Re-tear after arthroscopic rotator cuff repair can be predicted using deep learning algorithm.

The application of artificial intelligence technology in the medical field has become increasingly prevalent, yet there remains significant room for exploration in its deep implementation. Within the field of orthopedics, which integrates closely with AI due to its extensive data requirements, rotator cuff injuries are a commonly encountered condition in joint motion. One of the most severe complications following rotator cuff repair surgery is the recurrence of tears, which has a significant impact on both patients and healthcare professionals. To address this issue, we utilized the innovative EV-GCN algorithm to train a predictive model. We collected medical records of 1,631 patients who underwent rotator cuff repair surgery at a single center over a span of 5 years. In the end, our model successfully predicted postoperative re-tear before the surgery using 62 preoperative variables with an accuracy of 96.93%, and achieved an accuracy of 79.55% on an independent external dataset of 518 cases from other centers. This model outperforms human doctors in predicting outcomes with high accuracy. Through this methodology and research, our aim is to utilize preoperative prediction models to assist in making informed medical decisions during and after surgery, leading to improved treatment effectiveness. This research method and strategy can be applied to other medical fields, and the research findings can assist in making healthcare decisions.

Nano selenium-doped TiO2 nanotube arrays on orthopedic implants for suppressing osteosarcoma growth.

Osteosarcoma, the most common primary malignant bone tumor, is characterized by malignant cells producing osteoid or immature bone tissue. Most osteosarcoma patients require reconstructive surgery to restore the functional and structural integrity of the injured bone. Metal orthopedic implants are commonly used to restore the limb integrity in postoperative patients. However, conventional metal implants with a bioinert surface cannot inhibit the growth of any remaining cancer cells, resulting in a higher risk of cancer recurrence. Herein, we fabricate a selenium-doped TiO2 nanotube array (Se-doped TNA) film to modify the surface of medical pure titanium substrate, and evaluate the anti-tumor effect and biocompatibility of Se-doped TNA film. Moreover, we further explore the anti-tumor potential mechanism of Se-doped TNA film by studying the behaviors of human osteosarcoma cells in vitro. We provide a new pathway for achieving the anti-tumor function of orthopedic implants while keeping the biocompatibility, aiming to suppress the recurrence of osteosarcoma.

Iodine-Doped 3D Print Ti Alloy for Antibacterial Therapy on Orthopedic Implants.

This study presents a novel approach to mitigating bacterial infections and antibiotic resistance in medical implants through the integration of iodine-doping and 3D printing techniques. Iodine, with its potent antibacterial properties, and titanium alloy (Ti), a popular metal for implants due to its mechanical and biological properties, were combined via electrodeposition on 3D-printed titanium alloy (3D-Ti) implants. Scanning electron microscopy, energy dispersive spectroscopy, and X-ray photoelectron spectroscopy confirmed the successful creation of iodine-doped titanium implants with improved iodine content due to the rough surface of the 3D-printed material. In vitro studies revealed that these implants significantly inhibited bacterial adhesion and biofilm formation and showed favorable release kinetics for iodine ions. Biocompatibility tests demonstrated no cytotoxic effects and good hemocompatibility. The implants demonstrated enhanced antimicrobial efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria strains. The findings imply that the integration of iodine-doping and 3D printing technologies is a promising strategy for treating postoperative infections associated with medical implants, consequently bettering the prognosis for patients. Future investigations are encouraged to delve into the long-standing impacts and prospective clinical utility of this groundbreaking methodology.

Homogeneous silver nanoparticle loaded polydopamine/polyethyleneimine-coated bacterial cellulose nanofibers for wound dressing.

Utilizing mussel-inspired chemistry is an advanced strategy for surface modification, because dopamine (DA) can form a material-independent adhesive coating and further functionalization can be achieved, including the production of silver nanoparticles (AgNPs). Nevertheless, DA easily aggregates in the nanofiber network structure of bacterial cellulose (BC), which not only blocks the pores in the BC structure but also leads to the formation of large silver particles and the burst release of highly cytotoxic silver ions. Herein, a homogeneous AgNP-loaded polydopamine (PDA)/polyethyleneimine (PEI) coated BC was constructed via a Michael reaction between PDA and PEI. Under the action of PEI, the PDA/PEI coating was uniformly attached to the BC fiber surface with a thickness of approximately 4 nm, and homogeneous AgNPs were produced on the uniform PDA/PEI/BC (PPBC) fiber surface. The sustained release of silver ions was better from AgNPs@PPBC than from AgNPs@PDA/BC. The obtained AgNPs@PPBC exhibited excellent antibacterial activities and cytocompatibility. The results of the in vivo assay indicated that the AgNPs@PPBC dressing could inhibit S. aureus infection and inflammation, promote hair follicle growth, enhance collagen deposition, and accelerate wound healing within 12 days compared with BC. These results illustrate that the homogeneous AgNPs@PPBC dressing has great potential for treating infected wounds.

Polymer bilayer-Micro arc oxidation surface coating on pure magnesium for bone implantation.

Background: Pure magnesium-based ortho-implants have a number of advantages. However, vital parameters like degradation rate and biocompatibility still call for significant improvement. Methods: In this study, poly (1,3-trimethylene carbonate) (PTMC) and polydopamine (PDA) bilayer and micro arc oxidation composite coatings were prepared successively on magnesium surface by immersion method and microarc oxidation. Its corrosion resistance and biocompatibility were evaluated by in vitro corrosion tests, cellular compatibility experiments, and in vivo animal experiments. Results: In vitro experiments demonstrated that the composite coating provides excellent corrosion protection and biocompatibility. Animal studies demonstrated that the composite coating slowed the degradation of the implant and was not toxic to animal viscera. Conclusion: In conclusion, the inorganic-organic composite coating proposed in this study provided good corrosion resistance and enhanced biocompatibility for pure magnesium implants. The translational potential of this article: The translational potential of this article is to develop an anti-corrosion composite coating on a pure magnesium surface and to verify the viability of its use in animal models. It is hoped to open up a new approach to the design of new degradable orthopedic magnesium-based implants.

Arthroscopic Superior Capsule Reconstruction With Combined Fascia Lata Autograft and Synthetic Scaffold Patch Graft for the Treatment of Irreparable Rotator Cuff Tears Yields Favorable Clinical and Radiographic Outcomes at Minimum 2-Year Follow-Up.

PURPOSE: To report the results of the arthroscopic superior capsule reconstruction (ASCR) technique with a combined fascia lata autograft and synthetic scaffold patch graft for irreparable massive rotator cuff tears (RCTs). METHODS: The period for this retrospective study was between December 2016 and December 2020. The criteria for inclusion were patients treated arthroscopically for an incompletely repaired massive RCT (dimension >5 cm and 2 tendons fully torn, intact or reparable subscapularis tendons and teres minor tendon with or without irreparable infraspinatus, a radiological Hamada classification between grade 0 and 4, and a minimum 24-month postoperative follow-up). Clinical outcomes were evaluated preoperatively and at a final follow-up by a visual analog scale (VAS) for pain and range of motion along with the American Shoulder and Elbow Surgeons score (ASES), the University of California Los Angeles score (UCLA), and the Constant-Murley score (CMS). Radiological outcomes were assessed, according to the rotator cuff arthropathy (RCA) and the acromiohumeral distance (AHD) stages. Graft integrity and muscle fatty infiltration were evaluated by magnetic resonance imaging (MRI). RESULTS: A total of 43 patients were enrolled in the study with a mean follow-up duration of 45.6 months (range: 24 to 64). All clinical scores also improved at the 2-year follow-up (mean: VAS 0.7 [SD 0.7] vs 5.4 [SD 1.1]; P < .001; mean: ASES 92.6 [SD 8.0] vs 34.8 [SD 13.4]; P < .001; mean UCLA 31.5 [SD 3.9] vs 11.0 [SD 3.2]; P < .001; and mean CMS 86.6 [SD 7.2] vs 40.0 [SD 11.6]; P < .001), and 39 of 43 fascia lata grafts were fully intact on MRI (91%). CONCLUSIONS: ASCR with a combined fascia lata autograft and synthetic scaffold patch graft resulted in good functional outcomes, with a high rate of graft healing at the 2-year follow-up. All patients achieved clinically relevant improvement (met minimal clinically important differences [MCID]) on ASES, UCLA, and VAS with improved abduction strength restoration. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Enhanced efficiency of calcium-derived oleoyl serine on osteoporosis via Wnt/ß-catenin pathway.

Osteoporosis is a common disease of the elderly that affects millions of patients worldwide. It is mainly characterized by low bone mineral density and increased risk of fracture due to the deterioration of the bone structure, leading to difficulties in functional recovery, reduced quality of life, increased disability risk and mortality in the population. It has already been a major public health problem. Osteoporosis is a chronic disease that is difficult to treat in the elderly population, so it is crucial to develop new drugs for the treatment of osteoporosis. Oleoyl serine, an endogenous fatty acyl amide found in bone, has been shown to have excellent anti-osteoporosis effects, but it is easily hydrolyzed by amidases in vivo. The aim of this study is to determine the anti-osteoporotic effect of calcium-derived oleoyl serine, a novel oleoyl serine derivative and the molecular mechanism underneath. In vitro experiments demonstrated that calcium-derived oleoyl serine suppressed the expression of Fabp4, and Cebpα while Alp, and Runx2 was significantly upregulated compared with the oleoyl serine group and control. With the activation of ß-catenin, calcium-derived oleoyl serine restored the abnormal osteogenesis and lipogenesis, indicating calcium-derived oleoyl serine compared with oleoyl serine has better effects on promoting osteogenesis and suppressing lipogenesis. In vivo experiment agreed with these findings that calcium-derived oleoyl serine promotes osteogenesis and suppresses its lipogenesis to ameliorate osteoporosis via a ß-catenin dependent method. It is a new candidate for treating osteoporosis.

A study of the growth mechanism of large-diameter double-wall TiO2 nanotube arrays fabricated by high voltage anodization.

Background: Research on the growth mechanism of titanium dioxide (TiO2) nanotube arrays fabricated by anodic oxidation is essential to achieve artificial control of the microstructure and to expand their applications. In our previous work, we reported the preparation of highly ordered large-diameter double-wall TiO2 nanotube arrays prepared by high voltage anodization. Methods: In this paper, we observed and analyzed the initial growth process of large-diameter double-wall TiO2 nanotube arrays anodized at 120 V in ethylene glycol electrolyte containing aluminum fluoride (NH4F) and water (H2O), such as the evolution of surface and cross-sectional morphologies, the influence of current density on growth rate, the transition process from nanoholes to nanotubes, and the evolution of dimples on the remaining substrate. Results: On the basis of our observations and inspirations from the existing viewpoints, we established growth models of large-diameter double-wall TiO2 nanotube arrays corresponding to different growth stages to explain the growth process. The growth rate of anodic oxide film changes accordingly with the current density. The compact anodic oxide film formed initially actually contains outer layer and inner layer, with no obvious interface between them. Then, the bottom even levels of the inner layer and outer layer bulge towards the substrate and become individual hemisphere-like structures. The inner layer becomes the outer wall, and the outer layer becomes inner wall. Eventually, V-shaped large-diameter and double-wall TiO2 nanotube arrays form. Conclusions: The results presented in this work are significant and provide a better understanding of the growth mechanism of large-diameter double-wall TiO2 nanotube arrays anodized by high voltage.

Rotator cuff repair with biodegradable high-purity magnesium suture anchor in sheep model.

Background: Rotator cuff tear has become one of the diseases affecting people's living quality. Conventional anchor materials such as titanium alloy and poly-lactic acid can lead to postoperative complications like bone defects and aseptic inflammation. Magnesium (Mg)-based implants are biodegradable and biocompatible, with strong potential to be applied in orthopaedics. Methods: In this study, we developed a high-purity (HP) Mg suture anchor and studied its mechanical properties and degradation behavior in vitro. Furthermore, we described the use of high-purity Mg to prepare suture anchor for the rotator cuff repair in sheep. Results: The in vitro tests showed that HP Mg suture anchor possess proper degradation behavior and appropriate mechanical property. Animal experiment indicated that HP Mg suture anchor provided reliable anchoring function in 12 weeks and showed no toxic effect on animal organs. Conclusion: In summary, the HP Mg anchor presented in this study had favorable mechanical property and biosecurity.The translational potential of this article: The translational potential of this article is to use high-purity Mg to develop a degradable suture anchor and verify the feasibility of the application in animal model. This study provides a basis for further research on the clinical application of biodegradable high-purity Mg suture anchor.

Current development of bovine jugular vein conduit for right ventricular outflow tract reconstruction.

Right ventricular outflow tract (RVOT) reconstruction is a common surgical method to treat congenital cardiac lesions, and bovine jugular vein conduit (BJVC) has become a prevalent candidate of prosthetic material for this procedure since 1999. Although many clinical studies have shown encouraging results on BJVCs, complications such as stenosis, aneurysmal dilatation, valve insufficiency, and infective endocarditis revealed in other clinical outcomes still remain problematic. This review describes the underlying mechanisms causing respective complications, and summarizes the current technological development that may address those causative factors. Novel crosslinking agents, decellularization techniques, conduit coatings, and physical reinforcement materials have improved the performances of BJVCs. The authors expect that the breakthroughs in the clinical application of BJVC may come from new genetic research findings and advanced characterization apparatuses and bioreactors, and are optimistic that the BJVC will in the future provide sophisticated therapies for next-generation RVOT reconstruction.

Meta-Analysis of Knee Joint Function Recovery after Anterior Cruciate Ligament Reconstruction by Accelerated Rehabilitation Surgery.

Objective: This investigation was undertaken to systematically assess the impact of increasingly rapid recovery treatment on the functional status of the knee following anterior cruciate ligament restructuring. Methods: Computer search from the establishment of the database to March 2022 in China Knowledge Network Database (CNKI), PubMed, EMBASE, ScienceDirect, CochraneLibrary, China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM). The control group was given only traditional rehabilitation training, and the observation group was treated with perioperative accelerated rehabilitation surgery intervention randomized controlled trial (RCT). Data for all included studies were extracted by two independent researchers, and the risk of bias for the quality of each included study was assessed by the Cochrane Handbook 5.1.0 criteria. Meta-analysis of the collected data by using RevMan5.4 statistical software. Results: A total of 593 articles were retrieved from the computer database and 8 RCT articles with a total of 636 samples were finally included for meta-analysis. According to the Jadad scale, the RCT score of 8 articles was ≥4 points. Meta-analysis was performed on the postoperative VAS scores of the ERAS group and the traditional rehabilitation group, and the heterogeneity test showed Chi2 = 288.60, df = 5, P < 0.00001, and I 2 = 99%. There was a statistically significant difference in the postoperative VAS scale between the intervention and the traditional rehabilitation model (P < 0.05). Eight articles reported the effect of accelerated rehabilitation surgery on the recovery of knee joint motion after ACL rehabilitation. After meta-analysis, the heterogeneity test showed Chi2 = 314.98, df = 7, P < 0.00001, and I 2 = 98%, and it can be concluded from the analysis that, compared with the traditional rehabilitation model, the enhanced rehabilitation surgery has an effect on the joint function after anterior cruciate ligament reconstruction. The improvement effect was more significant, and the difference was statistically significant (P < 0.05). Four articles reported the effect of enhanced recovery after surgery intervention on the range of motion of the knee joint of patients, the heterogeneity test showed Chi2 = 117.52, df = 2, P < 0.00001, and I 2 = 98%, through analysis, and compared with the traditional rehabilitation model and the enhanced recovery. The effect of surgery on the range of motion of the knee joint after ACL reconstruction was more significant, and the difference was statistically significant (P < 0.05). The effect of enhanced recovery after surgery and traditional rehabilitation mode on the incidence of postoperative adverse reactions in patients undergoing ACL reoperation was analyzed. The results of heterogeneity test showed that Chi2 = 1.59, df = 2, P=0.66 > 0.05, and I 2 = 98%, and the analysis showed that, compared with the traditional rehabilitation mode, enhanced rehabilitation surgery can significantly reduce the risk of adverse reactions after anterior cruciate ligament reconstruction (P < 0.05). An inverted funnel plot was used to analyze publication bias in studies with quality of life as an outcome measure. The results showed that Egger's test P=0.0005 < 0.001 suggesting that there may be a certain degree of publication bias. Conclusion: The existing research evidence shows that accelerating the reconstruction of anterior cruciate ligament can effectively promote the recovery of knee joint function, reduce the pain of patients, and reduce postoperative complications. However, more research is needed to further verify this.

Identification and analysis of a selective DYRK1A inhibitor.

The dysregulation of DYRK1A is implicated in many diseases such as cancer, diabetes, and neurodegenerative diseases. Alzheimer's disease is one of the most common neurodegenerative disease and has elevated interest in DYRK1A research. Overexpression of DYRK1A has been linked to the formation of tau aggregates. Currently, an effective therapeutic treatment that targets DYRK1A is lacking. A specific small-molecule inhibitor would further our understanding of the physiological role of DYRK1A in neurodegenerative diseases and could be presented as a possible therapeutic option. In this study, we identified pharmacological interactions within the DYRK1A active site and performed a structure-based virtual screening approach to identify a selective small-molecule inhibitor. Several compounds were selected in silico for enzymatic and cellular assays, yielding a novel inhibitor. A structure-activity relationship analysis was performed to identify areas of interactions for the compounds selected in this study. When tested in vitro, reduction of DYRK1A dependent phosphorylation of tau was observed for active compounds. The active compounds also improved tau turbidity, suggesting that these compounds could alleviate aberrant tau aggregation. Testing the active compound against a panel of kinases across the kinome revealed greater selectivity towards DYRK1A. Our study demonstrates a serviceable protocol that identified a novel and selective DYRK1A inhibitor with potential for further study in tau-related pathologies.

Aberrant Expression of miR-100 in Plasma of Patients with Osteoporosis and its Potential Diagnostic Value.

BACKGROUND: Osteoporosis is one of the most commonly diagnosed age-related bone diseases worldwide, and it is also one of the leading causes of fracture. MicroRNAs (miRNAs) are critical molecular regulators that are involved in the bone re-modelling processes, and the circulating miRNAs were stable in the peripheral blood. Thus, to detect the level of miRNAs in plasma of osteoporotic patients may be an efficient, repeatable, and inexpensive method for the early diagnosis and evaluation of the therapeutic efficacy of osteoporosis. The aim of the present study was to investigate the potential diagnostic value of miR-100 in plasma of patients with osteoporosis. METHODS: A total of 120 osteoporotic patients were recruited and 120 healthy individuals were also included as the control group. The plasma of the participants was collected and the RNAs were extracted. The expressions of miR-100 in different clinical samples were examined using the RT-qPCR method. Furthermore, receiver operating characteristics curve (ROC) was drawn to determine the diagnostic value of miR-100 for osteoporosis. Next, the correlation between the plasma levels of miR-100 and T-scores of the patients were evaluated and, finally, the correlation between the plasma level of miR-100 and the expression levels of 25OH-D2 and 25OH-D3 were analyzed. RESULTS: miR-100 was significantly increased in plasma of patients with osteoporosis in comparison with healthy individuals; moreover, results of ROC analysis indicated that plasma level of miR-100 is a sensitive biomarker that could distinguish osteoporosis patients from healthy controls (AUC, 0.8916, 95% confidence interval (CI), 0.8468 to 0.9364). Furthermore, miR-100 was found to be negatively correlated with both vBMD (r = -0.3117, p = 0.0005) and Lumbar Spine L2-L4 T-score in patients with osteoporosis (r = -0.2929, p = 0.012). Finally, the plasma level of miR-100 was negatively correlated with the levels of 25OH-D2 (r = -0.3002, p = 0.0008) and 25OH-D3 (r = -0.3105, p = 0.0006) of the osteoporotic patients. CONCLUSIONS: miR-100 was abnormally increased in the plasma of osteoporotic patients, suggesting that circulating miR-100 could serve as potential biomarker for the diagnosis and treatment osteoporosis.

Surface properties and bioactivity of TiO2 nanotube array prepared by two-step anodic oxidation for biomedical applications.

A highly ordered TiO2 nanotube array has been prepared on a commercial pure titanium substrate in a hydrofluoric (HF) electrolyte using a DC power source through two-step anodic oxidation. The morphology, composition, wettability and surface energy of the nanotube array have been characterized by using a field-emission scanning electron microscope (FE-SEM), a transmission electron microscope (JEM-2010) with energy-dispersive X-ray spectrometer EDX (INCA OXFORD), X-ray diffraction method, an atomic force microscope (AFM), an optical contact angle measuring device and the Owens method with two liquids. The electrochemical behaviours of anodic oxidation films with different structures have been investigated in Sodium Lactate Ringer's Injection at 37±1°C by potentiodynamic polarization curve and electrochemical impedance spectroscopy. The formation mechanism of the nanotube array and the advantages of two-step oxidation have been discussed according to the experimental observation and the characterized results. Meanwhile, the structural changes of nanotubes are analysed according to the results of impedance spectroscopy. Cytotoxicity testing and cell adhesion and proliferation have been studied in order to evaluate the bioactivity of the nanotube array film. The diameters of nanotubes are in the range of 120-140 nm. The nanotube surface shows better wettability and higher surface energy compared to the bare substrate. The nanotube surface exhibits a wide passivation range and good corrosion resistance. The growth of the nanotube array is the result of the combined action of the anodization and field-assisted dissolution. The nanotube array by two-step oxidation becomes more regular and orderly. Moreover, the nanotube array surface is non-toxic and favourable to cell adhesion and proliferation. Such nanotube array films are expected to have significant biomedical applications.

Nanofibers grafted on titanium alloy: the effects of fiber alignment and density on osteoblast mineralization.

The surface of medical implant alloy Ti-6Al-4V was chemically modified to allow it to covalently bond with collagen/PVA nanofibers. These nanofibers were successfully attached to the Ti-6Al-4V surface in three different morphologies: randomly oriented high-density fiber, COL(H); randomly oriented low-density fiber, COL(L); and aligned high-density fiber, COL(A). The effects of the morphology of these covalently-bound collagen nanofibers on the growth and differentiation of osteoblasts were studied for 21 days. The low-density nanofibers covered approximately 80% of the Ti64 surface, while the high-density nanofibers covered nearly 100%. These covalently attached fibrous coatings remained attached to the metal surface after 3 weeks of cell culture. In the first week the aligned fibers of COL(A) allowed the osteoblasts to stretch and elongate in the direction of the fibers. This directional elongation was not seen in the cells on the randomly-oriented samples. Cells proliferated and differentiated on all three surfaces over time. By the end of the test, the amount of type I collagen secreted by the cells on COL(H) was the highest, while the degree of mineralization was highest on COL(A) among the three samples (p < 0.05). Different nanofiber morphologies changed the cell morphology and the secretion of cellular products. The mechanisms remained to be investigated. The surface of medical implant alloy Ti-6Al-4V was chemically modified to allow it to covalently bond with collagen/PVA nanofibers. The SEM micrographs in the top row show the random and aligned morphology of the collagen-PVA nanofibers. The nanofibers on COL(A) were aligned in the general direction indicated by the arrow. The second row are images from EDX titanium element mapping. The location of the titanium elements are shown as bright dots. The low-density nanofibers, COL(L), covered approximately 80% of the Ti64 surface, while the high-density nanofibers, COL(H) and COL(A), covered nearly 100%. All three surfaces demonstrated good biocompatibility for the cultured osteoblasts. The fiber alignment seemed to have an effect on early cellular morphology (day 7), collagen secretion and calcium deposition, while the density of the fibers seemed to have no significant effect on cell behavior. SEM micrographs of osteoblasts after 7 and 14 days of cell culture are shown in the third and fourth rows. The surface of COL(L) has more cell-free spots indicated by (*) on day 7 as other two surfaces were covered by cells. The nanofibers could no longer be observed and were covered with mineralized granules (circles) after 14 days of cell culture. The cells appear stretched out on the mineralized granules.

Osteosarcoma cells promote the production of pro-tumor cytokines in mesenchymal stem cells by inhibiting their osteogenic differentiation through the TGF-ß/Smad2/3 pathway.

Mesenchymal stem cells (MSCs) are among the most important components of the osteosarcoma microenvironment and are reported to promote tumor progression. However, the means by which osteosarcoma cells modulate MSC behavior remains unclear. The aim of this study was to determine the effects of osteosarcoma cells on both the production of pro-tumor cytokines by mesenchymal stem cells (MSCs) and the osteogenic differentiation of MSCs. High level of transforming growth factor-ß (TGF-ß) was detected in three osteosarcoma cell lines. Conditioned media (CM) from the osteosarcoma cell lines Saos-2 and U2-OS were used to stimulate the cultured MSCs. We found that osteosarcoma cells promoted the production of IL-6 and VEGF in MSCs by inhibiting their osteogenic differentiation. Furthermore, TGF-ß in tumor CM was proved to be an important factor. The TGF-ß neutralizing antibody antagonized the effects induced by osteosarcoma CM. The inhibition of Smad2/3 by siRNA significantly decreased the production of IL-6 and VEGF in MSCs and induced their osteogenic differentiation. We also found that Smad2/3 enhanced the expression of ß-catenin in MSCs by decreasing the level of Dickkopf-1 (DKK1). Although the inhibition of ß-catenin did not affect the production of IL-6 or VEGF, or the gene expression of the early osteogenic markers Runx2 and ALP, it did enhance the gene expression of osteocalcin. Taken together, our data indicate that osteosarcoma cells secrete TGF-ß to maintain the stemness of MSCs and promote the production of pro-tumor cytokines by these cells.

Dual effects and mechanism of TiO2 nanotube arrays in reducing bacterial colonization and enhancing C3H10T1/2 cell adhesion.

Competition occurs between the osteoblasts in regional microenvironments and pathogens introduced during surgery, on the surface of bone implants, such as joint prostheses. The aim of this study was to modulate bacterial and osteoblast adhesion on implant surfaces by using a nanotube array. Titanium oxide (TiO2) nanotube arrays, 30 nm or 80 nm in diameter, were prepared by a two-step anodization on titanium substrates. Mechanically polished and acid-etched titanium samples were also prepared to serve as control groups. The standard strains of Staphylococcus epidermidis (S. epidermidis, American Type Culture Collection [ATCC]35984) and mouse C3H10T1/2 cell lines with osteogenic potential were used to evaluate the different responses to the nanotube arrays, in bacteria and eukaryotic cells. We found that the initial adhesion and colonization of S. epidermidis on the surface of the TiO2 nanotube arrays were significantly reduced and that the adhesion of C3H10T1/2 cells on the surface of the TiO2 nanotube arrays was significantly enhanced when compared with the control samples. Based on a surface analysis of all four groups, we observed increased surface roughness, decreased water contact angles, and an enhanced concentration of oxygen and fluorine atoms on the TiO2 nanotube surface. We conclude that the TiO2 nanotube surface can reduce bacterial colonization and enhance C3H10T1/2 cell adhesion; multiple physical and chemical properties of the TiO2 nanotube surface may contribute to these dual effects.

Biotemplated syntheses of macroporous materials for bone tissue engineering scaffolds and experiments in vitro and vivo.

The macroporous materials were prepared from the transformation of cuttlebone as biotemplates under hydrothermal reactions and characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric/differential thermal analyses (TG-DTA), and scanning electron microscopy (SEM). Cell experimental results showed that the prepared materials as bone tissue engineering scaffolds or fillers had fine biocompatibility suitable for adhesion and proliferation of the hMSCs (human marrow mesenchymal stem cells). Histological analyses were carried out by implanting the scaffolds into a rabbit femur, where the bioresorption, degradation, and biological activity of the scaffolds were observed in the animal body. The prepared scaffolds kept the original three-dimensional frameworks with the ordered porous structures, which made for blood circulation, nutrition supply, and the cells implantation. The biotemplated syntheses could provide a new effective approach to prepare the bone tissue engineering scaffold materials.

The use of quaternised chitosan-loaded PMMA to inhibit biofilm formation and downregulate the virulence-associated gene expression of antibiotic-resistant staphylococcus.

Biomaterial-associated infections remain a serious complication in orthopaedic surgery. Treatments, including the local use of antibiotic-loaded polymethylmethacrylate (PMMA) bone cement, are not always successful because of multiantibiotic-resistant organisms. In this study, we synthesised a new quaternised chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) that contains a series of substitutions of quaternary ammonium and demonstrated that HACC with a 26% degree of substitution (DS; referred to as 26%HACC) had a strong antibacterial activity and simultaneously good biocompatibility with osteogenic cells. We loaded 26%HACC at 20% by weight into PMMA bone cement to investigate whether HACC in PMMA prevents bacterial biofilm formation on the surface of bone cements. Chitosan-loaded PMMA (at the same weight ratio), gentamicin-loaded PMMA and PMMA with no antibiotic were also investigated and compared. Two clinical isolates, Staphylococcus epidermidis 389 and methicillin-resistant S. epidermidis (MRSE287), and two standard strains, S. epidermidis (ATCC35984) and methicillin-resistant Staphylococcus aureus (ATCC43300), were selected to evaluate the bacterial biofilm formation at 6, 12 and 24 h using the spread plate method, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The results showed that 26%HACC-loaded PMMA inhibited biofilm formation on its surface, while the PMMA control and chitosan-loaded PMMA were unable to inhibit biofilm formation. The gentamicin-loaded PMMA decreased the number of viable methicillin-resistant Staphylococcus strains, but its ability to inhibit biofilm formation was lower than 26%HACC-loaded PMMA. Real-time PCR demonstrated that 26%HACC-loaded PMMA markedly downregulated the expression of icaAD, which encodes essential enzymes for polysaccharide intercellular adhesion (PIA) biosynthesis, upregulated the expression level of icaR, which negatively mediates icaAD expression, and also downregulated the expression of MecA, which encodes membrane-bound enzymes known to be penicillin-binding proteins. Our study indicates that 26%HACC-loaded PMMA prevents biofilm formation of Staphylococcus, including antibiotic-resistant strains, on the surface of bone cement, and downregulates the virulence-associated gene expression of antibiotic-resistant staphylococcus, thus providing a promising new strategy for combating implant infections and osteomyelitis.

[Application of enriched bone marrow compound with fibrin glue in repairing old radial bone defect in rabbits].

OBJECTIVE: To explore the feasibility of using enriched bone marrow (BM) compound with fibrin glue (FG) in repairing old radial bone defect. METHODS: Totally 36 New Zealand rabbits were equally randomized into three groups: simple FG group, BM+FG group, and enriched BM+FG group. A 1.5-cm segmental bone defect was made at the left radial in each animal. After one month, the defect was implanted with the engineered bone. Before implantation, a compound of enriched BM with FG underwent electron microscopy, long-term culture, and bacteriological culture. Four, 8, and 12 weeks after operations, the osteogenetic effect was evaluated using X-ray observation, HE staining, or Van Gieson staining, and a semi-quantitative analysis was performed. RESULTS: Electron microscopy showed enriched BM were compatible well with FG. No bacterial contamination or oncogenicity was observed after long-term culture. X-ray showed the repair effectiveness was significantly higher in BM+FG group and enriched BM+FG group than in simple FG group. Eight and 12 weeks after surgery, the Yang scores were significantly higher in enriched BM+FG group than in BM+FG group [(9.348±0.364évs.(7.984±0.229éìF=40.167ìP=0.001; (12.664±0.388)vs. (10.584±0.836é, F=20.3647ìP=0.004]. In addition, the Yang's scores at bone defects in BM+FG group and enriched BM+FG group were higher at the 12(th) week than in the 8(th) week. (F=36.004ìP=0.001; F=155.141ìP=0.000; respectively)The bone defects were repaired at varied degrees were histologically observed in BM+FG group and enriched BM+FG group during the observations. CONCLUSION: Implantation of BM+FG or enriched BM+FG are effective in repairing old radial bone defects, while simple FG shows not such effect.