) printing techniques that manufacturing versatile porous scaffolds with precise architectures for potential orthopedic application. To understand how the pore sizes of porous Ti6Al4V scaffolds affect their biological performances, we designed and fabricated porous Ti6Al4V implants with straightforward pore dimensions (500, 700, and 900 µm) via SLM, termed as p500, p700, and p900 respectively. The morphological characteristics of Ti6Al4V scaffolds were assessed showing that the actual pore sizes of these scaffolds were 401 ± 26 µm, 607 ± 24 µm, 801 ± 33 µm, respectively. The mechanical properties of Ti6Al4V scaffolds were also evaluated showing that they were comparable to that of bone tissues. Meanwhile, the effect of pore size on biological responses was systematically investigated in vitro and in vivo. It was verified that 3D printing technique was able to fabricate porous Ti6Al4V implants with proper mechanical properties analogous to human bone. The in vitro results revealed that scaffolds with appropriate pore dimension were conducive to cell adhesion, proliferation and early differentiation. Furthermore, the porous Ti6Al4V scaffolds were implanted into the rabbit femur to investigate bone regeneration performance, the in vivo experiment showed the p700 sample was in favor of bone ingrowth into implant pores and bone-implant fixation stability. Taken together, the biological performance of p700 group with actual pore size of about 600 µm was superior to other two groups. The obtained findings provide basis to individually design and fabricate suitable porous Ti6Al4V with specific geometries for orthopedic application.

Type I co-activator-associated arginine methyltransferase 1 (CARM1) and type II protein arginine methyltransferase 5 (PRMT5) are highly expressed in multiple cancers including liver cancer and their overexpression contributes to poor prognosis, thus making them promising therapeutic targets. Here, we evaluated anti-tumor activity of ribavirin in hepatocellular carcinoma (HCC). We found that ribavirin significantly inhibited the proliferation of HCC cells in a time- and dose-dependent manner. Furthermore, ribavirin suppressed the growth of subcutaneous and orthotopic xenograft of HCC in mice, decreased vascular endothelial growth factor (VEGF) and peritoneal permeability to reduce ascites production, and prolonged the survival of mice in HCC ascites tumor models. Mechanistically, ribavirin potently down-regulated global protein expression of CARM1 and PRMT5, and concurrently decreased accumulation of H3R17me2a and H3R8me2s/H4R3me2s. However, ribavirin did not affect the activity and mRNA levels of both CARM1 and PRMT5 in vivo and in vitro HCC cells. In addition, our ChIP results shown that ribavirin inhibited CARM1 which in turn decreased the H3R17me2a, binds to the eukaryotic translation initiation factor 4E (eIF4E) and VEGF promoter region, and reduced the relative mRNA expression level of eIF4E and VEGF in HCC cells. Our findings suggested a potential therapeutic strategy for patients with HCC through inhibition of the abnormal activation/expression of both CARM1 and PRMT5.

Effective and fast osseointegration is important for the survival of titanium-based orthopaedic implants. Previous studies confirmed that topographic features combined with inorganic ions showed positive effects on the biological functions of osteoblastic cells. In this study, we report an approach for fabricating Fe-incorporated micro-nano hierarchical structures on titanium substrates, which was realized by dual acid etching and subsequent hydrothermal treatment. The surface morphology, surface chemistry and wettability of the titanium substrates were characterized using scanning electron microscopy, X-ray photoelectron spectroscopy and contact angle measurements, respectively. The Fe-incorporated micro-nano hierarchical titanium substrates were probed to be biocompatible and positively improved protein adsorption, cell proliferation and cell differentiation of osteoblasts in vitro. Furthermore, the Fe-incorporated titanium substrates significantly enhanced the expressions of osteogenic genes (such as Runx2, Col I, OPN, and OCN), which were attributed to the synergistic effects of micro-nano structures and Fe ions. More importantly, the Fe-incorporated titanium implants with micro-nano hierarchical structures promoted new bone formation in vivo. This study provides an alternative for the development of orthopaedic implants with improved osseointegration for potential clinical applications.

Antibacterial titanium implants used in orthopedic and oral tooth repair have been widely researched for reducing the occurrence of second replacement operation. Although possessing a good antibiosis effect, the traditional methods have poor biocompatibility and even may cause damage to the body. Especially for loading antibiotic, after killing pathogenic bacteria, the residual antibacterial drugs may hinder the implant-tissue binding. Here, we develop a novel strategy for Ti implant based on photolithography, which can achieve the near-infrared (NIR) light-controlled antimicrobial agents loading, releasing, and clearing. A grid-like stamp of antibacterial complex and osteogenic growth peptide (OGP) were successfully prepared onto lanthanide-doped upconverting nanoparticles (UCNPs) decorated Ti substrate by selectively flicking antimicrobial agents away and replacing them with OGP. In vitro antibacterial evaluation and cell experiments proved that the modified Ti substrate (Ti-LA/OGP) exerts excellent antibacterial ability, as well as outstanding osteoinductive abilities for osteoblasts adhesion and differentiation. When implanted in infection models, Ti-LA/OGP possesses high antibacterial property at the early stage of implantation. After the success of antibiosis, irradiated with NIR light to remove the residual antibacterial agents, the osteogenesis of Ti-LA/OGP implants can be improved obviously. Moreover, this work may provide a promising strategy for the dynamic study of orthopedic application.

In this work, we report a novel strategy to construct cell pattern on titanium substrates by using upconversion nanoparticles (UCNPs). When irradiating with a NIR laser (980 nm) through a photomask, the UCNPs could transfer NIR light into UV light in situ, which results in photocleavage and detachment of unsheltered cells for the formation of cell pattern. This work provides a new perspective for the application of UCNPS in biomedical field.

To improve the biological performance of titanium substrates, a bioactive multilayered structure of chitosan/gelatin pair, containing zinc ions, was constructed via a layer-by-layer self-assembly technique. The successful preparation of zinc ions incorporated multilayer films was demonstrated by scanning electron microscopy, X-ray photoelectron spectroscopy, and contact angle measurements, respectively. The biological behaviors of osteoblasts adhered to modified Ti substrates were investigated in vitro via cytoskeleton observation, cell viability measurement, and alkaline phosphatase activity assay. The cytocompatibility evaluation verified that the present system was capable of promoting the growth of osteoblasts. In addition, Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria were used to evaluate antibacterial property of modified Ti substrates. Bacterial adhesion and viability assay confirmed that Zn-loaded multilayer films were able to inhibit the adhesion and growth of bacteria. The approach presented here affords an alternative to reduce bacterial infection and promote osteoblast growth for titanium-based implants.

After bone tumor resection, the large bony deficits are commonly reconstructed with Ti-based metallic endoprosthesis, which provide immediate stable fixation and allow early ambulation and weight bearing. However, when used in osteosarcoma resection, Ti implant-relative infection and tumor recurrence were recognized as the two critical factors for implantation failure. Hence, in this work, a novel zinc oxide nanoparticle decorating with naringin was prepared and immobilized onto Ti substrate. The drugs delivery profiles proved that in the bacterial infection and Warburg effect of osteosarcoma-induced acidic condition, naringin and Zn2+ can be released easily from the functional Ti substrate. The anti-osteosarcoma and antibacterial assay showed the delivered naringin and Zn2+ can induce a remarkable increase of oxidative stress in bacteria (Escherichia coli and Staphylococcus aureus) and osteosarcoma (Saos-2 cells) by producing reactive oxygen species (ROS). Accumulation of ROS results in damage of bacterial biofilm and bacterial membrane, leading to the leakage of bacterial RNA and DNA. Meanwhile, the increase of ROS induces osteosarcoma cell apoptosis by activating ROS/extracellular signal-regulated kinase signaling pathway. Furthermore, in vitro cellular experiments, including cell viability, alkaline phosphatase activity, collagen secretion, extracellular matrix mineralization level, indicated that the functional Ti substrate exhibited great potential for osteoblasts proliferation and differentiation. Hence, this study provides a simple and promising strategy of developing multifunctional Ti-based implants for the reconstruction of large bony after osteosarcoma resection.

In this study, a simple one-step co-deposition process was introduced to fabricate antibacterial surfaces for synthetic materials via UV-inducing dopamine polymerization combined with in situ formation of Ag nanoparticles. The successful formation of a composite coating was demonstrated by scanning electron microscopy. Antibacterial experiments including antibacterial rate test and bacteria adhesion were evaluated in vitro. The results confirmed the excellent antibacterial property of this surface modification process. In conclusion, the approach presented here provides a simple and effective approach to construct antibacterial surfaces for synthetic materials to meet the requirements of daily life and industry application.

Anodization is a promising method to change the topography and wettability of titanium (Ti) implant. The formed TiO2 nanotubes (TiNTs) arrays could enhance the biological properties of Ti implants. In this study, to investigate the possibility of TiNTs arrays on a Ti implant surface as nano-reservoirs for small molecular drugs when using in orthopedic and dental prosthesis, TiNTs on a Ti implant surface were prepared. Then, aspirin and/or vitamin C were loaded into TiNTs as model drugs. Meanwhile, low molecular weight polylactic acid (PLA, Mw=3000) was synthesized and loaded alternately along with aspirin or vitamin C. The release rates of aspirin and vitamin C with/or without PLA loading were investigated by using a UV-Vis spectrometer. The results showed that when loading without PLA, drugs released quickly with presence of burst release. However, when loading with PLA, the cumulative release duration of aspirin and vitamin C was prolonged to over 240h. Molecular dynamics (MD) simulation and dissipative particle dynamics (DPD) simulation results proved that when loading with PLA, PLA molecules aggregated gradually and formed clusters or micelles in these nanotubes. Meanwhile, drug molecules were captured and distributed inside the PLA matrix, which retarding the release of drugs. Only when PLA micelles degrade gradually in body fluid, drugs could be released slowly from nanotubes. These knowledge laid ground basis for the following biological experiments.

To enhance long-term survival of titanium implants in patients with osteoporosis, chitosan/gelatin multilayers containing bone morphogenetic protein 2(BMP2) and an antiosteoporotic agent of calcitonin (CT) are deposited on the Ti6Al4V (TC4) implants through layer-by-layer (LBL) electrostatic assembly technique. Here, the obtained titanium alloy implant (TC4/LBL/CT/BMP2) can regulate the release of loaded calcitonin and BMP2 agents in a sustaining manner to accelerate the bone formation and simultaneously inhibit bone resorption. In vitro results show that the bone-related cells on TC4/LBL/CT/BMP2 present the lowest production level of tartrate resistant acid phosphatase (TRAP) but the highest (p < 0.05) level of alkaline phosphatase (ALP) activity, osteocalcin production, mineralization capacity and osteoblast-related gene expression among all groups after treatment for 7 or 21 days, respectively. Besides, in vivo studies of micro-CT analysis, routine histological and immunohistochemical analysis also collectively demonstrate that the TC4/LBL/CT/BMP2 implant can dramatically promote the formation and remodeling of new bone in osteoporotic rabbits after implantation for 30 days and 90 days, respectively. In vivo push-out testing further confirms that the TC4/LBL/CT/BMP2 implant has the highest (p < 0.01) interfacial shear strength and favorable bone-implant osseointegration. Overall, this study establishes a simple and profound methodology to fabricate a biofunctional TC4 implant for the treatment of local osteoporotic fractures in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1437-1451, 2016.

The immune response to an orthopedic implant is closely related to the nearby bone metabolism balance. To modify titanium (Ti) substrates and accordingly regulate the balance between osteoclast activation and osteoblast differentiation, a multifunctional peptide OGP-NAC was synthesized via conjugating an osteogenic growth peptide (OGP) with N-acetylcysteine (NAC). Then, the synthesized peptide was employed to functionalize Ti substrates and the response of both osteoblasts and osteoclasts was investigated in vitro. The results showed that OGP-NAC was successfully prepared and immobilized onto Ti substrate surfaces. Thereafter, studies on introducing RAW 264.7 cells (one kind of monocyte macrophage responsible for immune responses) to osteoclasts demonstrated that the peptide modified Ti surface could inhibit RAW 264.7 cells from secreting important inflammatory cytokines (TNF-α and IL-1β), and suppress the activation of MAPK, NF-κB and NFAT c1, which are important transcription factors for osteoclastogenesis. Meanwhile, the modified surface promoted osteoblast spreading, proliferation and differentiation. The study offers a feasible strategy to mediate the balance between osteoclast activation and osteoblast differentiation, having great potential for improving osseointegration of an orthopedic implant.

Sclerostin is a negative regulator of the Wnt signaling pathway for osteoblast differentiation. In this study, osteoblasts were co-cultured with osteocytes (MLO-Y

Bone defects/fractures are common in older people suffering from osteoporosis. Traditional hydroxyapatite (HA) materials for osteoporotic bone repair face many challenges, including limited bone formation and aseptic loosening of orthopedic implants. In this study, a new multifunctional HA is synthesized by spontaneous assembly of alendronate (AL) and Fe3O4 onto HA nanocrystals for osteoporotic bone regeneration. The chemical coordination of AL and Fe3O4 with HA does not induce lattice deformation, resulting in a functionalized HA (Func-HA) with proper magnetic property and controlled release manner. The Func-HA nanocrystals have been encapsulated in polymer substrates to further investigate their osteogenic capability. In vitro and in vivo evaluations reveal that both AL and Fe3O4, especially the combination of two functional groups on HA, can inhibit osteoclastic activity and promote osteoblast proliferation and differentiation, as well as enhance implant osseointegration and accelerate bone remodeling ...

The inherent bioinertness and potential bacterial infection risk are the two leading causes for Ti implant failure. To improve osseointegration and antibiosis, in this work, a novel antimicrobial osteogenic growth peptide was first synthesized by conjugating osteogenic growth peptide (OGP) and ciprofloxacin (CIP). Then, the synthetic antimicrobial peptide was immobilized onto Ti implant surface for chemoselective binding via the amide reaction. Thereafter, the capabilities of modified Ti implant on osseointegration and antibiosis were measured with cell experiments and antimicrobial activity in vitro. The results showed that antimicrobial osteogenic growth peptide (OGP-CIP) was successfully prepared and grafted onto Ti implant surface. Moreover, the antimicrobial peptide-modified Ti implants could promote osteoblasts spreading and osteodifferentiation compared with unmodified Ti substrates. Meanwhile, in vitro bacteria studies (Staphylococcus aureus and Escherichia coli) proved that the antibacterial property of antimicrobial peptide functionalized Ti implant was improved obviously. The method used in this work is a feasible and promising strategy to win the race against invading bacteria and accelerate bone integration in orthopedic implantation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3021-3033, 2018.

The kinetic parameters for the co-combustion of municipal solid waste incineration fly ash, sawdust, and shale have been determined by a sync analyzer, aiming to simulate the manufacture of lightweight aggregates process. Experiments were carried out with about each 10-mg samples at different heating rates in air and argon atmospheres, respectively. The results indicate that behaviors of the mixture can be broadly divided into four separate events. The total mass loss reached the maximum at 20 K·min–1. There appears to be no unanimous formula of the degree of the total mass loss in different gas atmospheres.

To mimic extracellular microenvironment of endothelial cell, a bioactive multilayered structure of gelatin/chitosan pair, embedding with vascular endothelial growth factor (VEGF), was constructed onto NiTi alloy substrate surface via a layer-by-layer assembly technique. The successful fabrication of the multilayered structure was demonstrated by scanning electron microscopy, atomic force microscopy, contact angle measurement, attenuated total reflection-fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively. The growth behaviors of endothelial cells on various NiTi alloy substrates were investigated in vitro. Cytoskeleton observation, MTT assay, and wound healing assay proved that the VEGF-embedded multilayer structure positively stimulated adhesion, proliferation and motogenic responses of endothelial cells. More importantly, the present system promoted the nitric oxide production of endothelial cells. The approach affords an alternative to construct extracellular microenvironment for improving surface endothelialization of a cardiovascular implant.

In this study, dextran sulfate (DS)/chitosan (CHI) multilayer films were fabricated on TiN-coated NiTi alloy to reduce Ni ion release and improve biocompatibility. The successful formation of TiN coating and DS/CHI multilayer films was demonstrated by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Inductively coupled plasma mass spectrometry (ICP-MS) test showed that the Ni ion release from NiTi alloy significantly decreased after surface modification. Cytocompatibility including osteoblasts adhesion and differentiation function was evaluated in vitro. The results suggest that this surface modification process is beneficial for osteoblasts growth on NiTi alloy substrate. The approach presented here provides an attractive way for surface modification of NiTi alloy to meet the requirements of biomedical applications.

In this study, we report the influence of titania nanotubes (TiNTs) dimensions on the adsorption of collagen (COL) and fibronectin (FN), and its subsequent effect on the growth of osteoblasts. TiNTs with different diameters of around 30 and 100 nm were prepared with anodization. The adsorption profiles of proteins and cell behaviors were evaluated using spectrophotometric measurement, immunofluorescence staining, cell viability, and cytoskeleton morphology, respectively. The results showed that although the growth of osteoblasts was highly sensitive to the dimensions TiNTs, the preadsorbed COL and FN could reduce the difference. Molecular dynamics (MD) simulation results confirmed that the main driving force for protein adsorption was the physical adsorption. The TiNTs with bigger dimensions had higher interaction energies, and thus leading to higher proteins (COL and FN) adsorption and obvious influences on cell behaviors. MD simulation revealed that the orientation and conformation of proteins adsorbed onto surfaces of TiNTs was critical for cell integrins to recognize specific sites. When FN molecules adsorbed onto the surfaces of TiNTs, their RGD (Arg-Gly-Asp) sites were easily exposed to outside and more likely to bond with the fibronectin receptors, in turn regulating the cellular behaviors.

To investigate the influence of magnetized hydroxyapatite on the growth and differentiation of osteoblasts, hydroxyapatite (HA) and magnetized hydroxyapatite (mHA) were synthesized and characterized. The cell viability, differentiation, and morphologies of osteoblasts were investigated in vitro, respectively. The results showed that compared to HA, cells cultured with mHA had better cell viability, and both HA and mHA were beneficial to the early differentiation of osteoblasts. Furthermore, the interaction mechanism between mHA and osteoblasts was elucidated using a molecular dynamics simulation. The simulation results indicated that when cultured with osteoblasts, HA adsorbed bovine serum protein onto its surface from the medium immediately, which was beneficial to the adhesion and proliferation of osteoblasts. The main driving force for the adsorption of bovine serum was the electronic properties of HA crystal faces. The (211) crystal face of HA had the highest electron density among its all crystal faces, thus mainly contributing to the protein adsorption of HA. Nevertheless, the (211) crystal face of mHA still had a relatively higher electron density than that of HA, thus possessing better protein adsorption than that of HA, and in turn promoting the biological functions of osteoblasts.

To enhance corrosion resistance of WE43 magnesium alloy, chitosan (CHI) and poly (styrene sulfonate) (PSS) polyelectrolyte multilayers were fabricated on micro-arc oxidation (MAO) treated magnesium alloy substrate via layer-by-layer (LBL) self-assembly technique. Surface morphology and chemical composition of the MAO/LBL composite coating were investigated by scanning electron microscopy (SEM), atomic force microscope (AFM) and X-ray photoelectron spectroscopy (XPS), respectively. Potentiodynamic polarization test and hydrogen evolution measurement showed that the formed MAO/LBL coating significantly enhanced corrosion resistance of WE43 magnesium alloy in simulated body fluid (SBF). The approach presented here affords an effective alternative for surface modification of magnesium-based materials to meet the requirements of biomaterials applications.

A novel redox responsive controlled drug release system based on magnetic nanoparticles for efficient intracellular anticancer drug delivery is fabricated. Disulfide bonds are employed as intermediate linkers to immobilize PEI/β-CD molecules as nanoreservoirs for drug loading onto magnetic nanoparticles. The endocytotic pathway and endosomal escape of the smart controlled drug release system is proposed.

To improve the corrosion resistance of magnesium alloy, we reported a novel approach for the fabrication of anticorrosive multilayers onto AZ91D substrates. The multilayers were composed of poly(ethylene imine) (PEI), poly(styrene sulfonate) (PSS) and 8-hydroxyquinoline (8HQ). They were deposited onto AZ91D substrates via a spin-assisted layer-by-layer (LbL) technique. The multilayered structure was stabilized with glutaraldehyde (GA) as crossing linker. It was confirmed by Fourier transform infrared spectroscopy (FT-IR). Surface morphologies and elemental compositions of the formed anticorrosive multilayers were characterized with scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), respectively. The corrosion performance of the multilayer coated AZ91D substrates was characterized by hydrogen evolution. The results of electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization measurements suggested that the multilayered coating improved the corrosion resistance of AZ91D substrates. In vitro study revealed that the multilayered coating was cytocompatible. The study provides a potential alternative for the fabrication of corrosion resistant magnesium alloy-based implants.

In this study, the theoretical structures of armchair (6, 6) and zigzag (12, 0) TiO2 nanotubes (TiNTs) were constructed by rolling the (101) layer of an anatase TiO2 crystal. The (101) layer was made using Materials Studio (MS) by cutting the cleave plane (101) of the anatase TiO2 crystal. Based on these structures, the basic properties of TiO2 nanotubes were investigated using MS. Molecular dynamics simulations were performed using the software NAMD to investigate the status and permeation of water through the TiO2 nanotubes. Structure analysis shows that both the inner and outer walls of the structures were terminated with oxygen atoms. The thicknesses of single tube walls are smaller than that of a perfect triple layer (2.20 A) in bulk anatase TiO2. With regard to the bulk Ti–O bond length, the Ti–O bonds in the outer layer are elongated, and are shortened in the inner layer. Molecular dynamics simulation shows that the water molecules in the nanotubes move back and forth, as in one-dimensional Brownia...

To improve the corrosion resistance and biological performance of commercially pure titanium (cp-Ti) substrates, potassium hydroxide was employed to modify the surfaces of titanium substrates, followed by biomimetic deposition of apatite on the substrates in a simulated body fluid. The morphologies of native and treated titanium substrates were characterized by field emission scanning electron microscopy (FE-SEM). Treatment with potassium hydroxide led to the formation of intermediate layers of potassium titanate on the surfaces of titanium substrates, while apatite was subsequently deposited onto the intermediate layer. The formation of potassium titanate and apatite was confirmed by thin-film X-ray diffraction and FE-SEM equipped with energy dispersive spectroscopy, respectively. Electrochemical impedance spectroscopy showed that the formed potassium titanate layer improved the corrosion-resistance properties of titanium substrates. The influence of modified titanium substrates on the biological behavior of mesenchymal stem cells (MSCs), including osteogenic differentiation, was investigated in vitro. Compared with cp-Ti substrates, MSCs cultured onto alkali- and heat-treated titanium substrates and apatite-deposited titanium substrates displayed significantly higher (P0.05 or P0.01) proliferation and differentiation levels of alkaline phosphatase and osteocalcin in 7 and 14day cultures, respectively. More importantly, our results suggest that the modified titanium substrates have great potential for inducing MSCs to differentiate into osteoblasts. The approach presented here may be exploited to fabricate titanium-based implants.

In this study, the mechanical properties and glass transition temperature of PLA-PEG block copolymer were investigated by molecular dynamic simulation. The software package Discover in Materials Studio with condensed-phase optimized molecular potentials for atomistic simulation studies (COMPASS) force field was used for the simulation. To verify the validity of simulation results, PLA and PLA-PEG copolymer were prepared in this research and the glass transition temperature was measured by DSC. The simulation results showed that the random combination chain has more probability than the alternating combination chain to exist in copolymer structure. Furthermore, PLA-PEG block copolymer has better tensile strength but lower shear strength than PLA, which agree well with the theoretical results. The simulation values of Tg (PLA: 333.97 K and PLA-PEG: 326.70 K) agree well with the DSC results (PLA: 328.8 K and PLA-PEG: 321.3 K). The conclusion could be drawn from the results that molecular dynamic simulation (...

A novel composite of α-methyl methacrylate (MMA) grafted sodium alginate (NaAlg) and hydroxyapatite (HA) was prepared in this study. The compositions and chemical groups of materials were investigated by infrared spectra (IR), X-ray diffraction (XRD) and nuclear magnetic resonance (NMR). The results showed that MMA has been successfully grafted with the hydroxyl group of sodium alginate. Moreover many chemical bonds existed in the composite, including the “egg-box” structure and hydrogen bonding. Meanwhile, the chemical bondings between MMA and sodium alginate partly replaced the intermolecular hydrogen bonding or the intramolecular hydrogen bonding in sodium alginate. The composite had better water contact angle than sodium alginate, indicating the strong hydrophilic character of pure sodium alginate was improved. The molecular dynamics (MD) method was used to simulate and evaluate the interaction energies based on the theoretics, which suggested that the copolymer whose every monomer grafted with one MMA had a more stable structure.