SE-VisionTransformer: Hybrid Network for Diagnosing Sugarcane Leaf Diseases Based on Attention Mechanism.

Sugarcane is an important raw material for sugar and chemical production. However, in recent years, various sugarcane diseases have emerged, severely impacting the national economy. To address the issue of identifying diseases in sugarcane leaf sections, this paper proposes the SE-VIT hybrid network. Unlike traditional methods that directly use models for classification, this paper compares threshold, K-means, and support vector machine (SVM) algorithms for extracting leaf lesions from images. Due to SVM's ability to accurately segment these lesions, it is ultimately selected for the task. The paper introduces the SE attention module into ResNet-18 (CNN), enhancing the learning of inter-channel weights. After the pooling layer, multi-head self-attention (MHSA) is incorporated. Finally, with the inclusion of 2D relative positional encoding, the accuracy is improved by 5.1%, precision by 3.23%, and recall by 5.17%. The SE-VIT hybrid network model achieves an accuracy of 97.26% on the PlantVillage dataset. Additionally, when compared to four existing classical neural network models, SE-VIT demonstrates significantly higher accuracy and precision, reaching 89.57% accuracy. Therefore, the method proposed in this paper can provide technical support for intelligent management of sugarcane plantations and offer insights for addressing plant diseases with limited datasets.

Vascular Derived ECM Improves Therapeutic Index of BMP-2 and Drives Vascularized Bone Regeneration.

Vascularized osteogenesis is essential for successful bone regeneration, yet its realization during large size bone defect healing remains challenging due to the difficulty to couple multiple biological processes. Herein, harnessing the intrinsic angiogenic potential of vascular derived extracellular matrix (vECM) and its specific affinity to growth factors, a vECM/GelMA based hybrid hydrogel delivery system is constructed to achieve optimized bone morphogenetic protein-2 (BMP-2) therapeutic index and provide intrinsic angiogenic induction during bone healing. The incorporation of vECM not only effectively regulates BMP-2 kinetics to match the bone healing timeframe, but also promotes angiogenesis both in vitro and in vivo. In vivo results also show that vECM-mediated BMP-2 release remarkably enhances vascularized bone formation for critical size bone defects. In particular, blood vessel ingrowth stained with CD31 marker in the defect area is substantially encouraged over the course of healing, suggesting incorporation of vECM served roles in both angiogenesis and osteogenesis. Thus, the authors' study exemplifies that affinity of growth factor towards ECM may be a promising strategy to be leveraged to develop sophisticated delivery systems endowed with desirable properties for regenerative medicine applications.

Remotely Temporal Scheduled Macrophage Phenotypic Transition Enables Optimized Immunomodulatory Bone Regeneration.

Precise timing of macrophage polarization plays a pivotal role in immunomodulation of tissue regeneration, yet most studies mainly focus on M2 macrophages for their anti-inflammatory and regenerative effects while the essential proinflammatory role of the M1 phenotype on the early inflammation stage is largely underestimated. Herein, a superparamagnetic hydrogel capable of timely controlling macrophage polarization is constructed by grafting superparamagnetic nanoparticles on collagen nanofibers. The magnetic responsive hydrogel network enables efficient polarization of encapsulated macrophage to the M2 phenotype through the podosome/Rho/ROCK mechanical pathway in response to static magnetic field (MF) as needed. Taking advantage of remote accessibility of magnetic field together with the superparamagnetic hydrogels, a temporal engineered M1 to M2 transition course preserving the essential role of M1 at the early stage of tissue healing, as well as enhancing the prohealing effect of M2 at the middle/late stages is established via delayed MF switch. Such precise timing of macrophage polarization matching the regenerative process of injured tissue eventually leads to optimized immunomodulatory bone healing in vivo. Overall, this study offers a remotely time-scheduled approach for macrophage polarization, which enables precise manipulation of inflammation progression during tissue healing.

Iodine Immobilized Metal-Organic Framework for NIR-Triggered Antibacterial Therapy on Orthopedic Implants.

Iodine has been known as an effective disinfectant with broad-spectrum antimicrobial potency yet without drug resistance risk when used in clinic. However, the exploration of iodine for antibacterial therapy in orthopedics remains sparse due to its volatile nature and poor solubility. Herein, leveraging the superior absorption capability of metal-organic frameworks (MOFs) and their inherent photocatalytic properties, iodine-loaded MOF surface is presented to realize responsive iodine release along with intracellular reactive oxygen species(ROS) oxidation under near-infrared (NIR) exposure to achieve synergistic antibacterial effect. Iodine is successfully loaded using vapor deposition process onto zeolitic imidazolate framework-8(ZIF-8), which is immobilized onto micro arc oxidized titanium via a hydrothermal approach. The combination of NIR-triggered iodine release and ZIF-8 mediated ROS oxidative stress substantially augments the antibacterial efficacy of this approach both in vitro and in vivo. Furthermore, this composite coating also supported osteogenic differentiation of bone marrow stromal cells, as well as improved osseointegration of coated implants using an intramedullary rat model, suggesting improvement of antibacterial efficacy does not impair osteogenic potential of the implants. Altogether, immobilization of iodine via MOF on orthopedic implants with synergistic antibacterial effect can be a promising strategy to combat bacterial infections.

Spatiotemporal regulation of angiogenesis/osteogenesis emulating natural bone healing cascade for vascularized bone formation.

Engineering approaches for growth factor delivery have been considerably advanced for tissue regeneration, yet most of them fail to provide a complex combination of signals emulating a natural healing cascade, which substantially limits their clinical successes. Herein, we aimed to emulate the natural bone healing cascades by coupling the processes of angiogenesis and osteogenesis with a hybrid dual growth factor delivery system to achieve vascularized bone formation. Basic fibroblast growth factor (bFGF) was loaded into methacrylate gelatin (GelMA) to mimic angiogenic signalling during the inflammation and soft callus phases of the bone healing process, while bone morphogenetic protein-2 (BMP-2) was bound onto mineral coated microparticles (MCM) to mimics osteogenic signalling in the hard callus and bone remodelling phases. An Initial high concentration of bFGF accompanied by a sustainable release of BMP-2 and inorganic ions was realized to orchestrate well-coupled osteogenic and angiogenic effects for bone regeneration. In vitro experiments indicated that the hybrid hydrogel markedly enhanced the formation of vasculature in human umbilical vein endothelial cells (HUVECs), as well as the osteogenic differentiation of mesenchymal stem cells (BMSCs). In vivo results confirmed the optimal osteogenic performance of our F/G-B/M hydrogel, which was primarily attributed to the FGF-induced vascularization. This research presents a facile and potent alternative for treating bone defects by emulating natural cascades of bone healing.

Metabolomics reveals the effect of valproic acid on MCF-7 and MDA-MB-231 cells.

1. Breast cancer is one of the most common malignancies in women worldwide. Metabolomics has been shown to be a promising strategy to elucidate the underlying pathogenesis of cancer and identify new targets for cancer diagnosis and therapy. Valproic acid (VPA), a histone deacetylase inhibitor, is a potential new drug in tumor therapy. This work used metabolomics to examine the effect of VPA on metabolism in breast cancer cells.2. Based on UPLC-MS/MS, we identified 3137 differential metabolites in human breast cancer MCF-7 cells and 2472 differential metabolites in human breast cancer MDA-MB-231 cells after VPA treatment.3. We selected 63 differential metabolites from MCF-7 samples and 61 differential metabolites from MDA-MB-231 cells with the more conspicuous changing trend. Furfural was up-regulated after VPA treatment in both cell lines. In both samples, VPA exerted an effect on the beta-alanine metabolism pathway and the taurine and hypotaurine metabolism pathway.4. This study identified the effect of VPA on metabolites and metabolic pathways in breast cancer cells, and these findings may contribute to the identification of new targets for breast cancer treatment.

Bone combined cement grafting in giant cell tumor around the knee reduces mechanical failure.

OBJECTIVES: The aims of our study are (1) to explore the risk factors of mechanical failure (MF), (2) to figure out an index to evaluate this risk, and (3) to select an optimal reconstruction strategy to reduce this risk. METHODS: We retrospectively reviewed 104 patients from Dec. 2008 to Mar. 2016, undergone extensive knee curettages in our institution. Radiographs and post-operative interviews were used to classified cases of MF. Relative factors (age, tumor location, the invaded area, etc.) were also collected and analyzed by SPSS software. RESULTS: Thick subchondral bony layer (p = 0.006) and combined grafting of the cement and bone (p = 0.006) had lower risk of mechanical failure. Mechanical failure appeared to happen in the femur (p = 0.012) more easily. The ROC curve (AUC = 0.722) reveals that less post-operative bony layer (≤ 3.3 mm) is more likely to cause mechanical failure. The Kaplan-Meier survival curve showing increased survival in those patients after a combination grafting surgery (HR, 3.799; p = 0.006). CONCLUSION: Based on our study results, combined grafting of the cement and bone reduced the risk of mechanical failure in the knee due to the thin subchondral bone layer (SCB), especially in the femur.

Coordination-dependent surface strain and rational construction of robust structures.

A surface relaxation model is established to study the elastic properties of nanoscale structures. This model predicts coordination-dependent strain at the surface and thickness-dependent stiffness of a material. Several atomic layers at the surface endure a significant strain gradient, which is dominated by the intrinsic properties of the material. The stiffness of low-dimensional materials is enhanced by surface relaxation effect. Surface effects on strong structures, including honeycomb structure and octet-truss structure with a high stiffness-to-weight ratio, are discussed. For these structures assembled with nanobeams, the Young's modulus decreases with decreasing size of the struts. The coupling between Young's modulus and relative density can be scaled down by engineering tensile strain on the struts.

Succession of bacterial microbiota in tilapia fillets at 4 °C and in situ investigation of spoilers.

The succession of bacterial microbiota in tilapia fillets during cold storage at 4 °C was investigated employing PCR-DGGE method. Results showed that Pseudomonas was the most dominant genus during entire storage period. Shewanella and Psychrobacter were also always present, but became dominant only after 3 days of storage. Acinetobacter, Brevibacterium, Flavobacterium, Dietzia and Janthinobacterium were always the minor genera, among which Acinetobacter and Brevibacterium disappeared 6 days later, and Dietzia and Janthinobacterium only appeared at the end of storage. Further, the potential spoiler(s) of tilapia fillets at 4 °C were investigated in situ. The spoilage ability of a specific group of bacteria was evaluated as follows: Certain preservatives were selectively added to fillets to inhibit a specific group of bacteria, and then the changes in spoilage degree of fillets were determined. In this way the spoilage ability of the inhibited bacteria was evaluated. Our experiments showed that protamine strongly inhibited Pseudomonas but rarely inhibited Psychrobacter, Acinetobacter and Brevibacterium, but garlic juice, on the contrary, strongly inhibited the latter three but rarely inhibited the former. The mixed preservative, which consisted of protamine and garlic juice, didn't play better than protamine alone in preventing the spoilage of fillets. This indicated that Psychrobacter, Acinetobacter and Brevibacterium contribute little to the spoilage of tilapia fillets.

Size- and dimensionality-dependent optical, magnetic and magneto-optical properties of binary europium-based nanocrystals: EuX (X = O, S, Se, Te).

Europium chalcogenides (EuX, X = O, S, Se, Te), a class of prototypical Heisenberg magnetic semiconductors, exhibit intriguing properties in optics, magnetism, and magneto-optics at the nanoscale, and have broad application potential in optical/magnetic sensors, spintronics, optical isolators, etc. EuX nanocrystals (NCs) exhibit enhanced properties, such as high saturation magnetization, a strong magneto-optic effect (Faraday rotation), and high magneto resistance, which are all unanimously dependent on the NC's size, shape, and surface information. In this report, we give an overview of the fundamental properties of bulk EuX, and illustrate the quantum confinement effects on the optical, magnetic and magneto-optical properties of EuX nanostructures. We then focus on doping and self-assembly-two efficient methods that enhance magnetic properties by manipulating magnetic coupling in EuX nanostructures. In particular, we look towards future research on Eu(2+) NCs, which along with the overview provides an up-to-date platform for evaluating the fundamental properties and application potential of Eu-based semiconductors.

The antipsychotic drug pimozide promotes apoptosis through the RAF/ERK pathway and enhances autophagy in breast cancer cells.

The antipsychotic drug pimozide has been demonstrated to inhibit cancer. However, the precise anti-cancer mechanism of pimozide remains unclear. The purpose of this study was to investigate the effects of pimozide on human MCF-7 and MDA-MB-231 breast cancer cell lines, and the potential involvement in the RAF/ERK signaling. The effects of pimozide on cells were examined by 4,5-dimethylthiazol-2-yl-3,5-diphenylformazan, wound healing, colony formation, transwell assays, and caspase activity assay. Flow cytometry and acridine orange and ethidium bromide staining were performed to assess changes in cells. Transmission electron microscopy and monodansylcadaverine staining were used to observe autophagosomes. The cyclic adenosine monophosphate was evaluated using the FRET system. Immunohistochemistry, immunofluorescence, RNA interference, and western blot investigated the expression of proteins. Mechanistically, we focus on the RAF1/ERK signaling. We detected pimozide was docked to RAF1 by Schrodinger software. Pimozide down-regulated the phosphorylation of RAF1, ERK 1/2, Bcl-2, and Bcl-xl, up-regulated Bax, and cleaved caspase-9 to induce apoptosis. Pimozide might promote autophagy by up-regulating cAMP. The enhancement of autophagy increased the conversion of LC3-I to LC3-II and down-regulated p62 expression. But mTOR signaling was not involved in promoting autophagy. The knockdown of RAF1 expression induced autophagy and apoptosis in breast cancer cells, consistent with the results of pimozide or sorafenib alone. Blocked autophagy by chloroquine resulted in the impairment of pimozide-induced apoptosis. These data showed that pimozide inhibits breast cancer by regulating the RAF/ERK signaling pathway and might activate cAMP-induced autophagy to promote apoptosis and it may be a potential drug for breast cancer treatment.

Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy.

Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including low drug loading efficiency, premature drug leakage, and poor cellular internalization. Herein, we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy. This self-assembled micelle possesses the following essential components for CPT: (1) pH-sensitive PEG (OHC-PEG-CHO) for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles, which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake; (2) polypeptide polylysine-polyphenylalanine (PKF) synthesized via ring-opening polymerization for micelle formation and CPT analogue loading; (3) dimeric CPT (DCPT) with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites. Interestingly, the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles. Also, the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation. In conclusion, this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.

Co-delivery of dimeric camptothecin and chlorin e6 via polypeptide-based micelles for chemo-photodynamic synergistic therapy.

BACKGROUND: The integration of photodynamic therapy with a chemical drug-delivery system has displayed great potential in enhancing anticancer therapy. However, the solubility and non-specific biodistribution of both chemotherapeutic agents and photosensitizers continue to pose challenges that hinder their clinical applications. METHOD: A polypeptide-based nanoscale drug delivery system was fabricated to address the prementioned issues. An amphiphilic polymer was formed by conjugating the photosensitizer chlorin e6 (Ce6) onto a polypeptide poly-(L-lysine)-b-polyphenylalanine (PKF) for encapsulating the model drug dimeric camptothecin (DCPT), and the nanoparticles (PCD) with high drug loading efficiency were further modified with acid-sensitive polyethylene glycol (PEG) to yield the drug delivery sytem (PPCD). RESULTS: The DCPT and Ce6 encapsulation efficiency were analyzed as 99% and 73.5%, respectively. In phosphate-buffered saline (PBS) solution at a pH of 7.4, the PEG shell improved the stability of micelles and shielded their positive charge while in the acidic tumor microenvironment, the pH-sensitive PEG layer was removed to expose the cationic nanoparticles, thus facilitating the cellular uptake of PPCD micelles. Benefiting from the enhanced cellular internalization, the amount of intracellular reactive oxygen species (ROS) treated with PCD and PPCD micelles were obviously increased. Furthermore, the enhanced anti-cancer efficacy prompted by PPCD micelles was validated through cellular and animal study. CONCLUSION: This study presents a promising method to promote the solubility and biodistribution of both chemotherapeutic agent and photosensitizer, thereby facilitating the further application of chemo-photodynamic cancer therapy.

Reversing the imbalance in bone homeostasis via sustained release of SIRT-1 agonist to promote bone healing under osteoporotic condition.

The imbalance of bone homeostasis is the root cause of osteoporosis. However current therapeutic approaches mainly focus on either anabolic or catabolic pathways, which often fail to turn the imbalanced bone metabolism around. Herein we reported that a SIRT-1 agonist mediated molecular therapeutic strategy to reverse the imbalance in bone homeostasis by simultaneously regulating osteogenesis and osteoclastogenesis via locally sustained release of SRT2104 from mineral coated acellular matrix microparticles. Immobilization of SRT2104 on mineral coating (MAM/SRT) harnessing their electrostatic interactions resulted in sustained release of SIRT-1 agonist for over 30 days. MAM/SRT not only enhanced osteogenic differentiation and mineralization, but also attenuated the formation and function of excessive osteoclasts via integrating multiple vital upstream signals (ß-catenin, FoxOs, Runx2, NFATc1, etc.) in vitro. Osteoporosis animal model also validated that it accelerated osteoporotic bone healing and improved osseointegration of the surrounding bone. Overall, our work proposes a promising strategy to treat osteoporotic bone defects by reversing the imbalance in bone homeostasis using designated small molecule drug delivery systems.

A Comparative Study of Three Nucleic Acid Integrity Assay Systems.

Background: The measurement of nucleic acid quality, especially the analysis of integrity, is a key step for many downstream experiments in biomedical research and quality control of biomaterials. General gel electrophoresis is a traditional method for nucleic acid integrity analysis. Currently, more electrophoresis techniques are becoming standardized and automated operations with higher precision. In this study, we have evaluated the comparability and bias of the outcomes from three commercial assay systems. Methods: Seventy-two deoxyribonucleic acid (DNA) and 67 ribonucleic acid (RNA) samples were selected for methodological comparison among different systems. The DNA Quality Number (DQN) and RNA Quality Number (RQN) of BIOptic Qsep400, DNA Quality Score (DQS) and RNA Quality Score (RQS) of PerkinElmer Labchip GX Touch HT were separately compared with the DNA Integrity Number (DIN) and RNA Integrity Number (RINe) of the Agilent 4200 TapeStation according to Clinical and Laboratory Standards Institute (CLSI) guideline (EP09-A3). Results: The biases of the mean estimated between DQN and DIN, DQS and DIN both exceeded the acceptance criteria. The Passing-Bablok regression analysis between DQN and DIN, and the Deming regression analysis between DQS and DIN, showed the biases were both within the acceptance criteria, and the bias between DQN and DIN was smaller. For the comparisons of RQN and RINe, RQS and RINe, the regression analyses revealed the biases were both within the acceptance criteria. The bias of the mean estimated between RQS and RINe was outside of the acceptance criteria. Conclusions: There was a good comparability in nucleic acid integrity detection between BIOptic Qsep400 and PerkinElmer Labchip GX Touch HT with the Agilent 4200 TapeStation. However, the bias and linear correlations require more attention between systems.

PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner.

Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-ß (PDGFR-ß) pathway is conventionally considered as an important pathway to promote osteogenesis; however, recent study suggested its role during osteogenesis to be controversial. Regarding the differential functions of this pathway during 3 stages of bone healing, we hypothesized that temporal inhibition of PDGF-BB/PDGFR-ß pathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells, toward osteogenic lineage, which leads to improved bone regeneration. We first validated that inhibition of PDGFR-ß at late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts. This effect was also replicated in vivo by showing accelerated bone formation when block PDGFR-ß pathway at late stage of critical bone defect healing mediated using biomaterials. Further, we found that such PDGFR-ß inhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally. Mechanistically, timely inhibition of PDGFR-ß blocked extracellular regulated protein kinase 1/2 pathway, which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis. This study offered updated understanding of the use of PDGFR-ß pathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.

Pimozide inhibits the growth of breast cancer cells by alleviating the Warburg effect through the P53 signaling pathway.

The Warburg effect is a promising target for the diagnosis and treatment of cancer, referring to the ability of cancer cells to generate energy through high levels of glycolysis even in the presence of oxygen, allowing them to grow and proliferate rapidly. The antipsychotic Pimozide has strong anti-breast cancer effects both in vivo and in vitro, whether Pimozide has an inhibitory effect on aerobic glycolysis has not been elucidated. In this study, Pimozide inhibited the Warburg effect of breast cancer cells by hindering glucose uptake, ATP level and lactate production; reducing the extracellular acidification rate (ECAR); suppressing the expression of PKM2, a rate-limiting enzyme in glycolysis. Intriguingly, Pimozide was significantly involved in reprogramming glucose metabolism in breast cancer cells through a p53-dependent manner. Mechanistic studies demonstrated Pimozide increased the expression of p53 through inhibition of the PI3K/Akt/MDM2 signaling pathway, which in turn downregulated the expression of PKM2. In sum, our results suggest that Pimozide mediates the p53 signaling pathway through PI3K/AKT/MDM2 to inhibit the Warburg effect and breast cancer growth, and it may be a potential aerobic glycolysis inhibitor for the treatment of breast cancer.

Remote Eradication of Bacteria on Orthopedic Implants via Delayed Delivery of Polycaprolactone Stabilized Polyvinylpyrrolidone Iodine.

Bacteria-associated late infection of the orthopedic devices would further lead to the failure of the implantation. However, present ordinary antimicrobial strategies usually deal with early infection but fail to combat the late infection of the implants due to the burst release of the antibiotics. Thus, to fabricate long-term antimicrobial (early antibacterial, late antibacterial) orthopedic implants is essential to address this issue. Herein, we developed a sophisticated MAO-I2-PCLx coating system incorporating an underlying iodine layer and an upper layer of polycaprolactone (PCL)-controlled coating, which could effectively eradicate the late bacterial infection throughout the implantation. Firstly, micro-arc oxidation was used to form a microarray tubular structure on the surface of the implants, laying the foundation for iodine loading and PCL bonding. Secondly, electrophoresis was applied to load iodine in the tubular structure as an efficient bactericidal agent. Finally, the surface-bonded PCL coating acts as a controller to regulate the release of iodine. The hybrid coatings displayed great stability and control release capacity. Excellent antibacterial ability was validated at 30 days post-implantation via in vitro experiments and in vivo rat osteomyelitis model. Expectedly, it can become a promising bench-to-bedside strategy for current infection challenges in the orthopedic field.

A trilogy antimicrobial strategy for multiple infections of orthopedic implants throughout their life cycle.

Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles. However, ordinary antimicrobial treatments usually failed to combat multiple waves of infections during arthroplasty and prosthesis revisions etc. As these incidents could easily introduce new microbial pathogens in/onto the implants. Herein, we demonstrate that an antimicrobial trilogy strategy incorporating a sophisticated multilayered coating system leveraging multiple ion exchange mechanisms and fine nanotopography tuning, could effectively eradicate bacterial infection at various stages of implantation. Early stage bacteriostatic effect was realized via nano-topological structure of top mineral coating. Antibacterial effect at intermediate stage was mediated by sustained release of zinc ions from doped CaP coating. Strong antibacterial potency was validated at 4 weeks post implantation via an implanted model in vivo. Finally, the underlying zinc titanate fiber network enabled a long-term contact and release effect of residual zinc, which maintained a strong antibacterial ability against both Staphylococcus aureus and Escherichia coli even after the removal of top layer coating. Moreover, sustained release of Sr2+ and Zn2+ during CaP coating degradation substantially promoted implant osseointegration even under an infectious environment by showing more peri-implant new bone formation and substantially improved bone-implant bonding strength.

An orthobiologics-free strategy for synergistic photocatalytic antibacterial and osseointegration.

Tissue damage caused by hyperthermia during photothermal therapy (PTT) has largely limited its clinical applications for implant infection. However, rescue of tissue regeneration by conjugating orthobiologics with PTT has been problematic as they can easily deactivate biologics while eradicating bacteria. Herein, we report an orthobiologics-free strategy to synergistically couple photocatalytic antibacterial with pro-osteogenic capacity via self-assembly of copper sulphide nanoparticle (CuS NP) and reduced graphene oxide (rGO) on implant surface. This strategy not only offers enhanced photothermal effects for bacterial eradiation via near-infrared light (NIR), but also promotes vascularized osseointegration via cooperation of copper ion with rGO. In vitro and in vivo data showed that coupling CuS and rGO synergistically increased antibacterial efficacy of implants by 40 times and successfully destroyed bacterial biofilm upon NIR. Moreover, CuS/rGO decorated surface substantially improved bone marrow stromal cell adhesion, proliferation, as well as subsequent differentiation toward osteoblast. We also revealed that enhanced peri-implant vascularization may be attributed to the sustained release of copper ion from CuS NPs, which further collaborated with rGO to promote vascularized osseointegration. Altogether, this novel orthobiologics-free approach offers a practical alternative to circumvent the intrinsic drawbacks of PTT and endows powerful antibacterial and pro-osteogenic capacities for implant associated infections.