Fabrication of a Nanoscale Magnesium/Copper Metal-Organic Framework on Zn-Based Guided Bone Generation Membranes for Enhancing Osteogenesis, Angiogenesis, and Bacteriostasis Properties.

Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal-organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu2+. As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn2+, Mg2+, and Cu2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.

Incorporation of Magnesium and Zinc Metallic Particles in PLGA Bi-layered Membranes with Sequential Ion Release for Guided Bone Regeneration.

Guided bone regeneration (GBR) membranes are commonly used for periodontal tissue regeneration. Due to the complications of existing GBR membranes, the design of bioactive membranes is still relevant. GBR membranes with an asymmetric structure can accommodate the functional requirements of different interfacial tissues. Here, poly(lactic acid-glycolic acid) (PLGA) was selected as the matrix for preparing a bi-layered membrane with both dense and porous structure. The dense layer for blocking soft tissues was incorporated with zinc (Zn) particles, while the porous layer for promoting bone regeneration was co-incorporated with magnesium (Mg) and Zn particles. Mg/Zn-embedded PLGA membranes exhibited 166% higher mechanical strength in comparison with pure PLGA membranes and showed suitable degradation properties with a sequential ion release behavior of Mg2+ first and continuously Zn2+. More importantly, the release of Zn2+ from bi-layered PLGA endowed GBR membranes with excellent antibacterial activity (antibacterial rate > 69.3%) as well as good cytocompatibility with MC3T3-E1 (mouse calvaria pre-osteoblastic cells) and HGF-1 (human gingival fibroblast cells). Thus, the asymmetric bi-layered PLGA membranes embedded with Mg and Zn particles provide a simple and effective strategy to not only reinforce the PLGA membrane but also endow membranes with osteogenic and antibacterial activity due to the continuous ion release profile, which serves as a promising candidate for use in GBR therapy.

Angiogenesis coupled with osteogenesis in a bone tissue engineering scaffold enhances bone repair in osteoporotic bone defects.

Increased life expectancy has resulted in an increase in osteoporosis incidence worldwide. The coupling of angiogenesis and osteogenesis is indispensable for bone repair. Although traditional Chinese medicine (TCM) exerts therapeutic effects on osteoporosis, TCM-related scaffolds, which focus on the coupling of angiogenesis and osteogenesis, have not yet been used for the treatment of osteoporotic bone defects.Panax notoginsengsaponin (PNS), the active ingredient ofPanax notoginseng, was added to a poly (L-lactic acid) (PLLA) matrix. Osteopractic total flavone (OTF), the active ingredient ofRhizoma Drynariae, was encapsulated in nano-hydroxyapatite/collagen (nHAC) and added to the PLLA matrix. Magnesium (Mg) particles were added to the PLLA matrix to overcome the bioinert character of PLLA and neutralize the acidic byproducts generated by PLLA. In this OTF-PNS/nHAC/Mg/PLLA scaffold, PNS was released faster than OTF. The control group had an empty bone tunnel; scaffolds containing OTF:PNS = 100:0, 50:50, and 0:100 were used as the treatment groups. Scaffold groups promoted new vessel and bone formation, increased the osteoid tissue, and suppressed the osteoclast activity around osteoporotic bone defects. Scaffold groups upregulated the expression levels of angiogenic and osteogenic proteins. Among these scaffolds, the OTF-PNS (50:50) scaffold exhibited a better capacity for osteogenesis than the OTF-PNS (100:0 and 0:100) scaffolds. Activation of the bone morphogenic protein (BMP)-2/BMP receptor (BMPR)-1A/runt-related transcription factor (RUNX)-2signaling pathway may be a possible mechanism for the promotion of osteogenesis. Our study demonstrated that the OTF-PNS/nHAC/Mg/PLLA scaffold could promote osteogenesis via the coupling of angiogenesis and osteogenesis in osteoporotic rats with bone defects, and activating theBMP-2/BMPR1A/RUNX2signaling pathway may be an osteogenesis-related mechanism. However, further experiments are necessary to facilitate its practical application in the treatment of osteoporotic bone defects.

Tests and classification methods in adaptive designs with applications.

Statistical tests for biomarker identification and classification methods for patient grouping are two important topics in adaptive designs of clinical trials related to genomic studies. In this article, we evaluate four test methods for biomarker identification in the first stage of an adaptive design: a model-based identification method, the popular two-sided t-test, the nonparametric Wilcoxon Rank-Sum test (two-sided), and the Regularized Generalized Linear Models. For patients grouping in the second stage, we examine classification methods such as Random Forest, Elastic-net Regularized Generalized Linear Models, Support Vector Machine (SVM), Gradient Boosting Machine (GBM), and Extreme Gradient Boosting (XGBoost). Simulation studies are carried out to assess the performance of the different methods. The best identification methods are chosen based on the well-known F 1 score, while the best classification techniques are selected based on the area under a receiver operating characteristic curve (AUC). The chosen methods are then applied to the Adaptive Signature Design (ASD) with a real data set from breast cancer patients for the purpose of evaluating the performance of ASD in different situations.

Sequential Release of Panax Notoginseng Saponins and Osteopractic Total Flavone from Poly (L-Lactic Acid) Scaffold for Treating Glucocorticoid-Associated Osteonecrosis of Femoral Head.

Glucocorticoids inhibit angiogenesis in the femoral head, which fails to nourish the bone tissue and leads to osteonecrosis. Restoring angiogenesis is not only essential for vessel formation, but also crucial for osteogenesis. Poly (L-lactic acid) (PLLA) is commonly used in the bone tissue engineering field. Panax notoginseng saponins (PNS) and osteopractic total flavone (OTF) promote angiogenesis and osteogenesis, respectively. We designed a sequentially releasing PLLA scaffold including PLLA loaded with OTF (inner layer) and PLLA loaded with PNS (outer layer). We assessed the osteogenic effect of angiogenesis in this scaffold by comparing it with the one-layered scaffold (PLLA embedded with OTF and PNS) in vivo. Results from the micro-CT showed that the data of bone mineral density (BMD), bone volume (BV), and percent bone volume (BV/TV) in the PO-PP group were significantly higher than those in the POP group (p < 0.01). Histological analyses show that the PO-PP scaffold exhibits better angiogenic and osteogenic effects compared with the one-layered scaffold. These might result from the different structures between them, where the sequential release of a bi-layer scaffold achieves the osteogenic effect of vascularization by initially releasing PNS in the outer layer. We further explored the possible mechanism by an immunohistochemistry analysis and an immunofluorescence assay. The results showed that the protein expressions of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1(CD31) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.01); the protein expressions of osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.05). Upregulating the expressions of angiogenic and osteogenic proteins might be the possible mechanism.

In-situmineralized homogeneous collagen-based scaffolds for potential guided bone regeneration.

For guided bone regeneration (GBR) in clinical orthopedics, the importance of a suitable scaffold which can provide the space needed for bone regeneration and simultaneously promotes the new bone formation cannot be overemphasized. Due to its excellent biocompatibility, mechanical strength, and similarity in structure and composition to natural bone, the mineralized collagen-based scaffolds have been increasingly considered as promising GBR scaffolds. Herein, we propose a novel method to fabricate anin-situmineralized homogeneous collagen-based scaffold (IMHCS) with excellent osteogenic capability for GBR by electrospinning the collagen solution in combination with essential mineral ions. The IMHCS exhibited homogeneous distribution of apatite crystals in electrospun fibers, which helped to achieve a significantly higher tensile strength than the pure collagen scaffold (CS) and the scaffold with directly added nano-hydroxyapatite particles (HAS). Furthermore, the IMHCS had significantly better cell compatibility, cell migration ratio, and osteogenic differentiation property than the HAS and CS. Therefore, the IMHCS not only retains traditional function of inhibiting fibroblast invasion, but also possesses excellent osteogenic differentiation property, indicating a robust alternative for GBR applications.

Biomechanics and mechanobiology of the bone matrix.

The bone matrix plays an indispensable role in the human body, and its unique biomechanical and mechanobiological properties have received much attention. The bone matrix has unique mechanical anisotropy and exhibits both strong toughness and high strength. These mechanical properties are closely associated with human life activities and correspond to the function of bone in the human body. None of the mechanical properties exhibited by the bone matrix is independent of its composition and structure. Studies on the biomechanics of the bone matrix can provide a reference for the preparation of more applicable bone substitute implants, bone biomimetic materials and scaffolds for bone tissue repair in humans, as well as for biomimetic applications in other fields. In providing mechanical support to the human body, bone is constantly exposed to mechanical stimuli. Through the study of the mechanobiology of the bone matrix, the response mechanism of the bone matrix to its surrounding mechanical environment can be elucidated and used for the health maintenance of bone tissue and defect regeneration. This paper summarizes the biomechanical properties of the bone matrix and their biological significance, discusses the compositional and structural basis by which the bone matrix is capable of exhibiting these mechanical properties, and studies the effects of mechanical stimuli, especially fluid shear stress, on the components of the bone matrix, cells and their interactions. The problems that occur with regard to the biomechanics and mechanobiology of the bone matrix and the corresponding challenges that may need to be faced in the future are also described.

Anti-Inflammatory and Mineralization Effects of an ASP/PLGA-ASP/ACP/PLLA-PLGA Composite Membrane as a Dental Pulp Capping Agent.

Dental pulp is essential for the development and long-term preservation of teeth. Dental trauma and caries often lead to pulp inflammation. Vital pulp therapy using dental pulp-capping materials is an approach to preserving the vitality of injured dental pulp. Most pulp-capping materials used in clinics have good biocompatibility to promote mineralization, but their anti-inflammatory effect is weak. Therefore, the failure rate will increase when dental pulp inflammation is severe. The present study developed an amorphous calcium phosphate/poly (L-lactic acid)-poly (lactic-co-glycolic acid) membrane compounded with aspirin (hereafter known as ASP/PLGA-ASP/ACP/PLLA-PLGA). The composite membrane, used as a pulp-capping material, effectively achieved the rapid release of high concentrations of the anti-inflammatory drug aspirin during the early stages as well as the long-term release of low concentrations of aspirin and calcium/phosphorus ions during the later stages, which could repair inflamed dental pulp and promote mineralization. Meanwhile, the composite membrane promoted the proliferation of inflamed dental pulp stem cells, downregulated the expression of inflammatory markers, upregulated the expression of mineralization-related markers, and induced the formation of stronger reparative dentin in the rat pulpitis model. These findings indicate that this material may be suitable for use as a pulp-capping material in clinical applications.

Physical and Chemical Characterization of Biomineralized Collagen with Different Microstructures.

Mineralized collagen is the basic unit in hierarchically organized natural bone with different structures. Polyacrylic acid (PAA) and periodic fluid shear stress (FSS) are the most common chemical and physical means to induce intrafibrillar mineralization. In the present study, non-mineralized collagen, extrafibrillar mineralized (EM) collagen, intrafibrillar mineralized (IM) collagen, and hierarchical intrafibrillar mineralized (HIM) collagen induced by PAA and FSS were prepared, respectively. The physical and chemical properties of these mineralized collagens with different microstructures were systematically investigated afterwards. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed that mineralized collagen with different microstructures was prepared successfully. The pore density of the mineralized collagen scaffold is higher under the action of periodic FSS. Fourier transform infrared spectroscopy (FTIR) analysis showed the formation of the hydroxyapatite (HA) crystal. A significant improvement in the pore density, hydrophilicity, enzymatic stability, and thermal stability of the mineralized collagen indicated that the IM collagen under the action of periodic FSS was beneficial for maintaining collagen activity. HIM collagen fibers, which are prepared under the co-action of periodic FSS and sodium tripolyphosphate (TPP), may pave the way for new bone substitute material applications.

Synergistically Detachable Microneedle Dressing for Programmed Treatment of Chronic Wounds.

Chronic wounds such as diabetic feet undergo a lifetime risk of developing into incurable ulcers. Current treatments for chronic wounds remain unsatisfactory due to the lack of ideal wound dressings that integrate facile dressing change, long-acting treatment, and high therapeutic efficacy into one system. Herein, a synergistically detachable microneedle (MN) dressing with a dual-layer structure is presented to enable programmed treatment via one-time dressing application. Such a dual-layer dressing MN system (DDMNS) is composed of chitosan (CS) hydrogel dressing (CSHD) on top of a detachable MN patch with a CS tip and a polyvinyl pyrrolidone (PVP) backing substrate incorporated with magnesium (Mg). The synergistic detachment is achieved with the backing Mg/PVP substrate dissolving within minutes due to the local moist environment of the CSHD enhancing the reaction between Mg and inflammation microenvironment. The combined treatment of Mg and panax notoginseng saponins (PNS) loaded in DDMNS achieves antibacterial, neovascularization, and activating a benign immune response so that the three overlapping periods of the inflammation, tissue proliferation, and tissue remodeling of wound healing reach a dynamic balance. This advanced DDMNS provides a facile approach for the programmed treatment of chronic wound management indicating potential value in wound healing and other related biomedical fields.

Orthophosphate and alkaline phosphatase induced the formation of apatite with different multilayered structures and mineralization balance.

Mineralized collagen is a natural organic-inorganic composite. The combination of organic collagen and inorganic apatite to form different nanostructures is the key to producing bone substitutes with biomechanical properties that are as identical to normal bone as possible. However, the formation of apatite with different nanostructures during collagen mineralization is unexplored. Here, pyrophosphate (Pyro-P), as an important hydrolysate of adenosine triphosphate in the body, was introduced to prepare mineralized collagen under the regulation of alkaline phosphatase (ALP) and orthophosphate (Ortho-P). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results showed that mineralized collagen, which combined with different crystallinities and multilayered structured apatite, was successfully prepared. A combination of ion chromatography (IC), Fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD), and thermogravimetry (TG) analyses revealed the crucial role of Ortho-P in the formation of multilayered flower-shaped apatite with different crystallinities and in the maintenance of mineralization balance. Mineralization balance is of great significance for maintaining normal bone morphology during bone regeneration. Overall, our results provide a promising method to produce new bone substitute materials for the repair of large bone defects and a deeper insight into the mechanisms of biomineralization.

The pro-inflammatory response of macrophages regulated by acid degradation products of poly(lactide-co-glycolide) nanoparticles.

Poly(lactide-co-glycolide) (PLGA) shows great potentials in biomedical applications, in particular with the field of biodegradable implants and control release technologies. However, there are few systematic and detailed studies on the influence of PLGA degradation behavior on the immunogenicity. In this study, in order to develop a method for dynamically assessing the immunological response of PLGA throughout the implantation process, PLGA particles are fabricated using an o/w single-emulsion method. The physicochemical characterizations of the prepared PLGA particles during in vitro hydrolytic degradation are investigated. Then, a series of immunological effects triggered by PLGA by-products formed with degradation process are evaluated, including cell viability, apoptosis, polarization and inflammatory reaction. THP-1 human cell line is set as in vitro cell model. Our results show that PLGA degradation-induced acid environment decreases cell viability and increases cell apoptosis, which is a potential factor affecting cell function. In particular, the macrophages exhibit up-regulations in both M1 subtype related surface markers and pro-inflammatory cytokines with the degradation process of PLGA, which indicates the degradation products of PLGA can convert macrophages to the pro-inflammatory (M1) polarization state. All these findings provide the mechanism of PLGA-induced inflammation and lay the foundation for the design of next-generation PLGA-based biomaterials endowed with immunomodulatory functions.

Three-dimensional silk fibroin scaffolds incorporated with graphene for bone regeneration.

Porous three-dimensional (3D) silk fibroin (SF) scaffolds were widely applied for bone regeneration and showed excellent biocompatibility and biodegradability. Recently graphene was developed for bone scaffolds due to its osteogenic properties. Thus, we combine the SF and graphene to improve the osteogenic properties of SF scaffolds. In our study, we explored the incorporation of SF scaffolds with graphene to develop osteogenic scaffolds capable of accelerating bone formation. The 3D SF scaffolds were fabricated with different contents of graphene (0, 0.5, and 2%). Fluorescence images showed that the graphene nanosheets were homogeneously dispersed in the SF scaffolds. The addition of graphene affected the microarchitecture of the scaffolds. The G/SF scaffolds were cocultured with rat bone marrow-derived mesenchymal stem cells (rBMSCs) for 21 days. The cell morphology and cell proliferation study suggested that 0 and 0.5% G/SF scaffolds displayed good cell proliferation. In addition, immunofluorescent staining (e.g., osteonectin, osteopontin, and osteocalcin) and ALP activities indicated that the osteogenic properties was more actively exhibited on 0.5% G/SF scaffolds compared with the other groups. Our results indicated that SF scaffolds incorporated with graphene could be an appropriate scaffold for bone tissue engineering.

Bioinspired mineralized collagen scaffolds for bone tissue engineering.

Successful regeneration of large segmental bone defects remains a major challenge in clinical orthopedics, thus it is of important significance to fabricate a suitable alternative material to stimulate bone regeneration. Due to their excellent biocompatibility, sufficient mechanical strength, and similar structure and composition of natural bone, the mineralized collagen scaffolds (MCSs) have been increasingly used as bone substitutes via tissue engineering approaches. Herein, we thoroughly summarize the state of the art of MCSs as tissue-engineered scaffolds for acceleration of bone repair, including their fabrication methods, critical factors for osteogenesis regulation, current opportunities and challenges in the future. First, the current fabrication methods for MCSs, mainly including direct mineral composite, in-situ mineralization and 3D printing techniques, have been proposed to improve their biomimetic physical structures in this review. Meanwhile, three aspects of physical (mechanics and morphology), biological (cells and growth factors) and chemical (composition and cross-linking) cues are described as the critical factors for regulating the osteogenic feature of MCSs. Finally, the opportunities and challenges associated with MCSs as bone tissue-engineered scaffolds are also discussed to point out the future directions for building the next generation of MCSs that should be endowed with satisfactorily mimetic structures and appropriately biological characters for bone regeneration.

Electrochemically Enabled Embedded Three-Dimensional Printing of Freestanding Gallium Wire-like Structures.

The ability to pattern planar and freestanding 3D metallic architectures would enable numerous applications, including flexible electronics, displays, sensors, and antennas. Low melting point metals, such as gallium, have recently drawn considerable attention especially in the fields of flexible and stretchable electronics and devices owing to its unique properties, such as excellent electrical conductivity and fluidity. However, the large surface tension, low viscosity, and large density pose great challenges to 3D printing of freestanding gallium structures in a large scale, which hinder its further applications. In this article, we first propose an electrochemically enabled embedded 3D printing (3e-3DP) method for creating planar and freestanding gallium wire-like structures assisted with supporting hydrogel. After an enhanced solidification process and the removal of hydrogel, various freestanding 2D and 3D wire-like structures are realized. By simply reassembling the gallium structure into soft elastomer, a gallium-based flexible conductor and a 3D-spiral pressure sensor are demonstrated. Above all, this study presents a brand-new and economical way for the fabrication of 2D and 3D freestanding gallium structures, which has great prospects in wide applications in flexible and stretchable electronics and devices.

In vitro immunomodulation of magnesium on monocytic cell toward anti-inflammatory macrophages.

Biodegradable magnesium (Mg) has shown great potential advantages over current bone fixation devices and vascular scaffold technologies; however, there are few reports on the immunomodulation of corrosive Mg products, the micron-sized Mg particles (MgMPs). Human monocytic leukemia cell line THP-1 was set as the in vitro cell model to estimate the immunomodulation of MgMPs on cell proliferation, apoptosis, polarization and inflammatory reaction. Our results indicated high-concentration of Mg2+ demoted the proliferation of the THP-1 cells and, especially, THP-1-derived macrophages, which was a potential factor that could affect cell function, but meanwhile, cell apoptosis was almost not affected by Mg2+. In particular, the inflammation regulatory effects of MgMPs were investigated. Macrophages exposed to Mg2+ exhibited down-regulated expressions of M1 subtype markers and secretions of pro-inflammatory cytokines, up-regulated expression of M2 subtype marker and secretion of anti-inflammatory cytokine. These results indicated Mg2+ could convert macrophages from M0 to M2 phenotype, and the bioeffects of MgMPs on human inflammatory cells were most likely due to the Mg2+-induced NF-κB activation reduction. Together, our results proved Mg2+ could be used as a new anti-inflammatory agent to suppress inflammation in clinical applications, which may provide new ideas for studying the immunomodulation of Mg-based implants on human immune system.

Raloxifene improves TNF-α-induced osteogenic differentiation inhibition of bone marrow mesenchymal stem cells and alleviates osteoporosis.

Effect of raloxifene (RLF) on the improvement of inhibited osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) resulted from tumor necrosis factor-α (TNF-α) induction, thus alleviating the progression of osteoporosis (OP), was investigated. An in vivo OP rat model was constructed by performing the procedures of ovariectomy (OVX). Rats were randomly divided into sham group, OVX group and RLF+OVX group. BMSCs were extracted from healthy rats, and randomly divided into control group, TNF-α group, RLF group and TNF-α+RLF group. Viability and cellular calcification ability in each group were detected. The relative levels of osteocalcin (OCN), Runx2 and NF-κB in cells with different treatments were determined. The body weight of rats in the OVX group and RLF+OVX group gradually increased compared with that in the sham group on the 8th week. No significant difference in body weight was observed between the rats of the OVX group and RLF+OVX group. Bone metabolism index (BMD) in the rats of the RLF+OVX group was higher than that of the OVX group, and lower compared with that of the sham group. Compared with the sham group, the elastic/max radial degree and elastic/max load of femora were reduced in the OVX group and RLF+OVX group, especially in the OVX group. The relative levels of OCN and Runx2, as well as the ALP activity and calcification ability, were decreased in the OVX group compared with the sham group, and the effect was partially reversed by the RLF treatment. After osteogenic differentiation of BMSCs, the viability and calcification ability were markedly reduced in TNF-α group, which was reversed by RLF treatment. Moreover, TNF-α induction downregulated the relative levels of OCN and Runx2, and RLF treatment could enhance their levels. The upregulated NF-κB protein level, induced by TNF-α, was reduced after RLF treatment. TNF-α induction inhibits osteogenic differentiation of BMSCs, which could be remarkably alleviated by RLF. It is suggested that RLF contributes to the alleviation of OP progression.

Fabrication and antibacterial properties of cefuroxime-loaded TiO2 nanotubes.

The anodized titanium nanotubes (TiO2-NTs) are considered to be a potential material in clinical therapy. To enhance the antibacterial property of TiO2-NTs, cefuroxime is introduced into TiO2-NTs, and then, different chitosan layers are coated to control the release of cefuroxime. SEM and FTIR are adapted for the characterization of prepared TiO2-NTs. The effects of chitosan coating thickness on release of cefuroxime are also investigated, followed with the antibacterial property evaluation. The results show TiO2-NTs are fabricated by anodization method and cefuroxime is also successfully loaded into the nanotubes. The thickness of chitosan coating is an important factor to the release rate of cefuroxime. Antimicrobial detection and morphology observation of S. aureus show a sustained 7-day drug release and strong negative effect on bacteria. The approach in this study provides a broadly applicable method to fabricate titanium-based orthopedic implants with enhanced antibacterial properties.

Highly aligned hierarchical intrafibrillar mineralization of collagen induced by periodic fluid shear stress.

Periodic fluid shear stress (FSS) is one of the main mechanical microenvironments in mineralization of bone matrix. To elucidate the mechanism of periodic FSS in collagen mineralization, a mechanical loading induced mineralization system is developed and compared with traditional polyacrylic acid (PAA) induced mineralization. Fourier transform infrared (FTIR) spectroscopy, calcium-to-phosphorus molar ratio and transmission electron microscopy (TEM) demonstrate that both periodic FSS and PAA can control the size of amorphous calcium phosphate (ACP) to avoid aggregation and help the formation of intrafibrillar mineralization. Differently, periodic FSS under a proper cycle and range can accelerate the conversion of ACP to apatite crystals and alleviate the reduced transformation caused by PAA. Under the action of template analogues, periodic FSS can also promote the formation of highly oriented hierarchical intrafibrillar mineralized (HIM) collagen. These findings are helpful for understanding the mechanism of collagen mineralization in natural bone matrix and contribute to the design of novel bone substitute materials with hierarchical structures.

Terminal Group Modification of Carbon Nanotubes Determines Covalently Bound Osteogenic Peptide Performance.

Osteogenic peptides are often introduced to improve biological activities and the osteogenic ability of artificial bone materials as an effective approach. Covalent bindings between the peptide and the host material can increase the molecular interactions and make the functionalized surface more stable. However, covalent bindings through different functional groups can bring different effects on the overall bioactivities. In this study, carboxyl and amino groups were respectively introduced onto carbon nanotubes, a nanoreinforcement for synthetic scaffold materials, which were subsequently covalently attached to the RGD/BMP-2 osteogenic peptide. MC3T3-E1 cells were cultured on scaffolds containing peptide-modified carbon nanotubes. The results showed that the peptide through the amino group binding could promote cell functions more effectively than those through carboxyl groups. The mechanism may be that the amino group could bring more positive charges to carbon nanotube surfaces, which further led to differences in the peptide conformation, protein adsorption, and targeting osteogenic effects. Our results provided an effective way of improving the bioactivities of artificial bone materials by chemically binding osteogenic peptides.