Sprayable Berberine-Silk Fibroin Microspheres with Extracellular Matrix Anchoring Function Accelerate Infected Wound Healing through Antibacterial and Anti-inflammatory Effects.

The conventional method of applying local medications for treating wound infections is often ineffective because of the dilution of drugs by the excess wound exudate. In addition, there have been insufficient studies investigating the adhesion between drug-loaded nanomaterials and cells or tissue. To address this intractable problem, berberine-silk fibroin microspheres (Ber@MPs) with an extracellular matrix-anchoring function were developed in this study. The microspheres were prepared from silk fibroin using the polyethylene glycol emulsion precipitation method. Subsequently, berberine was loaded onto the microspheres. Our results revealed that Ber@MPs firmly anchored to cells, continuously releasing berberine in the microenvironment. Moreover, both Ber@MPs and Ber@MPs-cell complexes exerted a strong and long-lasting antibacterial effect against Staphylococcus aureus and Staphylococcus epidermidis in the microenvironment, despite the large amount of wound exudate. In addition, Ber@MPs effectively resisted the inflammatory response induced by lipopolysaccharides and accelerated the migration of fibroblasts and neovascularization of endothelial cells cultured in inflammation-induced media. Finally, the in vivo experiments confirmed that the Ber@MP spray accelerated the healing of infected wounds via its antibacterial and anti-inflammatory effects. Therefore, this study provides a novel strategy for treating infected wounds in the presence of excess exudate.

Regulation of Chondrocyte Differentiation by miR-455-3p Secreted by Bone Marrow Stem Cells through Phosphatase and Tensin Homolog Deleted on Chromosome Ten/Phosphoinositide 3-Kinase-Protein Kinase B.

The effects of the regulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) by microribonucleic acid- (miR-) 455-3p on bone marrow stem cells' (BMSCs') chondrogenic development were examined based on the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signal pathway. The alterations in miR-455-3p and PTEN were identified using osteoarthritis (OA) and healthy chondrocytes. Rats raised on the SD diet had their BMSCs isolated for chondrocyte-induced differentiation (blank group), transfected miR-455-3p mimic (mimic group), and inhibitor (inhibitor group). Besides, cell proliferation, alizarin red mineralization staining, and the activity of alkaline phosphatase (ALP) were detected. Real-time fluorescent quantitation polymerase chain reaction (PCR) and Western blot were utilized to detect Runx2, OPN, OSX, COL2A1 mRNA, and the difference between PI3K and AKT. Dual-luciferase reporter (DLR) genes were selected to analyze the target relationship of miR-455-3p to PTEN. It was demonstrated that miR-455-3p in OA was downregulated, while PTEN was upregulated (P < 0.05) in comparison to healthy chondrocytes (P < 0.05). Versus those in the blank group, alizarin red mineralization staining and the activity of ALP increased; RUNX, OPN, OSX, COL2A1 mRNA, p-PI3K, and p-AKT were elevated in the mimic group (P < 0.05). Versus those in the blank and mimic groups, alizarin red mineralization staining and the activity of ALP reduced; RUNX, OPN, OSX, COL2A1 mRNA, p-PI3K, and p-AKT were downregulated in the inhibitor group (P < 0.05). miR-455-3p could target PTEN to inhibit its expression, thus activating the PI3K/AKT signal pathway and promoting BMSCs chondrocyte-induced differentiation. The research results provided reference for the occurrence of OA and the study on therapeutic target.

Withdrawn: Ticagrelor reduces myocardial cell injury induced by myocardial ischemia/reperfusion in diabetic rats by activating JAK2/STAT3.

The above article from Cell Biology International, published online on 5 December 2022, on Wiley Online Library (https://doi.org/10.1002/cbin.11940), has been withdrawn by agreement between the journal Editor in Chief, Sergio Schenkman, and John Wiley and Sons Ltd. The withdrawal has been agreed due to a technical error at the publisher that caused the article to be mistakenly published online although it had been rejected due to evidence that the peer review process for this paper was manipulated.

Lipoprotein (a) variability is associated with mean follow-up C-reactive protein in patients with coronary artery disease following percutaneous coronary intervention.

BACKGROUND: Increased lipoprotein (a) [lp (a)] has proinflammatory effects, which increase the risk of coronary artery disease. However, the association between lp (a) variability and follow-up C-reactive protein (CRP) level in patients undergoing percutaneous coronary intervention (PCI) has not been investigated. AIM: To explore the association between lp (a) variability and mean CRP levels within the 1st year post-PCI. METHODS: Results of lp (a) and CRP measurements from at least three follow-up visits of patients who had received PCI were retrospectively analyzed. Standard deviation (SD), coefficient of variation (CV), and variability independent of the mean (VIM) are presented for the variability for lp (a) and linear regression analysis was conducted to correlate lp (a) variability and mean follow-up CRP level. The relationship of lp (a) variability and inflammation status was analyzed by restricted cubic spline analysis. Finally, exploratory analysis was performed to test the consistency of results in different populations. RESULTS: A total of 2712 patients were enrolled. Patients with higher variability of lp (a) had a higher level of mean follow-up CRP (P < 0.001). lp (a) variability was positively correlated with the mean follow-up CRP (SD: ß = 0.023, P < 0.001; CV: ß = 0.929, P < 0.001; VIM: ß = 1.648, P < 0.001) by multivariable linear regression analysis. Exploratory analysis showed that the positive association remained consistent in most subpopulations. CONCLUSION: Lp (a) variability correlated with mean follow-up CRP level and high variability could be considered an independent risk factor for increased post-PCI CRP level.

Icariin-loaded sulfonated polyetheretherketone with osteogenesis promotion and osteoclastogenesis inhibition properties via immunomodulation for advanced osseointegration.

Preventing prosthesis loosening due to insufficient osseointegration is critical for patients with osteoporosis. Endowing implants with immunomodulatory function can effectively enhance osseointegration. In this work, we loaded icariin (ICA) onto 3D porous sulfonated PEEK (SPEEK) via polydopamine (PDA) modification. Modified ICA-PDA@SPEEK not only promoted the polarization of macrophages to the anti-inflammatory M2 type, but also enhanced the osteogenesis of bone mesenchymal stem cells (BMSCs) and inhibited RANKL-induced osteoclastogenesis by regulating cytokine from macrophages. In vivo experiments further showed that ICA-PDA@SPEEK regulated the host immune response and promoted osseointegration in ovariectomized (OVX) rats. The above results demonstrated that ICA-PDA@SPEEK could be an excellent orthopedic biomaterial with immunomodulatory properties.

Optimizing the strontium content to achieve an ideal osseointegration through balancing apatite-forming ability and osteogenic activity.

Implant failure caused by unsatisfying osseointegration is still a noteworthy clinical problem. Strontium (Sr) has been confirmed to be a bioactive element that facilitates bone growth. In this study, Sr was surface incorporated in titanium (Ti) implant with different contents. The XRD results demonstrated that Sr existed mainly in the form of SrTiO3. All Sr-contained implants showed sustainable Sr2+ release behavior. Meanwhile, the Sr2+ release rate was proportional to the Sr content. The in vitro immersing test showed that the apatite-forming ability on the implant surface was decreased with the increase of Sr content. Conversely, the cell experiments manifested that implants with high content of Sr were more favorable to cell spreading, proliferation, osteogenic differentiation, and extracellular matrix mineralization. The in vivo implant experiment revealed that Sr-incorporation could improve osseointegration, new bone formation and mineralization, and bone-implant bonding strength. In addition, Ti5Sr, which possessed a combined good osteogenic activity and apatite-forming ability, exhibited the best in vivo overall performance. In summary, we first put forward the competitive effect of osteogenic activity and apatite-forming ability on bone-implant osseointegration, which would provide a new strategy for implant design.

Macrophage-biomimetic porous Se@SiO2 nanocomposites for dual modal immunotherapy against inflammatory osteolysis.

BACKGROUND: Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (porous Se@SiO2 nanospheres) to manage inflammatory osteolysis. RESULTS: Macrophage membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments. CONCLUSION: Our findings suggest that M-Se@SiO2 have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty.

Antibacterial application of gentamicin-silk protein coating with smart release function on titanium, polyethylene, and Al2O3 materials.

Peri-implant infection after hip and knee arthroplasty is a common and serious complication. Titanium (Ti), polyethylene (PE), and Al2O3 materials used as joint prosthesis materials have good biocompatibility and mechanical strength but no antibacterial effect. This study aimed to provide a theoretical basis for the design and manufacture of joint prosthesis materials with antibacterial effect. We applied a coating of gentamicin-silk protein (GS-Silk) on the surface of these materials. We characterized the Ti, PE, and Al2O3 materials coated with GS-Silk (experimental group) and performed in vivo and in vitro experiments to test antibacterial activity. Scanning electron microscopy confirmed successful GS-Silk coating, and infrared spectroscopy confirmed successful loading of gentamicin onto the three materials. Nanoscratch test proved that the GS-Silk coating is relatively reliable on the surface of these three materials. The antibacterial effect of the coating in vitro and in vivo was verified by performing bacteriostatic ring test in vitro, bacterial adhesion test, and subendothelial implant infection test. We demonstrated that GS-Silk coating can effectively load gentamicin onto Ti, PE, and Al2O3 materials and change the gentamicin release rate with a change in the solution pH to achieve intelligent release. The GS-Silk coating is relatively reliable on the surface of these three materials. Ti, PE, and Al2O3 materials coated with GS-Silk have good antibacterial ability, both in vivo and in vitro.

MicroRNA-16-5p Inhibits Osteoclastogenesis in Giant Cell Tumor of Bone.

Giant cell tumor (GCT) of bone is an aggressive skeletal tumor characterized by localized bone resorption. MicroRNA-16-5p (miR-16-5p) has been reported to be downregulated in lesions of patients with GCT, but little is known about its role in GCT. To explore the underlying function of miR-16-5p in GCT, we first detected its expression in patients with GCT. The results showed that osteoclast formation increased, whereas miR-16-5p expression considerably decreased with the severity of bone destruction. Furthermore, we found that miR-16-5p expression considerably decreased with the progression of receptor activator of nuclear factor-κB ligand- (RANKL-) induced osteoclastogenesis. Functionally, miR-16-5p mimics significantly reduced RANKL-induced osteoclast formation. However, treatment with an inhibitor of miR-16-5p significantly promoted osteoclastogenesis. These findings reveal that miR-16-5p inhibits osteoclastogenesis and that it may represent a therapeutic target for giant cell tumor of bone.