Near-infrared light responsive gold nanoparticles coating endows polyetheretherketone with enhanced osseointegration and antibacterial properties.

Polyetheretherketone (PEEK) is considered as a promising dental implant material owing to its excellent physicochemical and mechanical properties. However, its wide range of applications is limited by its biologically inert nature. In this study, a near-infrared (NIR) light responsive bioactive coating with gold nanoparticles (AuNPs) and metronidazole adhered to the PEEK surface via dopamine polymerization. Compared to pure PEEK, the hydrophilicity of the treated PEEK surface was significantly improved. In addition, under NIR light, the surface coating exhibited photothermal conversion effect, and gold nanoparticles and the antibiotic can be released from the coating. This improved the antibacterial properties of PEEK materials. Moreover, the coating was more conducive to the early adhesion of bone mesenchymal stem cells. The results of in vitro and in vivo osteogenic activity studies showed that the developed coating promoted osseointegration of PEEK implants, and NIR light irradiation further improved the antibacterial ability and osteogenic activity of PEEK implants. Through RNA sequencing, the potential underlying mechanism of promoting bone formation of the AuNPs coating combined metronidazole was interpreted. In summary, the developed coating is a potential surface treatment strategy that endows PEEK with enhanced osseointegration and antibacterial properties.

Single-cell coating with biomimetic extracellular nanofiber matrices.

Cell therapies offer great promise in the treatment of diseases and tissue regeneration, but their clinical use has many challenges including survival, optimal performance in their intended function, or localization at sites where they are needed for effective outcomes. We report here on a method to coat a biodegradable matrix of biomimetic nanofibers on single cells that could have specific functions ranging from cell signaling to targeting and helping cells survive when used for therapies. The fibers are composed of peptide amphiphile (PA) molecules that self-assemble into supramolecular nanoscale filaments. The PA nanofibers were able to create a mesh-like coating for a wide range of cell lineages with nearly 100 % efficiency, without interrupting the natural cellular phenotype or functions. The targeting abilities of this system were assessed in vitro using human primary regulatory T (hTreg) cells coated with PAs displaying a vascular cell adhesion protein 1 (VCAM-1) targeting motif. This approach provides a biocompatible method for single-cell coating that does not negatively alter cellular phenotype, binding capacity, or immunosuppressive functionality, with potential utility across a broad spectrum of cell therapies. STATEMENT OF SIGNIFICANCE: Cell therapies hold great promise in the treatment of diseases and tissue regeneration, but their clinical use has been limited by cell survival, targeting, and function. We report here a method to coat single cells with a biodegradable matrix of biomimetic nanofibers composed of peptide amphiphile (PA) molecules. The nanofibers were able to coat cells, such as human primary regulatory T cells, with nearly 100 % efficiency, without interrupting the natural cellular phenotype or functions. The approach provides a biocompatible method for single-cell coating that does not negatively alter cellular phenotype, binding capacity, or immunosuppressive functionality, with potential utility across a broad spectrum of cell therapies.

Complex network-based classification of radiographic images for COVID-19 diagnosis.

In this work, we present a network-based technique for chest X-ray image classification to help the diagnosis and prognosis of patients with COVID-19. From visual inspection, we perceive that healthy and COVID-19 chest radiographic images present different levels of geometric complexity. Therefore, we apply fractal dimension and quadtree as feature extractors to characterize such differences. Moreover, real-world datasets often present complex patterns, which are hardly handled by only the physical features of the data (such as similarity, distance, or distribution). This issue is addressed by complex networks, which are suitable tools for characterizing data patterns and capturing spatial, topological, and functional relationships in data. Specifically, we propose a new approach combining complexity measures and complex networks to provide a modified high-level classification technique to be applied to COVID-19 chest radiographic image classification. The computational results on the Kaggle COVID-19 Radiography Database show that the proposed method can obtain high classification accuracy on X-ray images, being competitive with state-of-the-art classification techniques. Lastly, a set of network measures is evaluated according to their potential in distinguishing the network classes, which resulted in the choice of communicability measure. We expect that the present work will make significant contributions to machine learning at the semantic level and to combat COVID-19.

Antibacterial Properties of Gold Nanoparticles in the Modification of Medical Implants: A Systematic Review.

The widespread occurrence of bacterial infections and their increased resistance to antibiotics has led to the development of antimicrobial coatings for multiple medical implants. Owing to their desirable properties, gold nanoparticles (AuNPs) have been developed as antibacterial agents. This systematic investigation sought to analyze the antibacterial effects of implant material surfaces modified with AuNPs. The data from 27 relevant studies were summed up. The included articles were collected from September 2011 to September 2021. According to the retrieved literature, we found that medical implants modified by AuNPs have good antibacterial effects against gram-positive and gram-negative bacteria, and the antibacterial effects would be improved by near-infrared (NIR) radiation.

High-throughput metabolomics using UPLC/Q-TOF-MS coupled with multivariate data analysis reveals the effect and mechanism of syringin against ovariectomized osteoporosis.

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.

Mussel bioinspired morphosynthesis of substrate anchored core-shell silver self-assemblies with multifunctionality for bioapplications.

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.

Tannic acid/Sr2+-coated silk/graphene oxide-based meniscus scaffold with anti-inflammatory and anti-ROS functions for cartilage protection and delaying osteoarthritis.

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.

Based on the synergistic effect of Mg2+ and antibacterial peptides to improve the corrosion resistance, antibacterial ability and osteogenic activity of magnesium-based degradable metals.

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.

In vitro and in vivo evaluation of structurally-controlled silk fibroin coatings for orthopedic infection and in-situ osteogenesis.

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 (ß-sheets 28.3%) and ß-structured coating (ß-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 ß-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.

pH-responsive silk fibroin-based CuO/Ag micro/nano coating endows polyetheretherketone with synergistic antibacterial ability, osteogenesis, and angiogenesis.

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.

Cell-free 3D wet-electrospun PCL/silk fibroin/Sr2+ scaffold promotes successful total meniscus regeneration in a rabbit model.

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.

In vitro degradation and biocompatibility evaluation of typical biodegradable metals (Mg/Zn/Fe) for the application of tracheobronchial stenosis.

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.

A tannic acid-modified fluoride pre-treated Mg-Zn-Y-Nd alloy with antioxidant and platelet-repellent functionalities for vascular stent application.

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.

Osteogenic and pH stimuli-responsive self-healing coating on biomedical Mg-1Ca alloy.

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.

A pH-sensitive self-healing coating for biodegradable magnesium implants.

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.

Triple-Bioinspired Burying/Crosslinking Interfacial Coassembly Strategy for Layer-by-Layer Construction of Robust Functional Bioceramic Self-Coatings for Osteointegration Applications.

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 inorganic-organic hybrid layer-by-layer (LBL) coassembly scheme wherein mussel (oyster) inspired adhesive (cohesive) chemistries were exquisitely orchestrated. As a conceptual demonstration, bioactive baghdadite (Ca3ZrSi2O9) was synthesized as model ceramics, with which we constructed on medical titanium robust, biomimetic, and cross-linkable LBL self-assemblies harnessing the said strategy. Intimate substrate contacts and well-defined buried inorganic-organic interfaces were evidently seen, together with good structural and chemical stabilities, especially after cross-linking. Sustained bioactive ion releasing and appreciable biomineralization activity were confirmed in vitro. Subsequently, biological performances of the assemblies were systematically investigated with respect to surface hydrophilicity, protein adsorption, and osteoblast functions. Additionally, nanosilver deposition, which imparted the surfaces with added antibacterial potencies, was used to exemplify the strategy's versatility in allowing multifunctionality. What's more, the flexibility of our approach was testified through modifying clinically relevant complicated 3D porous scaffolds. Overall, our strategy basically met the design expectations, boding well for future medical adoption. This study offers the promise of an alternative broadly useful avenue to bioactive and functional surface design of bone implants. It may also provide insights into other multiple-bioinspired materials/interfaces for biological and other applications.

In Vitro and in Vivo Studies on Two-Step Alkali-Fluoride-Treated Mg-Zn-Y-Nd Alloy for Vascular Stent Application: Enhancement in Corrosion Resistance and Biocompatibility.

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 (MgF2) coating to endow the magnesium alloy greater corrosion resistance. The results showed that the serious pitting corrosion caused by galvanic corrosion could be effectively prevented after removing of the second phase of the surface. In vivo tests in a rat subcutaneous implantation model showed that two-step alkali-fluoride-treated MgZnYNd alloy (MgZnYNd-A-F) uniformly corroded with a low corrosion rate. No subcutaneous gas cavities or significant inflammatory cell infiltration were observed for MgZnYNd-A-F in in vivo tests. The two-step alkali-fluoride treatment can significantly improve the corrosion resistance and biocompatibility of magnesium alloy, which has great potential in the application of vascular stents because of its simplicity and effectiveness.

Constructing Multilayer Silk Protein/Nanosilver Biofunctionalized Hierarchically Structured 3D Printed Ti6Al4 V Scaffold for Repair of Infective Bone Defects.

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 surface, they also actively killed those planktonic, and these performances were largely maintained over an extended period of 6 weeks. Additionally, our engineered scaffolds were amenable to 14 days' continuous, intense bacterial attacks showing little sign of biofilm colonization, and they were interestingly capable of eradicating bacteria in already formed biofilms. High cargo loading, durable topical Ag+ release, and overwhelming oxidative stress were shown to contribute to this sustainable antibacterial system. Irrespective of certain degree of cellular stress at early stages, our scaffolds elicited generally enhanced cell proliferation, alkaline phosphatase enzyme production, and matrix calcification of osteoblastic MC3T3-E1. These multifunctionalities, coupled with the design freedom, shape flexibility, and cost-effectiveness offered by 3D printing, make our scaffold biomaterials a promising option for customized restoration of complicated infective bone defects.

Endowing polyetheretherketone with synergistic bactericidal effects and improved osteogenic ability.

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.