Material surface is a key determinant of host response on implanted biomaterial. Therefore, modification of the implant surface may optimize implant-tissue reactions. Inflammatory reaction is inevitable after biomaterial implantation, but prolonged inflammation may lead to adverse reactions and subsequent implant failure. Proinflammatory activities of cytokines like interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are attractive indicators of these processes and ultimately characterize biocompatibility. The objective of the study was to evaluate local cytokine production after implantation of stainless steel 316L (SS) and titanium alloy (Ti6Al4V) biomaterials coated with titanium dioxide (TiO2) and silica (SiO2) coatings prepared by sol-gel method. Biomaterials were implanted into rat femur and after 12 weeks, bones were harvested. Bone-implant tissue interface was evaluated; immunohistochemical staining was performed to identify IL-6, TNF-α, and Caspase-1. Histomorphometry (AxioVision Rel. 4.6.3 software) of tissue samples was performed in order to quantify the cytokine levels. Both the oxide coatings on SS and Ti6Al4V significantly reduced cytokine production. However, the lowest cytokine levels were observed in TiO2 groups. Cytokine content in uncoated groups was lower in Ti6Al4V than in SS, although coating of either metal reduced cytokine production to similar levels. Sol-gel TiO2 or SiO2 coatings reduced significantly the production of proinflammatory cytokines by local tissues, irrespective of the material used as a substrate, that is, either Ti6Al4V or SS. This suggests lower inflammatory response, which directly points out improvement of materials' biocompatibility.

Micro-sized sponge particulates have attracted extensive attention because of their potential to overcome the intrinsic limitations of conventional monolithic scaffolds in tissue engineering. Bioactive nanocomposite microsponges are regarded as potential bone substitute materials for bone regeneration.

The conventional techniques for the preparation of reconstituted high-density lipoprotein (rHDL) are hampered by long process times, the need for large amounts of starting material, and harsh preparation conditions. Here, we present a novel rHDL preparation method to overcome these challenges. Furthermore, we propose a dual mode of action for rHDL loaded with the immunosuppressant drug everolimus (Eve-rHDL) in the context of atherosclerosis and cardiovascular disease.

The purpose of the present study was to use capacitive coupling of pulsed electromagnetic field (CC-PEMF) and hydroxyapatite nanoparticles (HAp) as a countermeasure to prevent osteoporosis induced by simulated microgravity. We used the hind-limb suspension (HLS) rat model to simulate microgravity-induced bone losses for 45 days. In order to compare the resulting changes, mineralogical (bone mineral density [BMD], calcium [Ca], and phosphorus [P]), biochemical (osteocalcin, alkaline phosphatase [ALP], and type I collagen), and histological (scanning electron microscopy) parameters were adopted. As a countermeasure to the above, the effect of PEMF and HAp application were examined. Three-month-old female Wistar rats were randomly divided into control (n = 8), HLS (n = 8), HLS with PEMF (n = 8), HLS with HAp nanoparticles (n = 8), and HLS with HAp and PEMF (n = 8). We observed: 1) significant decrease (p < 0.01) in BMD, Ca, P, type I collagen, and ALP activity in femur and tibia in hind-limb bone and serum osteocalcin in HLS rats as compared with the ground control. 2) Nonsignificant increase in BMD (p < 0.1), Ca (p < 0.1), P (p < 0.5), type I collagen (p < 0.1), and ALP activity (p < 0.5) in femur and tibia in hind-limb bone and serum osteocalcin (p < 0.5) in HLS + PEMF rats compared with HLS rats. 3) Significant increase in BMD (p < 0.02), Ca (p < 0.05), P (p < 0.05), type I collagen (p < 0.02), and ALP activity (p > 0.02) in femur and tibia in hind-limb bone with a nonsignificant increase in serum osteocalcin (p > 0.1) in HLS + HAp rats compared to HLS rats. 4) Significant increase in BMD (p > 0.01). Ca (p > 0.01). P (p > 0.01). type I collagen (p > 0.01). and ALP activity (p > 0.01) in femur and tibia in hind-limb bone and serum osteocalcin (p > 0.02) were also observed. Results suggest that a combination of low level PEMF and Hap nanoparticles has potential to control bone loss induced by simulated microgravity.

Three of the main requirements that remain major challenges in tissue engineering of the knee meniscus are to engineer scaffolds with compatible anatomical shape, good mechanical properties, and microstructure able to mimic the architecture of the extracellular matrix (ECM). In this context, we presented a new biofabrication strategy to develop a three-dimensional (3D) meniscus-regenerative scaffold with custom-made macroscopic size and microarchitecture bioinspired by the organization of structural fibers of native tissue ECM.

In the present study, the fabrication of novel p(N-isopropylacrylamide-co-butyl methylacrylate) (PIB) nanogels was combined with boron-containing mesoporous bioactive glass (B-MBG) scaffolds in order to improve the mechanical properties of PIB nanogels alone. Scaffolds were tested for mechanical strength and the ability to promote new bone formation in vivo.

The purpose of this study was to develop calcium phosphate nanocomposite particles encapsulating plasmid DNA (CP-pDNA) nanoparticles as a nonviral vector for gene delivery.

Micro-arc oxidation (MAO) is a fast and effective method to prepare nanoporous coatings with high biological activity and bonding strength. Simple micro/nano-coatings cannot fully meet the requirements of osteogenesis. To further improve the biological activity of a titanium surface, we successfully added biological magnesium (Mg2+) to a coating by micro-arc oxidation and evaluated the optimal magnesium concentration in the electrolyte, biocompatibility, cell adhesion, proliferation, and osteogenesis in vitro.

The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. Mesenchymal stem cells (MSCs)-derived exosomes have the same therapeutic effect to MSCs-based therapies. The effect of human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect.

Biomaterials with high osteogenic activity are desirable for sufficient healing of bone defects resulting from trauma, tumor, infection, and congenital abnormalities. Synthetic materials mimicking the structure and composition of human trabecular bone are of considerable potential in bone augmentation. In the present study, a zinc (Zn)-doped mesoporous hydroxyapatite microspheres (Zn-MHMs)/collagen scaffold (Zn-MHMs/Coll) was developed through a lyophilization fabrication process and designed to mimic the trabecular bone. The Zn-MHMs were synthesized through a microwave-hydrothermal method by using creatine phosphate as an organic phosphorus source. Zn-MHMs that consist of hydroxyapatite nanosheets showed relatively uniform spherical morphology, mesoporous hollow structure, high specific surface area, and homogeneous Zn distribution. They were additionally investigated as a drug nanocarrier, which was efficient in drug delivery and presented a pH-responsive drug release behavior. Furthermore, they were incorporated into the collagen matrix to construct a biomimetic scaffold optimized for bone tissue regeneration. The Zn-MHMs/Coll scaffolds showed an interconnected pore structure in the range of 100-300 μm and a sustained release of Zn ions. More importantly, the Zn-MHMs/Coll scaffolds could enhance the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that the Zn-MHMs/Coll scaffolds could enhance bone regeneration compared with the Coll or MHMs/Coll scaffolds. The results suggest that the biomimetic Zn-MHMs/Coll scaffolds may be of enormous potential in bone repair and regeneration.

Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation - the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8+ T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8+ T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8+ T-cells. To achieve this, we have used 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8+ T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials.

The goal for current orthopedic implant research is to design implants that have not only good biocompatibility but also antibacterial properties. TiO2 nanotubes (NTs) were fabricated on the titanium surface through electrochemical anodization, which added new properties, such as enhanced biocompatibility and potential utility as drug nanoreservoirs. The aim of the present study was to investigate the antibacterial properties and biocompatibility of NTs loaded with vancomycin (NT-V), both in vitro and in vivo. Staphylococcus aureus was used to study the antibacterial properties of the NT-V. There were three study groups: the commercially pure titanium (Cp-Ti) group, the NT group (nonloaded vancomycin), and the NT-V group. We compared NT-V biocompatibility and antibacterial efficacy with those of the NT and Cp-Ti groups. Compared with Cp-Ti, NT-V showed good antibacterial effect both in vitro and in vivo. Although the NTs reduced the surface bacterial adhesion in vitro, implant infection still developed in in vivo studies. Furthermore, the results also revealed that both NTs and NT-V showed good biocompatibility. Therefore, the NTs loaded with antibiotic might be potentially used for future orthopedic implants.

The purpose of this study was to investigate the influences of nanoscale wear particles derived from titanium/titanium alloy-based implants on integration of bone. Here we report the potential impact of titanium oxide (TiO2) nanoparticles on adhesion, migration, proliferation, and differentiation of mesenchymal stem cells (MSC) from the cellular level to the molecular level in the Wistar rat.

To investigate the effect of magnetic nanoparticles (MNPs) of Fe(3)O(4) combined with cyclosporin A (CsA) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in murine models.

Innovative nerve conduits for peripheral nerve reconstruction are needed in order to specifically support peripheral nerve regeneration (PNR) whenever nerve autotransplantation is not an option. Specific support of PNR could be achieved by neurotrophic factor delivery within the nerve conduits via nanotechnology or stem cell engineering and transplantation.

Background: Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO2 nanocomposite on bone regeneration and the underlying biological mechanisms. Methods: We oxidized Se2- to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO2 nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO2 nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO2 nanocomposite. The morphology of porous Se@SiO2 nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO2 nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO2 nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO2 nanocomposite. Results: In vitro, intervention with porous Se@SiO2 nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H2O2-induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO2 nanocomposite accelerated bone fracture healing using a rat femur fracture model. Conclusion: Porous Se@SiO2 nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO2 nanocomposite may provide clinic benefit for bone tissue engineering.

The modulus of carbon fiber-reinforced polyether ether ketone (CFR-PEEK), a composite containing layers of carbon fiber sheets, can be precisely controlled to match bone. However, CFR-PEEK is biologically inert and cannot promote bone apposition. The objective of this study was to investigate whether graphene modification could enhance the bioactivity of CFR-PEEK.

In this study, a novel oxygenated nanocomposite thin film, TaON-Ag, was investigated in vitro and in vivo to evaluate its biocompatibility and antibacterial ability.

Ineffective integration has been recognized as one of the major causes of early orthopedic failure of titanium-based implants. One strategy to address this problem is to develop modified titanium surfaces that promote osteoblast differentiation. This study explored titanium surfaces modified with TiO2 nanotubes (TiO2 NTs) capable of localized drug delivery into bone and enhanced osteoblast cell differentiation.

While there have been numerous studies to determine osteoblast (bone forming cell) functions on nanocrystalline compared to micron crystalline ceramics, there have been few studies which have examined osteoclast activity (including tartrate-resistant acid phosphatase, formation of resorption pits, size of resorption pits, and receptor activator of nuclear factor κB [RANK]). This is despite the fact that osteoclasts are an important part of maintaining healthy bone since they resorb bone during the bone remodeling process. Moreover, while it is now well documented that bone formation is enhanced on nanoceramics compared to micron ceramics, some have pondered whether osteoblast functions (such as osteoprotegerin and RANK ligand [RANKL]) are normal (ie, non-diseased) on such materials compared to natural bone. For these reasons, the objective of the present in vitro study was to determine various functions of osteoclasts and osteoblasts on nanocrystalline and micron crystalline hydroxyapatite as well as tri-calcium phosphate materials and compare such results to cortical and cancellous bone. Results showed for the first time similar osteoclast activity (including tartrate-resistant acid phosphatase, formation of resorption pits, size of resorption pits, and RANK) and osteoblast activity (osteoprotegerin and RANKL) on nanocrystalline hydroxyapatite compared to natural bone, whereas osteoclast and osteoblast functions on micron crystalline versions of these ceramics were much different than natural bone. In this manner, this study provides additional evidence that nanocrystalline calcium phosphates can serve as suitable synthetic analogs to natural bone to improve numerous orthopedic applications. It also provides the first data of healthy osteoclast and osteoblast functions on nanocrystalline calcium phosphates compared to natural bone.