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Tissue engineering method provides a promising solution for meniscus repair and regeneration. However, the inflammatory environment that persists after meniscus injury in the knee joint impedes meniscus tissue regeneration. The purpose of this study was to investigate the applicability of silk/graphene oxide (GO)-based meniscus scaffold modified with tannic acid (TA)/Sr2+ coating for the elimination of inflammatory cytokines and reactive oxygen species (ROS) under osteoarthritis (OA) environment along with cartilage protection by using a rat model. The self-assembled coating composed of a series of TA-Sr2+ complex concentrations was formed by a facile, rapid, and efficient method on the scaffold. The phenolic hydroxyl groups on the coating endowed the meniscus scaffold with excellent anti-inflammatory and ROS scavenging capacities. We also found that the coating could promote cell migration in a mock wound model and could increase extracellular matrix secretion in vitro. Moreover, the coating components at a certain concentration played an effective role in delaying OA and providing cartilage protection in the rat model. The expression of inflammation cytokines (e.g., IL-6, IL-8, and MMPs) in rat knee tissue was significantly downregulated, and cartilage degeneration and OA damage were also inhibited according to tissue staining results and the OARSI (Osteoarthritis Research Society International) scoring system. Combining these performances, we suggest that this silk/GO-based scaffold modified with TA/Sr2+ coating could have broader application prospects by virtue of its effective and user-friendly properties. STATEMENT OF SIGNIFICANCE: The biological properties of the meniscus play a role in activating and regulating the metabolic and inflammatory responses that influence the homeostasis of joint health and ultimately lead to knee osteoarthritis (OA). The inflammation condition of the knee joint may exacerbate the degeneration of meniscus and cartilage. The present study aimed to develop a functional coating composed of tannic acid/Sr2+ complex on a silk/graphene oxide-based meniscus scaffold and to endow the scaffold with anti-inflammatory and ROS elimination capacities during the meniscus regeneration process to protect cartilage and delay OA development. The in vitro cytocompatibility study and the in vivo rat OA model study revealed that the coating was effective in promoting cell migration, facilitating ECM secretion, inhibiting inflammation, and delaying OA development.

A well designed coating for polyetheretherketone (PEEK) implants can provide enough support to overcome crucial medical challenges, which are insufficient osseointegration and high rate of infection. Herein, we utilize the co-deposition of polydopamine (PDA) and copper-citrate nanoclusters to construct a pH-responsive coating on porous PEEK for synergistic bone regeneration, vascular formation and anti-infection. Specifically, this PDA coating released high dose of copper and citrate at lower pH value, which increased intracellular copper content, boosted production of reactive oxygen species and severe damage of protein, leading to killing of 93 % planktonic bacterial and eradication of adherent bacteria. At pH of 7.4, the release of copper and citrate were in a slow and sustained behavior, synergistically enhanced vascular formation potential and osteodiffereration of Ad-MSC in vitro. After implanted in rabbit tibia for 6 and 12 weeks, the micro-CT evaluation and histological analysis consistently highlighted the ability of this PDA coating to increase new bone formation adjacent to coated PEEK implant and enhance bone-implant interfacial integration. These results were proven to be related to the synergistic effect that citrate facilitated a 2-fold influx of copper into cells, which not only enhanced the bacteria-killing ability but also encouraged bone regeneration of implants. This present work provides an effective method to control infections while promoting osseointegration simultaneously, which will show tremendous clinical application and can be a solution to current challenges facing orthopedics.

To overcome the restricted degradation, poor antiacterial and osteoindctive problems of magnesium and its alloys, this study presented the spinning coating of an antimicrobial peptide (AP)-loaded silk fibroin (SF) composite onto a corrosion-resistant MgO-coated AZ31 Mg alloy via anodization (aMgO) and electrodeposition (eMgO) methods. The composite coatings not only created a smooth and hydrophilic surface, but also obviously improved the corrosion resistance according to the test of corrosion potential and current density. The colonization of E. coli on MgO-AP composite coatings was significantly reduced as compared to the MgO layers, due to the potential synergetic effects of APs and Mg2+. Compared with the bare AZ31, the composite coating inhibited the corrosion of the substrate and the release of Mg2+, supported the adhesion, spreading and proliferation of osteoblasts, and presented a significantly improved osteogenic differentiation trend. Therefore, the MgO-AP composite coating, which had both antibacterial and bone-promoting abilities, was expected to be applied for surface modification of magnesium alloy implants to solve the clinical problems of bacterial infection and poor osseointegration.

Biomedical device-associated infections (BAI) and osteosynthesis are two main complications following the orthopedic implant surgery, especially while infecting bacteria form a mature biofilm, which can protect the organisms from the host immune system and antibiotic therapy. Comparing with the single antibiotics therapeutic method, the combination of silver nanoparticles (AgNPs) and conventional antibiotics exert a high level of antibacterial activity. Nevertheless, one major issue that extremely restricts the potential application of AgNP/antiviotics is the uncontrolled release. Moreover, the lack of osteogenic ability may cause the osteosynthesis. Thus, herein we fabricated a structure-controlled drug-loaded silk fibroin (SF) coating that can achieve the size and release control of AgNPs and high efficient osteogenesis. Three comparative SF-based coatings were fabricated: α-structured coating (α-helices 32.7%,), m-structured coating (β-sheets 28.3%) and β-structured coating (β-sheets 41%). Owning to the high content of α-helices structure and small AgNPs (20 nm), α-structured coating displayed better protein adsorption and hydrophilicity, as well as pH-dependent and long-lasting antibacterial performance. In vitro studies demonstrated that α coating showed biocompatibility (cellular attachment, spreading and proliferation), high ALP expression, collagen secretion and calcium mineralization. Moreover, after one month subcutaneous implantation in vivo, α-structured coating elicited minimal, comparable inflammatory response. Additionally, in a rabbit femoral defect model, α-structured coating displayed a significant improvement on the generation of new-born bone and bonding between the new bone and the tissue, implying a rapid and durable osteointegration. Expectedly, this optimized structure-controlled SF-based coating can be an alternative and prospective solution for the current challenges in orthopedics. Statement of Significance In this study, an AgNPs/Gentamycin-loaded structured-controlled silk fibroin coatings were constructed on Ti implant's surface to guarantee the success of implantation even in the face of bacterial infection. In comparison, the α-structured coating had the lowest content of β-sheets structure (19.0%) and the smallest particle size of AgNPs (~ 20 nm), and owned pH-responsive characteristic due to reversible α-helices structural. Thanks to pH-responsive release of Ag+, the α-structure coating could effectively inhibit adhesive bacteria and kill planktonic bacteria by releasing a large amount of reactive oxygen radicals. Through in vitro biological results (cell proliferation, differentiation and osteogenic gene expression) and in vivo rabbit femur implantation results, the α-structure coating had good biocompatible and osteogenic properties.

Considering the intrinsic poor self-healing capacity of meniscus, tissue engineering has become a new direction for the treatment of meniscus lesions. However, disturbed by mechanical stability and biocompatibility, most meniscus implants fail to relieve symptoms and prevent the development of osteoarthritis. The goal of this study was to develop a potential meniscal substitute for clinical application. Here, silk fibroin with good mechanical performance and biocompatibility, and strontium ion acting as bioactive factor, were incorporated with Ɛ-Polycaprolactone to fabricate a meniscus scaffold (SP-Sr). By the wet-electrospun method, the 3D SP-Sr provided suitable pore size (100–200 μm) and enough mechanical support (61.6 ± 2.9 MPa for tensile modulus and 0.11 ± 0.03 MPa for compressive modulus). Moreover, after addition of Sr2+, the SP-Sr seeded by rabbit adipose tissue-derived stromal cells (rADSCs) showed the highest secretion with 2.61- and 2.98-fold increase in collagen and aggrecan, respectively, compared with SF/PCL group. And the extracellular matrix related genes expression in SP-Sr also showed upregulation results. Particularly, the expression of the collagen II gene, which played a crucial role in the formation of meniscal inner avascular region, showed a 9-fold increase in SP-Sr compared with pure PCL group. Furthermore, the MRI results of SP-Sr implanted in rabbits with total meniscectomy for 6 months demonstrated effective prevention of meniscus extrusion and relieving joint space narrowing compared with meniscectomy group. And the effects of cartilage protection and delaying osteoarthritis development were confirmed by Pathological examination. Especially, after 6-month implantation, the neo-menisci showed similar structural constituent and mechanical performance. Statement of significance Meniscus regeneration faces great challenge due to the meniscus having limited healing potential owing to its anisotropic structure, its hypocellularity and hypovascularity. The present tissue engineering solutions have failed to maintain the biological function for meniscus reconstruction in vivo because of fragile and poor biocompatible materials, leading to long-term joint degeneration. The goal of this study was to develop a meniscal substitute potential for clinical application. Here, silk fibroin and strontium were incorporated with Ɛ-Polycaprolactone by wet-electrospinning method to fabricate a meniscus scaffold (SP-Sr). The 6-month implantation results revealed that SP-Sr scaffold was effective in preventing meniscus extrusion, cartilage protection and delaying osteoarthritis development, and the regenerated menisci showed similar structural constituent and mechanical performance.

Self-healing coatings have attracted attention on surface modification of magnesium alloys, as it can recover the barrier ability of the coatings from corrosion attack. Nevertheless, previous works on this aspect are not suitable for biomedical magnesium alloys owing to the lack of biocompatibility. In this study, we fabricated a self-healing coating on biomedical Mg-1Ca alloy by compositing silk fibroin and K3PO4. PO43- ions act as corrosion inhibitor, while K3+ ions help to regulate the secondary structures of silk fibroin. The scratch test, scanning vibrating electrode technique (SVET), and electrochemical impedance spectroscopy (EIS) provide comprehensive results, confirming the pH-sensitive self-healing capacity of the composite coating. Moreover, cells' (MC3T3-E1) multiple responses including spreading, adhesion, proliferation, and differentiation illustrate the preferable biocompatibility as well as the osteogenic activity of the coating. These primary findings might open new opportunities in the exploration of self-healing coatings on biomedical magnesium alloys. STATEMENT OF SIGNIFICANCE: Biomedical magnesium alloys surface modifications have been studied for years, which however the biomedical self-healing coatings were rarely involved. In this work, silk fibroin and phosphate (K3PO4) were composited to fabricate coating on biomedical magnesium alloys. The coating not only owned the self-healing ability with pH sensitivity, but also endowed the substrate preferable corrosion resistance as well as osteogenic activity. This work gives a new insight into surface modification for biomedical Mg alloys.

Various coatings have been used to slow down the corrosion rate of biomedical magnesium alloys. However, these coatings usually act only as passive barriers. It is much more desirable to endow such coatings with active, biocorrosion-responsive self-repairing capacity. In the present work, a self-healing coating system (denoted as "silk-PA") was constructed in the form of a sandwich architecture of fluoride precoating (bottom), silk-phytic acid (PA) coating (middle), and silk fibroin coating (top). Here, PA was loaded in the middle coating as a corrosion inhibitor by harnessing its strong chelating ability toward dissolving Mg2+ and Ca2+ ions. The self-healing property was evaluated by scratch and SVET tests, and the corrosion resistance was evaluated by in vitro immersion and electrochemical measurements. The results showed that the silk-PA manifested intriguing self-healing capacity with pH responsiveness, hence profiting the corrosion resistance of the Mg-1Ca alloy. The biocompatibility and osteogenic activity of the coating system were further evaluated using MC3T3-E1 cells, and it demonstrated favorable responses in multiple cellular behaviors, i.e., adherence, spreading, proliferation, and differentiation. These findings open new opportunities in the study of self-healing coatings for protection against corrosion in biomedical Mg alloys. STATEMENT OF SIGNIFICANCE: In the present study, a self-healing coating system with pH stimuli-responsiveness and osteogenic activity was fabricated on Mg-1Ca alloy by integrating a silk fibroin barrier coating, a silk fibrin/phytic acid composite coating, and a fluoride precoating. This coating system demonstrated interesting self-healing ability as compared to traditional surface modification layers. Furthermore, the self-healing ability enhanced the corrosion resistance of biomedical magnesium alloys, while effective compositions of the coating system endowed the substrate with osteogenic activity. This work provides some new insights into smart surface modification for biomedical Mg alloys.

Magnesium and its alloys have emerged as some of the most promising biodegradable metals for temporary bone implants, but challenges remain in controlling their corrosion and biocompatibility and endowing them with bioactivity and osteogenic functionality. Herein, we presented newly developed bioactive Ca, Sr/P-containing silk fibroin films (the Ca, Sr/P silk) on top of Mg-1Ca alloy to simultaneously improve the corrosion resistance, osteocompatibility, and osteogenic activities important in maintaining mechanical integrity and stimulating bone formation, respectively. Briefly, extracellular matrix (ECM) mimicking Ca, Sr/P silk fibroin films were constructed layer upon layer on fluoridized Mg-1Ca alloy via simple spinning assembly. The corrosion resistance property of different samples was studied in vitro by immersion experiments and electrochemistry measurements in Hanks' solution, with the silk-coated ones showing over 1 order of magnitude increase in corrosion resistance compared to the uncoated. Particularly, the Ca, Sr/P silk had the best anticorrosion performance, presumably because of better retaining of the β-sheet silk conformation and ion-induced structural conversion from random coils to silk I and α-helices. Furthermore, the preliminary study of the corrosion behavior of the Ca, Sr/P silk was confirmed the availability of the films for corrosion resistance improvement. The osteocompatibility and osteogenic activities were evaluated by the multiple osteoblast (MC3T3-E1) responses, i.e., proliferation, adherence, spreading, and differentiation in vitro. The Ca, Sr/P silk exhibited the optimal osteogenic activity among all experimental groups. These preliminary results comprehensively confirmed the validity of the coating strategy and they implicated the great potential of the modified Mg alloys as degradable bone implants.

Bioabsorbable magnesium alloys are becoming prominent materials for cardiovascular stents, as their desirable mechanical properties and favorable biosafety. However, the rapid corrosion of magnesium alloys under physiological conditions hinders their wider application as medical implant materials. Fluoride chemical conversion treatment is an effective and simple technique to improve the corrosion resistance for magnesium alloys. Despite previous literature reporting on fluoride chemical conversion treatment with hydrofluoric acid (HF) in different conditions, some defects are still present on the surface of the coating. In this study, we report on a two-step alkali-fluoride treatment of magnesium alloy by effectively removing the second phase in the substrate surface and form a dense and flawless magnesium fluoride (MgF

Several coarsening algorithms have been developed as a powerful strategy to deal with difficult machine learning problems represented by large-scale networks, including, network visualization, trajectory mining, community detection and dimension reduction. It iteratively reduces the original network into a hierarchy of gradually smaller informative representations. However, few of these algorithms have been specifically designed to deal with bipartite networks and they still face theoretical limitations that need to be explored. Specifically, a recently introduced algorithm, called MLPb, is based on a synchronous label propagation strategy. In spite of an interesting approach, it presents the following two problems: 1) A high-cost search strategy in dense networks and 2) the cyclic oscillation problem yielded by the synchronous propagation scheme. In this paper, we address these issues and propose a novel fast coarsening algorithm more suitable for large-scale bipartite networks. Our proposal introduces a semi-synchronous strategy via cross-propagation, which allows a time-effective implementation and deeply reduces the oscillation phenomenon. The empirical analysis in both synthetic networks and real-world networks shows that our coarsening strategy outperforms previous approaches regarding accuracy and runtime.

Tissue engineering method provides a promising solution for meniscus repair and regeneration. However, the inflammatory environment that persists after meniscus injury in the knee joint impedes meniscus tissue regeneration. The purpose of this study was to investigate the applicability of silk/graphene oxide (GO)-based meniscus scaffold modified with tannic acid (TA)/Sr

To overcome the restricted degradation, poor antiacterial and osteoindctive problems of magnesium and its alloys, this study presented the spinning coating of an antimicrobial peptide (AP)-loaded silk fibroin (SF) composite onto a corrosion-resistant MgO-coated AZ31 Mg alloy via anodization (aMgO) and electrodeposition (eMgO) methods. The composite coatings not only created a smooth and hydrophilic surface, but also obviously improved the corrosion resistance according to the test of corrosion potential and current density. The colonization of E. coli on MgO-AP composite coatings was significantly reduced as compared to the MgO layers, due to the potential synergetic effects of APs and Mg2+. Compared with the bare AZ31, the composite coating inhibited the corrosion of the substrate and the release of Mg2+, supported the adhesion, spreading and proliferation of osteoblasts, and presented a significantly improved osteogenic differentiation trend. Therefore, the MgO-AP composite coating, which had both antibacterial and bone-promoting abilities, was expected to be applied for surface modification of magnesium alloy implants to solve the clinical problems of bacterial infection and poor osseointegration.

Osteoporosis is an increasing public health problem in the worldwide and has caused socioeconomic burden. Natural products as candidates have the potential to promote bone formation and suppress bone resorption for osteoporosis treatment. Previously, syringin has showed the potent anti-osteoporosis activity, however the detailed mechanism of syringin against osteoporosis is still unclear. This study aimed to reveal the pharmacological effect and mechanism of syringin through the high-throughput metabolomics. In this study, metabolomics techniques were used to explore the metabolic biomarkers and profiles provides deep insights into the pharmacological effects and mechanism of syringin against osteoporosis. The metabolite biomarkers were monitored based on the high-resolution mass spectrometry. By the integration analysis of metabolomics technology, a total of 23 metabolic biomarkers were discovered and we found the highly relevant pathway involved in glycine and serine metabolism, butyrate metabolism, methionine metabolism, catecholamine biosynthesis, tyrosine metabolism, etc. Interestingly, synthesis and degradation of ketone bodies, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, tyrosine metabolism, glycine, serine and threonine metabolism, butanoate metabolism, was related with efficacy of syringin. The present work showed that the metabolomics technology can provide novel strategies for revealing insights into the metabolic effects and action mechanism of drug.

Polyetheretherketone has been widely used for bone defect repair, whereas failures may happen due to implant loosening and infection. Thus, PEEK implant with multi-function (osteogenesis, angiogenesis, and bacteria-killing) is essential to solve this problem. Herein, copper oxide microspheres (µCuO) decorated with silver nanoparticles (nAg) were constructed on porous PEEK surface via silk fibroin. In vitro studies highlighted the pH controlled release ability of this coating. It liberated a high dose of Cu2+ and Ag+ at low pH environment (pH 5.0), leading to 99.99% killing of planktonic bacteria and complete eradication of sessile bacteria, avoiding biofilm formation. Under physiological environment (pH 7.4), a lower amount of leaked metal ions induced promoted ALP production, collagen secretion, and calcium deposition, as well as NO production, which indicated potentiated osteogenesis and angiogenesis. In vivo results displayed the highest new bone volume around, and the appearance of new bone inside porous structure of, PEEK implant with this coating in rabbit tibia, signified the abilities of this coating to promote bone regeneration and osseointegration. Our study established solid support for implants with this coating to be a successful bone defect repair solution. STATEMENT OF SIGNIFICANCE: In this study, CuO/Ag micro/nano particles were incorporated into the porous surface of PEEK through polydopamine and silk fibroin layers. The design of this coating conferred pH-controlled release behavior to Cu2+ and Ag+. High dose of metal ions were released at pH 5.0, which presented synergistic antibacterial ability and killed 99.99% of planktonic bacteria. Low concentration of metal ions were controlled by this coating at physiological environment, which potentiated osteodifferentiation of Ad-MSC in vitro and led to complete integration of implant with bone tissue in vivo.

Polyetheretherketone has been widely used for bone defect repair, whereas failures may happen due to implant loosening and infection. Thus, PEEK implant with multi-function (osteogenesis, angiogenesis, and bacteria-killing) is essential to solve this problem. Herein, copper oxide microspheres (μCuO) decorated with silver nanoparticles (nAg) were constructed on porous PEEK surface via silk fibroin. In vitro studies highlighted the pH controlled release ability of this coating. It liberated a high dose of Cu2+ and Ag+ at low pH environment (pH 5.0), leading to 99.995% killing of planktonic bacteria and complete eradication of sessile bacteria, avoiding biofilm formation. Under physiological environment (pH 7.4), a lower amount of leaked metal ions induced promoted ALP production, collagen secretion, and calcium deposition, as well as NO production, which indicated potentiated osteogenesis and angiogenesis. In vivo results displayed the highest new bone volume around, and the appearance of new bone inside porous structure of, PEEK implant with this coating in rabbit tibia, signified the abilities of this coating to promote bone regeneration and osseointegration. Our study established solid support for implants with this coating to be a successful bone defect repair solution.

Biomedical device-associated infections (BAI) and osteosynthesis are two main complications following the orthopedic implant surgery, especially while infecting bacteria form a mature biofilm, which can protect the organisms from the host immune system and antibiotic therapy. Comparing with the single antibiotics therapeutic method, the combination of silver nanoparticles (AgNPs) and conventional antibiotics exert a high level of antibacterial activity. Nevertheless, one major issue that extremely restricts the potential application of AgNP/antiviotics is the uncontrolled release. Moreover, the lack of osteogenic ability may cause the osteosynthesis. Thus, herein we fabricated a structure-controlled drug-loaded silk fibroin (SF) coating that can achieve the size and release control of AgNPs and high efficient osteogenesis. Three comparative SF-based coatings were fabricated: α-structured coating (α-helices 32.7%,), m-structured coating (β-sheets 28.3%) and β-structured coating (β-sheets 41%). Owning to the high content of α-helices structure and small AgNPs (20 nm), α-structured coating displayed better protein adsorption and hydrophilicity, as well as pH-dependent and long-lasting antibacterial performance. In vitro studies demonstrated that α coating showed good biocompatibility (cellular attachment, spreading and proliferation), high ALP expression, collagen secretion and calcium mineralization. Moreover, after one month subcutaneous implantation in vivo, α-structured coating elicited minimal, comparable inflammatory response. Additionally, in a rabbit femoral defect model, α-structured coating displayed a significant improvement on the generation of new-born bone and bonding between the new bone and the tissue, implying a rapid and durable osteointegration. Expectedly, this optimized structure-controlled SF-based coating can be an alternative and prospective solution for the current challenges in orthopedics.

Because of the increasing use of biomedical implants, implants associated infections are becoming more prevalent and cause increased morbidity and significant higher healthcare cost. As it is a race for the surface between cells and microbes, achieving a rapid bone regeneration and osseointegration, especially when confronted with implants associated infections, is the primary goal. Herein, we develop a promising solution using porous polyetheretherketone (PEEK) implants incorporated with copper-citrate nanoclusters via bioinspired polydopamine, it can deliver a high dose of bactericides only when and where bacteria appear to eradicate bacteria and release a small amount of copper/citrate under physiological environment to promote osteogenesis and angiogenesis in vitro and in vivo. The synergistic effect between copper and citrate, which is that citrate can facilitate a 2-fold influx of copper into cells, not only heightened the bacteria-killing ability but also encouraged the osteogenesis and angiogenesis performances of implants. This present work provides an effective method to control infections while promoting osseointegration simultaneously, which will show tremendous clinical application and can be a solution to current challenges facing orthopedics.

Biomedical associated infections (BAI) are difficult to treat and may even lead to amputation and death, especially after the emergence of drug-resistant bacteria. The aim of this study was to harness the potential synergistic effects of multiple bactericidal agents to endow polyetheretherketone (PEEK) with the ability of achieving full eradication of planktonic and adherent bacteria while maintaining acceptable biocompatibility. In this work, a mussel inspired, silver nanoparticles (AgNPs) incorporated silk fibroin (SF)/gentamicin sulfate (GS) coating was constructed upon porous PEEK surface. The obtained coating greatly enhanced the bactericidal efficiency to Gram-positive bacteria and Gram-negative bacteria. The number of bacteria survived in the culture medium after treated with this coating was 106 fold lower than that survived after treated with PEEK sample, while the number of viable bacteria adhered to this coating was 105 lower than that adhered to PEEK sample. Furthermore, release of Ag+ and GS increased with decreasing pH, indicating great potential of this coating to be a “smart” bacteria-triggered self-defensive coating. Meanwhile, this functional coating shows favorable cytocompatibility and osteogenic ability. The mechanism behind this dual function is also partially revealed. Expectedly, this “smart” dual function coating can give a promise for PEEK to become a solution to increasingly deteriorated BAI. Statement of Significance In this study, a mussel inspired, silver nanoparticles (AgNPs) incorporated silk fibroin (SF)/gentamicin sulfate (GS) coating was constructed upon porous polyetheretherketone (PEEK) surface. This design was aimed to provide a solution to the increasingly deteriorated biomedical associated infections (BAI). Actually, this design endowed PEEK with dual function: bacteria-triggered synergistic bactericidal effect and improved osteogenic ability. The combination of silver and GS exhibited synergistic bacteria killing effect on both Gram-positive and Gram-negative bacteria, which showed 106 times higher in releasing-killing and 105 times higher in anti-adhesion than that of untreated PEEK. Furthermore, release of bactericidal agents increased with decreasing pH, indicating great potential of this coating to be a bacteria-triggered self-defensive coating. More interestingly, this study revealed the mechanism of synergistic effect between silver and GS.

Biomaterials-enabled regenerative medicine in orthopedics is challenged with infective bone defects that do not heal normally. Three-dimensional (3D) scaffold biomaterials simultaneously emulating skeletal hierarchy and eliciting sustainable osteogenetic and antibacterial functionalities represent a potent solution holding increasing fascination. Here we describe a simple combinatorial strategy for constructing such scaffolds. Fully porous titanium was first tailor-made by metallic powder 3D printing and subjected to in situ hydrothermal growth of a micro/nanostructured titanate layer, to which nanosilver encapsulated, physically cross-linked silk fibrin multilayer films were anchored through polydopamine-assisted, silk-on-silk self-assembly. The hydrophilicity, protein adsorption, and surface bioactivity of the scaffolds were investigated. Employing clinically relevant pathogenic Staphylococcus aureus bacteria, we tested that the silver immobilized scaffolds not only reduced adherence of bacteria on the ...

To endow orthopaedic implants with satisfactory antibacterial properties, the design and development of antibiotic coating on the surface of implants is highly desired. In this work a novel and facile strategy was developed to form pH-responsive layer-by-layer (LbL) films implanted with polymeric micelles as nano-vehicles loaded with charge-weak antibiotic drugs, enabling high drug loading efficiency. Negatively charged tobramycin (Tob)-embeded heparin miscells (HET) and positively charged chitosan (CHT) were exploited as a pH-responsive LBL multilayer building block, respectively. The formation mechanism and pH-stimulated release behavior of the Tob-contained heparin micelles were studied. The characterization on the morphologies, chemical compositions and hydrophilicity of the modified surface confirmed the successuful deposition of the Tob-loaded CHT/HET multilayers coatings on the polydopamine-modified Ti surface. The drug release profiles displayed fast release at pH 7.4 and slow release after exposure to weakly acidic environments. Antibacterial tests indicated that the Tob-embed CHT/HET nanostructured multilayers not only strongly inhibited initial bacterial adhesion, but also disruptted biofilm formation. Particularly, this functional coatings showed “long-term antibacterial” pattern in acid condition. Meanwhile, MC3T3 cells showed acceptable adhesion, spread and proliferation on the multilayer coatings in cytocompatible studies. In a word, these multilayer coatings incorporated with a wide variety of antibiotics show promisiong applications in preventing postoperative infection and resolving unmet clinical need.

Enhanced antiinfection activities, improved hemocompatibility and osteo-compatibility, and reinforced osseointegration are among the most important considerations in designing multifunctional orthopedic biomaterials. Hereby, anti-infective and osteogenic multifunctional 3D printed porous Ti6Al4V implant with excellent hemocompatibility was successfully designed and fabricated. In brief, osteogenic micro-arc oxidation (MAO) coatings with micro/nanoscale porous topography were generated in situ on 3D printed Ti6Al4V scaffolds, on which heparin and vancomycin were easily immobilized. The surface microstructure, morphology, and chemical compositions were characterized employing scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). High loading capacity and sustained vancomycin release profiles were revealed using high performance liquid chromatography (HPLC). Favorable antibacterial and antibiofilm performances against pathogenic Staphylococcus aureus ( S. aureus ) were validated in vitro through microbial viability assays, Live/Dead bacterial staining, and crystal violet staining. Human mesenchymal stem cells (hMSCs) were seeded on the scaffolds and their proliferation and viability were assessed using Cell Counting Kit and Live/Dead cell viability kit. Further, osteoblastic differentiation abilities were evaluated using alkaline phosphatase (ALP) activity as a hall marker. Additionally, the improved hemocompatibility of the heparinized scaffolds was confirmed by activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). Overall, our results show that the surface-modified 3D printed porous Ti6Al4V possesses balanced antibacterial and osteogenic functions while exhibiting extra anticlotting effects, boding well for future application in customized functional reconstruction of intricate bone defects.

Vascular stent interventional therapy, as a regular and effective therapy, has been widely used to treat coronary artery diseases. However, adverse events occur frequently after stent intervention, especially restenosis and late stent thrombosis. The targeted implanting site will suffer from severe atherosclerosis, which is considered as a chronic inflammatory disease. Meanwhile, with the over-expanding use of endovascular mechanical intervention, vascular injury has become an increasingly common issue. Lesions and newly induced vascular injury result in inflammatory and oxidative stress; meanwhile, activated macrophages and granulocytes generate high levels of reactive oxygen species (ROS), contributing to endothelial dysfunction and neointima hyperplasia. Therefore, attenuating oxidative stress and reducing ROS generation in the inflammatory response represent reasonable strategies to inhibit intimal hyperplasia and restenosis. Herein, we have developed a multifunctional surface for the MgZnYNd alloy with tannic acid (TA) coating, and the pH dependence of the coating deposition is also demonstrated. The phenolic hydroxyl groups on the coatings endow the modified surface with excellent antioxidant functions. We found that the coating can be recycled, and the scavenging activity hardly weakened within five cycles. Also, the TA coating has a promising strong antioxidant activity as it shows a radical scavenging activity over 80% in long term. Moreover, the TA coating possesses platelet-repellent capability. No significant inflammatory response was observed for the TA modified sample in the rat subcutaneous implantation test. Combining these performances, we envision that the vascular stent modified with TA coating can have great potential in various applications by virtue of its simplicity and effectiveness.

Tracheobronchial obstruction in children due to benign stenosis or tracheobronchomalacia still remains a challenging matter of concern. Currently, there is 10%–20% complication rate in clinical treatment. The non-biodegradable property of silicone stents and nickel-titanium memory alloy stents take the primary responsibility for drawbacks including stimulating local granulation tissue proliferation, displacement, and stent-related infections. Permanent tracheobronchial stent will be a persistent foreign object for a long time, causing excessive secretion of tracheal mucosa, ulceration and even perforation, which is particularly unsuitable for young children with persistent tracheal growth. In this study, the degradation and biocompatibility performance of three typical biodegradable metals were investigated as potential tracheobronchial stent materials. The results exhibited that these materials showed different degradation behaviors in the simulating respiratory fluid environment compared with SBF. Except for pure iron group, high purity magnesium and zinc showed favorable cell adhesion and proliferation in three culture methodologies (direct culture, indirect culture and extraction culture). The proper corrosion rate and good biocompatibility indicated that high purity magnesium and zinc may be good candidates as tracheobronchial stent materials., Graphical abstract Image 1, Highlights • Much slower corrosion rate was obtained in Gamble's solution simulating the respiratory fluid environment. • Cell culture methodologies including direct culture, indirect culture and extraction culture influences cell morphologies and cell growth. • The corrosion rate and biocompatibility assessment indicated that high purity magnesium and zinc may be good candidates as tracheobronchial stent materials.

Coating bioceramics of inherent bioactivity onto biometallic implants is a straightforward yet promising solution to address poor osteointegration of the latter. One step further, it would be a nontrivial accomplishment to develop a mild, cheap, and universal route to firmly stabilizing, in principle, any ceramics onto any implant substrate, while imparting expectedly versatile biofunctional performances. Herein, we describe a triple-bioinspired burying/cross-linking interfacial coassembly strategy for enabling such ceramic coatings, which ingeniously fuses bioinspiration from sea rocks (burying assisted particle immobilization), marine mussels (universal adhesion and versatile chemical reactivity), and reef-building oysters (cross-linking rendered cohesion). Specifically, surface functionalized, aqueous dispersed ceramic particles were buried within an substrate-anchored organic matrix of polyelectrolyte multilayers (i.e., (poly(ether imide) (PEI)/poly(sodium-p-styrenesulfonate) (PSS))n), through a new i...

Core-shell nanoparticles (CSNs) have numerous intriguing properties for advanced device applications, while it remains challenging to directly grow them from a solid substrate. Here, we report a simple mussel-bioinspired solid chemistry strategy for in-situ synthesis of CSNs that are substrate anchored and morphologically tunable for wide-ranging biotechnological applications. Briefly, silver titanate was hydrothermally grown on template titanium and subjected to reaction with mussel-derived dopamine. The synergistic reactivity between silver titanate and dopamine prompted nanosilver/polydopamine (nAg/PD) CSNs to spontaneously assemble and grow on substrate. These CSNs possessed reaction time-dependent dimensions and morphologies, which were related to differing physiochemical properties and biological behaviors. Specifically, the CSNs-modified substrates demonstrated enhanced protein affinity and durable radical scavenging properties. In addition, they manifested remarkable yet robust release-killing and anti-biofilm activities against pathogenic Staphylococcus aureus bacteria. More delightedly, the surface-engineered substrates guaranteed the victory of the anti-infective battle of osteoblastic cells during cell/bacteria coculture, promising applications in implantable medical devices. The adaptability of this strategy was demonstrated by modifying complicated 3D-printed macroporous tissue engineering scaffolds. Intriguingly, the CSNs-modified scaffolds exhibited photothermal performances that bode well for phototherapy. To sum, our strategy combines the simplicity of synthesis modality, the controllability of core-shell silver structures, and the versatility of material functions. The resulting assemblies can enrich the library of nAg-based core-shell engineered nanomaterials.

To solve the Ti implants-associated infection and poor osseointegration problems, we have constructed the AgNPs/gentamicin (Gen)-loaded silk fibroin (SF) coating with acceptable antibacterial and osteogenic aptitude. Nevertheless, due to uncontrollably sustained drug release, this bactericidal coating encountered some tricky problems, such as local high Ag concentration, short life-span and potential cytotoxicity. In this work, a chitosan (CS) barrier layer was constructed to prebuilt the SF-based film by two means, dip-coating (DCS) and spin-coating (SCS). Intriguingly, the CS barrier layer constructed by spin-coating highly improved the hydrophilic and protein-absorbed performances. As verified in the release profile, both coatings showed a prolonged and pH-dependent pattern of Ag+ with an accelerated release in acidic condition. Also, the multilayer coating with a SCS barrier layer showed an apparent bacteria-trigged antibacterial and biofilm-inhibited performances, whereas the improvements of antibacterial abilities of DCS coating were limited. The mechanisms could be explained that the pH decrease induced by the attachment and proliferation of bacteria triggered collapse of CS barrier layer, accelerating the release of bactericides. Moreover, benefitted from pH-dependent release behavior of Ag and bioactive SCS layer, functional coatings highly enhanced the initial adhesion, migration and proliferation of preosteoblast MC3T3-E1 cells, and subsequently accelerated osteoblast differentiation (alkaline phosphatase production). A relevant aspect of this work was to demonstrate the essential effect of reasonable construction of self-defensive barrier layer in achieving the balance between the high-efficiency bacterial killing and osteogenic activity, and highlighted its excellent potential in clinical applications.

This study aimed to investigate the relationship between the immobilization efficiency of heavy metals (HMs) and the generation of bio-gas under different catalyzing conditions during the supercritical water gasification of sludge. Results showed that catalysts could promote the decomposition of organic matters to improve the yield of bio-gas and the order of the catalysts in terms of H2 selectivity was Pd > CaO > AlCl3. Pd catalyst not only promoted the generation of hydrogen-rich bio-gas but also enhanced the immobilization efficiency of HMs. This was because the Pd catalyst facilitate the steam reforming reaction of the high-molecular-weight organic matters while promoting the combination of HMs with mineral components to form stable crystalline compounds. When the addition amount of Pd catalyst was 10 wt %, the yield of hydrogen-rich bio-gas increased from 35.74 wt% to 46.88 wt%, and the leaching concentration of Zn, Cu, and Cr decreased significantly to 1.22 mg/L, 0.55 mg/L and 0.38 mg/L, respectively. In addition, rational adjustment of addition amount of catalyst could optimize the specific surface area of the bio-char to enhance the physical adsorption of HMs via affecting the process of bio-gas generation.

With the progressively increasing demand for orthopedic Ti implants, the balance between two primary complications restricting implant applications is needed to be solved: the lack of bone tissue integration and biomedical device-associated infections (BAI), where emergence of multiresistance bacteria make it worse. Notably, a combination of silver nanoparticles (AgNPs) and a kind of antibiotic can synergistically inhibit bacterial growth, where a low concentration of AgNPs has been confirmed to promote the proliferation and osteogenesis of osteoblasts. In this work, we built AgNPs/gentamicin (Gen)-embedded silk fibroin (SF)-based biomimetic coatings on orthopedic titanium by a facile dipping–drying circular process and with the assistance of polydopamine (PD). Ag+ was reduced to AgNPs by SF under ultraviolet (UV) irradiation, and then they were detected by transmission electron microscope (TEM) images and UV–visible (UV–vis) analyses. Intriguingly, the addition of Gen highly improved the reduction effici...

The immobilization effects and mechanism of heavy metals (Cr, Cu, Zn, Cd, Ni and Pb) in the process of original sludge pyrolysis by single-mode microwave have been investigated in the study, and immobilization effects and mechanism of heavy metals were compared by doping different additives such as Sic, graphite and sludge residues into sludge. The in situ immobilization effects of different microwave absorbing substances on the sludge were compared by Toxicity Characteristic Leaching Procedure (TCLP) and Synthetic Precipitation Leaching Procedure (SPLP) and the results showed that in-situ microwave-assisted pyrolysis can effectively immobilize Cr, Cu, Zn, Cd, Ni and Pb in the sludge, with leaching concentration reduced by 68.3% to 94.59%. Of them, the leaching concentration of sludge doped with pyrolysis residues reduced by 85.20%. The heavy metals speciation in the original sludge and the sludge with doping additives treated by microwave, were analyzed by sequential extraction procedure of Tessier, showing that the speciation of heavy metals treated by microwave turned into the most stable residue form.