In Situ Disinfection through Photoinspired Radical Oxygen Species Storage and Thermal-Triggered Release from Black Phosphorous with Strengthened Chemical Stability.

Photodynamic therapy (PDT) utilizing light-induced reactive oxygen species (ROS) is a promising alternative to combat antibiotic-resistant bacteria and biofilm. However, the photosensitizer (PS)-modified surface only exhibits antibacterial properties in the presence of light. It is known that extended photoirradiation may lead to phototoxicity and tissue hypoxia, which greatly limits PDT efficiency, while ambient pathogens also have the opportunity to attach to biorelevant surfaces in medical facilities without light. Here, an antimicrobial film composed of black phosphorus nanosheets (BPSs) and poly (4-pyridonemethylstyrene) endoperoxide (PPMS-EPO) to control the storage and release of ROS reversibly is introduced. BPS, as a biocompatible PS, can produce high singlet oxygen under the irradiation of visible light of 660 nm, which can be stably stored in PPMS-EPO. The ROS can be gradually thermally released in the dark. In vitro antibacterial studies demonstrate that the PPMS-EPO/BPS film exhibits a rapid disinfection ability with antibacterial rate of 99.3% against Escherichia coli and 99.2% against Staphylococcus aureus after 10 min of irradiation. Even without light, the corresponding antibacterial rate reaches 76.5% and 69.7%, respectively. In addition, incorporating PPMS significantly improves the chemical stability of the BPS.

In vitro study on an antibacterial Ti-5Cu alloy for medical application.

Health of human beings is subjected to severe threats from the spread of harmful bacteria and the implant-associated infection remains a serious problem in clinic. In this study, a copper-bearing antibacterial titanium alloy, Ti-5Cu, has been developed for dental and orthopedic implant applications. The microstructure, mechanical property, electrochemical corrosion behavior, in vitro antibacterial performance, cytocompatibility and hemocompatibility of the alloy are systematically investigated. The results reveal that the Ti-5Cu alloy which consists of α-phase matrix and intermetallic compound Ti2Cu not only possesses strong antibacterial activity against both E. coli and S. aureus, but also exhibits better mechanical properties than the commercial pure titanium. It is confirmed that the release of trace amount of Cu ions from the alloy plays an important role in killing bacteria. In spite of the ion release, Ti-5Cu alloy still reveals excellent corrosion resistance. Moreover, good cytocompatibility and superior hemocompatibility make Ti-5Cu alloy to be a potential solution that could prevent the peri-implant infection in dental and orthopaedic applications.

Magnesium with micro-arc oxidation coating and polymeric membrane: an in vitro study on microenvironment.

Numerous modification methods have been reported to enhance the corrosion resistance of magnesium with positive results. However, little attention has been paid on their impact on micro-environment, particularly the ion concentration and local pH value. In this study, two different coatings were prepared on magnesium, one with porous micro-arc oxidation (MAO) coating alone, and the other with additional polymer polyhydroxybutyrate (PHB) membrane using spinning technique. Their in vitro corrosional and biological behaviors were investigated and compared. Both coatings were found to reduce the degradation rate of magnesium, but an additionally deposited PHB membrane was superior to MAO-coated magnesium since it could produce a micro-environment with preferable local pH value and ion concentration for osteoblast proliferation. Our study suggests that micro-environment should be another critical issue in evaluation of a modification method for orthopaedic implants.

Taurine-induced fabrication of nano-architectured conducting polypyrrole on biomedical titanium.

In this article, taurine, one of the small biomolecules associated with bone metabolism, is firstly utilized to induce the fabrication of nano-architectured conducting polypyrrole (NCPPy) on biomedical titanium in diverse pH values of phosphate buffer solution (PBS). Accordingly, the possible mechanism for the fabrication of NCPPy is proposed, which is dependent on the states of polytaurine from the polymerization of taurine, i.e., the inability of forming polytaurine and unordered restricted space results in taurine-incorporated and polytaurine-incorporated tightly packed nanoparticles (pH 6.2 and 8.0), respectively, and however, ordered restricted space constructed by polytaurine chains induces the fabrication of polytaurine-incorporated nanopillars (pH 6.8) and polytaurine-incorporated nanowire networks (pH 7.4).

Tailored Physicochemical Cues Direct Human Mesenchymal Stem Cell Differentiation through Epigenetic Regulation Using Colloidal Self-Assembled Patterns.

The extracellular matrix (ECM) shapes the stem cell fate during differentiation by exerting relevant biophysical cues. However, the mechanism of stem cell fate decisions in response to ECM-backed complex biophysical cues has not been fully understood due to the lack of versatile ECMs. Here, we designed two versatile ECMs using colloidal self-assembly technology to probe the mechanisms of their effects on mechanotransduction and stem cell fate regulation. Binary colloidal crystals (BCC) with a hexagonally close-packed structure, composed of silica (5 µm) and polystyrene (0.4 µm) particles as well as a polydimethylsiloxane-embedded BCC (BCCP), were fabricated. They have defined surface chemistry, roughness, stiffness, ion release, and protein adsorption properties, which can modulate the cell adhesion, proliferation, and differentiation of human adipose-derived stem cells (hASCs). On the BCC, hASCs preferred osteogenesis at an early stage but showed a higher tendency toward adipogenesis at later stages. In contrast, the results of BCCP diverged from those of BCC, suggesting a unique regulation of ECM-dependent mechanotransduction. The BCC-mediated cell adhesion reduced the size of the focal adhesion complex, accompanying an ordered spatial organization and cytoskeletal rearrangement. This morphological restriction led to the modulation of mechanosensitive transcription factors, such as c-FOS, the enrichment of transcripts in specific signaling pathways such as PI3K/AKT, and the activation of the Hippo signaling pathway. Epigenetic analyses showed changes in histone modifications across different substrates, suggesting that chromatin remodeling participated in BCC-mediated mechanotransduction. This study demonstrates that BCCs are versatile artificial ECMs that can regulate human stem cells' fate through unique biological signaling, which is beneficial in biomaterial design and stem cell engineering.

A mechanical-assisted post-bioprinting strategy for challenging bone defects repair.

Bioprinting that can synchronously deposit cells and biomaterials has lent fresh impetus to the field of tissue regeneration. However, the unavoidable occurrence of cell damage during fabrication process and intrinsically poor mechanical stability of bioprinted cell-laden scaffolds severely restrict their utilization. As such, on basis of heart-inspired hollow hydrogel-based scaffolds (HHSs), a mechanical-assisted post-bioprinting strategy is proposed to load cells into HHSs in a rapid, uniform, precise and friendly manner. HHSs show mechanical responsiveness to load cells within 4 s, a 13-fold increase in cell number, and partitioned loading of two types of cells compared with those under static conditions. As a proof of concept, HHSs with the loading cells show an enhanced regenerative capability in repair of the critical-sized segmental and osteoporotic bone defects in vivo. We expect that this post-bioprinting strategy can provide a universal, efficient, and promising way to promote cell-based regenerative therapy.

Exploratory Investigation of Zinc-Modified Borosilicate Bioactive Glass: A New Methodology for Its Biocompatibility, Immunoregulation, and Pro-Angiogenic Property Evaluation.

The assessment of biodegradable materials, such as bioactive glass, under the existing ISO 10993 standard test methods poses a significant challenge due to potential cell viability impairment caused by the accumulation of degraded products in a static environment. Therefore, innovative methodologies are urgently needed to tailor the unique biodegradation characteristics of these materials, providing more precise and scientific insights into biosafety and efficacy verification. Motivation by its bidirectional regulation of angiogenesis and immunity, zinc (Zn) was incorporated into sol-gel-derived borosilicate bioactive glasses (SBSGs) to fabricate Zn-incorporated borosilicate bioactive glasses (SBSG-Zn) to complement the tissue repair capabilities of bioactive glasses. Both SBSG and SBSG-Zn glasses consist of nanosized particles, slit mesoporous pores, high specific surface areas, and bioreactivity. In vitro comparative analysis, conducted according to ISO 10993 standards, demonstrates that only at suitable dilution rates─such as the 8-fold dilution employed in this study─do extracts of SBSG and SBSG-Zn glasses exhibit low cytotoxicity when cultured with human umbilical vein endothelial cells (HUVECs). Notably, SBSG-Zn glasses show optimal promotion of angiogenic gene expression in HUVECs. Furthermore, within an appropriate concentration range of released ions, SBSG-Zn glass extracts not only promote cell survival but also modulate the expression of anti-inflammatory genes while simultaneously inhibiting pro-inflammatory genes concurrently. After being implanted in rat subcutaneous defect models, both SBSG and SBSG-Zn glasses demonstrated the local immunoregulation and angiogenic effects. SBSG-Zn stands out by demonstrating superior modulation of M1/M2 polarization in macrophages as validated by altered secretion of key factors in macrophages and expression of relevant growth factors in HUVECs. These findings underscore the potential for convenient manipulation of localized angiogenic and immunoregulation through the incorporation of zinc into bioactive glass, emphasizing the importance of ensuring the appropriate ion doses are applied for achieving optimal therapeutic efficiency.

4D printed hydrogel scaffold with swelling-stiffening properties and programmable deformation for minimally invasive implantation.

The power of three-dimensional printing in designing personalized scaffolds with precise dimensions and properties is well-known. However, minimally invasive implantation of complex scaffolds is still challenging. Here, we develop amphiphilic dynamic thermoset polyurethanes catering for multi-material four-dimensional printing to fabricate supportive scaffolds with body temperature-triggered shape memory and water-triggered programmable deformation. Shape memory effect enables the two-dimensional printed pattern to be fixed into temporary one-dimensional shape, facilitating transcatheter delivery. Upon implantation, the body temperature triggers shape recovery of the one-dimensional shape to its original two-dimensional pattern. After swelling, the hydrated pattern undergoes programmable morphing into the desired three-dimensional structure because of swelling mismatch. The structure exhibits unusual soft-to-stiff transition due to the water-driven microphase separation formed between hydrophilic and hydrophobic chain segments. The integration of shape memory, programmable deformability, and swelling-stiffening properties makes the developed dynamic thermoset polyurethanes promising supportive void-filling scaffold materials for minimally invasive implantation.

Nanostructured conducting polymers as intelligent implant surface: fabricated on biomedical titanium with a potential-induced reversible switch in wettability.

Conducting polypyrrole (PPy) nanotube arrays, nanotube networks and irregular films are deposited on biomedical titanium. By in situ application of weak periodic potentials, the nanostructured conducting polymers undergo a reversible switch in wettability, which is a redox process of dopant molecules (as hydrophilic groups) immobilized and de-immobilized on the surface of the conducting polymers.

Magnesium-Organic Framework-Loaded Bisphosphonate-Functionalized Gel Scaffolds for Enhanced Bone Regeneration.

The development of magnesium-derived biomaterials is one of the most promising research in bone tissue engineering, and related strategies have been extensively used for tendon, skull, cartilage, and bone regeneration. Also, alendronate, a well-recognized drug for osteoporosis treatment, has recently attracted a great deal of attention for bone repair. However, rapid corrosion in vivo of Mg2+ and low systemic bioavailability of alendronate are the main limitations hampering their full exploitation. In this work, by means of physical and chemical cross-linking conjugating magnesium-metal-organic frameworks (Mg-MOFs) and bone-targeting alendronate to biocompatible gelatin scaffolds, a facile method is developed for the preparation of organic/inorganic nanocomposite gel scaffolds. The results affirmed that the nanocomposite gel scaffolds possessed excellent biocompatibility, continuous slow release of Mg2+ and alendronate, strong bone affinity, and bone regeneration. It is noteworthy that the continuous slow release of Mg2+ and alendronate could induce the macrophage switch to the M2 phenotype and promote osteogenic differentiation in the early stage, resulting in improved bone regeneration during implanting the scaffolds into the distal femoral. In summary, Mg-MOFs-loaded alendronate-modified gelatin gel scaffolds have been developed, exhibiting great potential for bone regenerative.

Application of piezoelectric materials in the field of bone: a bibliometric analysis.

In the past 4 decades, many articles have reported on the effects of the piezoelectric effect on bone formation and the research progress of piezoelectric biomaterials in orthopedics. The purpose of this study is to comprehensively evaluate all existing research and latest developments in the field of bone piezoelectricity, and to explore potential research directions in this area. To assess the overall trend in this field over the past 40 years, this study comprehensively collected literature reviews in this field using a literature retrieval program, applied bibliometric methods and visual analysis using CiteSpace and R language, and identified and investigated publications based on publication year (1984-2022), type of literature, language, country, institution, author, journal, keywords, and citation counts. The results show that the most productive countries in this field are China, the United States, and Italy. The journal with the most publications in the field of bone piezoelectricity is the International Journal of Oral & Maxillofacial Implants, followed by Implant Dentistry. The most productive authors are Lanceros-Méndez S, followed by Sohn D.S. Further research on the results obtained leads to the conclusion that the research direction of this field mainly includes piezoelectric surgery, piezoelectric bone tissue engineering scaffold, manufacturing artificial cochleae for hearing loss patients, among which the piezoelectric bone tissue engineering scaffold is the main research direction in this field. The piezoelectric materials involved in this direction mainly include polyhydroxybutyrate valerate, PVDF, and BaTiO3.

The effect of high temperature aging on the corrosion resistance, mechanical property and antibacterial activity of Cu-2205 DSS.

The effects of high temperature aging on the corrosion resistance, mechanical property and antibacterial activity of a copper-bearing 2205 duplex stainless steel (Cu-2205 DSS) were investigated. The results from scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and EDS analysis showed that after aging the proportion of γ phase in microstructure was increased and new σ phase and copper-rich precipitates were formed. The mechanical properties including hardness and tensile and yield strengths of the aged Cu-2205 DSS were significantly enhanced compared to the solution-treated Cu-2205 DSS as well as the 2205 DSS. Electrochemical measurements including electrochemical impedance spectroscopy, potentiodynamic polarization curves and potentiostatic polarization scan were performed to evaluate the corrosion behavior of the Cu-2205 DSS. It was found that aging increased the uniform corrosion resistance but had slightly adverse effect on the pitting corrosion resistance. Additionally, the antibacterial performance of aged Cu-2205 DSS was significantly improved compared to the solution treated Cu-2205 DSS, which was attributed to the more release of copper ions from the matrix that killed the bacteria cells and inhibited the biofilm formation on the surface. The above results suggest that Cu-2205 DSS after high temperature aging revealed good mechanical property, antibacterial performance, and corrosion resistance, which will further expand the application of duplex stainless steel in marine engineering fields.

NIR-Responsive TiO2 Biometasurfaces: Toward In Situ Photodynamic Antibacterial Therapy for Biomedical Implants.

Implant-related microbial infection is a challenging clinical problem, and its treatment requires efficient eradication of the biofilm from the implant surface. Near-infrared (NIR)-responsive strategies are proposed as an emerging efficient antibacterial therapy. However, the utilization of photosensitizers or photocatalytic/photothermal nanomaterials in the available approach likely induces high potential risks of interfacial deterioration and biosafety compromise. Herein, a TiO2 /TiO2- x metasurface with potent NIR-responsive antibacterial activity is produced on a Ti alloy implant by a newly invented topochemical conversion-based alkaline-acid bidirectional hydrothermal method (aaBH). Electromagnetic simulations prove that NIR absorption and near-field distribution of the metasurface can be tuned by the dimension and arrangement of the nanostructural unit. Promising antibacterial efficacy is proved by both in vitro and in vivo tests, with low-power NIR irradiation for 10 min. Besides, the designed nanostructure in the metasurface itself also shows excellence in enhancing the adhesion-related gene expression of human gingival fibroblasts that are exposed to 10 min of NIR irradiation, proving the potent nanostructure-induced biological effects. This work provides a biosafe and upscalable metasurfacing approach with extraordinary capacity of manipulating light adsorption, photocatalysis, and biological properties.

Biological Fixation of Bioactive Bone Cement in Vertebroplasty: The First Clinical Investigation of Borosilicate Glass (BSG) Reinforced PMMA Bone Cement.

PMMA bone cement has been clinically used for decades in vertebroplasty due to its high mechanical strength and satisfactory injectability. However, the interface between bone and PMMA is fragile and more prone to refracture in situ because PMMA lacks a proper biological response from the host bone with minimal bone integration and dense fibrous tissue formation. Here, we modified PMMA by incoporating borosilicate glass (BSG) with a dual glass network of [BO3] and [SiO4], which spontaneously modulates immunity and osteogenesis. In particular, the BSG modified PMMA bone cement (abbreviated as BSG/PMMA cement) provided an alkaline microenvironment that spontaneously balanced the activities between osteoclasts and osteoblasts. Furthermore, the trace elements released from the BSGs enhanced the osteogenesis to strengthen the interface between the host bone and the implant. This study shows the first clinical case after implantation of BSG/PMMA for three months using the dual-energy CT, which found apatite nucleation around PMMA instead of fibrous tissues, indicating the biological interface was formed. Therefore, BSG/PMMA is promising as a biomaterial in vertebroplasty, overcoming the drawback of PMMA by improving the biological response from the host bone.

Clay-based nanocomposite hydrogel with attractive mechanical properties and sustained bioactive ion release for bone defect repair.

Although clay-based nanocomposite hydrogels have been widely explored, their instability in hot water and saline solution inhibits their applications in biomedical engineering, and the exploration of clay-based nanocomposite hydrogels in bone defect repair is even less. In this work, we developed a stable clay-based nanocomposite hydrogel using 4-acryloylmorpholine as the monomer. After UV light illumination, the obtained poly(4-acryloylmorpholine) clay-based nanocomposite hydrogel (poly(4-acry)-clay nanocomposite hydrogel) exhibits excellent mechanical properties due to the hydrogen bond interactions between the poly(4-acryloylmorpholine) chains and the physical crosslinking effect of the nanoclay. Besides good biocompatibility, the sustainable release of intrinsic Mg2+ and Si4+ from the poly(4-acry)-clay nanocomposite hydrogel endows the system with excellent ability to promote the osteogenic differentiation of primary rat osteoblasts (ROBs) and can promote new bone formation effectively after implantation. We anticipate that these kinds of clay-based nanocomposite hydrogels with sustained release of bioactive ions will open a new avenue for the development of novel biomaterials for bone regeneration.

Interaction of storage medium and silver diamine fluoride on demineralized dentin.

OBJECTIVE: The effects of saliva on demineralized dentin and silver diamine fluoride (SDF) were investigated in vitro. METHODS: Dentin samples stored in deionized water (DIW), buffer solution (BS), basal medium mucin (BMM), and unstimulated whole saliva (UWS) were demineralized for 3 days and immersed in the same storage media. SDF as a 38 mass% solution was applied to the dentin samples for 3 minutes after they had been replaced in their respective medium. Surfaces were analyzed by scanning electron microscopy, energy-dispersive X-ray analysis (EDX), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). RESULTS: Scanning electron microscopy showed various surface deposits and coatings, including occlusion of dentinal tubules. DIW resulted in the thinnest coating, whereas BMM resulted in the thickest. EDX and XPS showed the formation of metallic silver and silver compounds in all four media, with the greatest formation in BS. XRD indicated that the main product was silver chloride except in DIW. Sulphur was found in BMM and UWS. EDX and XPS detected fluoride and XRD detected calcium fluoride and fluorohydroxyapatite in BS, BMM, and UWS. CONCLUSION: The interaction between SDF and demineralized dentin was dependent upon the storage medium. BMM provided an outcome most similar to human saliva.

Nanosurfacing Ti alloy by weak alkalinity-activated solid-state dewetting (AAD) and its biointerfacial enhancement effect.

Nanoscale manipulation of material surfaces can create extraordinary properties, holding great potential for modulating the implant-bio interface for enhanced performance. In this study, a green, simple and biocompatible nanosurfacing approach based on weak alkalinity-activated solid-state dewetting (AAD) was for the first time developed to nano-manipulate the Ti6Al4V surface by atomic self-rearrangement. AAD treatment generated quasi-periodic titanium oxide nanopimples with high surface energy. The nanopimple-like nanostructures enhanced the osteogenic activity of osteoblasts, facilitated M2 polarization of macrophages, and modulated the cross-talk between osteoblasts and macrophages, which collectively led to significant strengthening of in vivo bone-implant interfacial bonding. In addition, the titanium oxide nanopimples strongly adhered to the Ti alloy, showing resistance to tribocorrosion damage. The results suggest strong nano-bio interfacial effects, which was not seen for the control Ti alloy processed through traditional thermal oxidation. Compared to other nanostructuring strategies, the AAD technique shows great potential to integrate high-performance, functionality, practicality and scalability for surface modification of medical implants.

A more defective substrate leads to a less defective passive layer: Enhancing the mechanical strength, corrosion resistance and anti-inflammatory response of the low-modulus Ti-45Nb alloy by grain refinement.

Orthopedic and dental implants made of ß-type Ti alloys have low elastic modulus which can better relieve the stress shielding effects after surgical implantation. Nevertheless, clinical application of ß-type Ti alloys is hampered by the insufficient mechanical strength and gradual release of pro-inflammatory metallic ions under physiological conditions. In this study, the ß-type Ti-45Nb alloy is subjected to high-pressure torsion (HPT) processing to refine the grain size. After HPT processing, the tensile strength increases from 370 MPa to 658 MPa due to grain boundary strengthening and at the same time, the favorable elastic modulus is maintained at a low level of 61-72 GPa because the single ß-phase is preserved during grain refinement. More grain boundaries decrease the work function and facilitate the formation of thicker and less defective passive films leading to better corrosion resistance. In addition, more rapid repair of the passive layer mitigates release of metallic ions from the alloy and consequently, the inflammatory response is suppressed. The results reveal a strategy to simultaneously improve the mechanical and biological properties of metallic implant materials for orthopedics and dentistry. STATEMENT OF SIGNIFICANCE: The low modulus Ti-45Nb alloy is promising in addressing the complication of stress shielding induced by biomedical Ti-based materials with too-high elastic modulus. However, its insufficient strength hampers its clinical application, and traditional strengthening via heat treatments will compromise the low elastic modulus. In the current study, we enhanced the ultimate tensile strength of Ti-45Nb from 370 MPa to 658 MPa through grain-refinement strengthening, while the elastic modulus was maintained at a low value (61-72 GPa). Moreover, substrate grain-refinement has been proved to improve the corrosion resistance of Ti-45Nb with reduced inflammatory response both in vitro and in vivo. A relationship between the substrate microstructure and the surface passive layer has been established to explain the beneficial effects of substrate grain-refinement.

[Application and research status of bioactive glass in bone repair].

OBJECTIVE: To summarize the clinical application and research status of bioactive glass (BAG) in bone repair. METHODS: The recently published literature concerning BAG in bone repair at home and abroad was reviewed and summarized. RESULTS: BAG has been widely used in clinical bone repair with a favorable effectiveness. In the experimental aspect, to meet different clinical application needs, BAG has been prepared in different forms, such as particles, prosthetic coating, drug and biological factor delivery system, bone cement, and scaffold. And the significant progress has been made. CONCLUSION: BAG has been well studied in the field of bone repair due to its excellent bone repair performance, and it is expected to become a new generation of bone repair material.

A simultaneous grafting/vinyl polymerization process generates a polycationic surface for enhanced antibacterial activity of bacterial cellulose.

Bacterial cellulose (BC) is a biosynthesized carbohydrate polymer with excellent biocompatibility and water holding capability. However, it lacks an inherent antibacterial activity that has limited its in-depth biomedical applications. This study investigated a novel strategy of adopting a simultaneous process to chemically anchor a quaternary ammonium salt (R-N(CH3)+) with a special vinyl group (2-methacryloyloxyethyl trimethylammonium chloride, METAC) onto the BC, and meanwhile, enhance the density of (R-N(CH3)+) via free radical vinyl polymerization. The results have confirmed the transition of BC surface from a negatively-charged surface to a polycationic surface via such a simultaneous reaction. As compared to chitin film (a representative of R-NH3+), the resulting METAC-grafted BC (a representative of high-density R- N(CH3)+) acquired excellent water absorbability (40 times of dry weight of the BC), 99% antibacterial activity against Escherichia coli and Staphylococcus aureus, a satisfactory in-vitro biocompatibility, and a better in-vivo wound healing outcome with an excellent in-vivo antibacterial efficacy. This study has exhibited potential in utilizing a facile method to prepare a bio-safe, adaptive antibacterial surface for various biomedical applications.