Journal of Biomaterials Science, Polymer Edition最新文献

Osteoarthritis (OA) is a chronic disease that causes pain, morbidity, and disability. The main strategy for OA treatment focuses on inflammation suppression, inhibition of osteoclastogenesis, and protection of articular cartilage. These functions cannot be performed effectively by monotherapy. Therefore, an effective drug delivery system is required, capable of containing and controlling the efflux of various drugs to alleviate osteoclastogenesis, protect cartilage and subchondral bone, and suppress inflammation. In this work, an encapsulation system is constructed using a self-healing chitosan hydrogel and allocated compound drugs. The self-healing gel is composed of branched-functionalized chitosan, created by simultaneously using polycaprolactone polyethylene glycol azide as a block polymer and the host-guest assembly of β-cyclodextrin and adamantane. Inhibitors of the NFkB pathway are loaded into the cavities of β-cyclodextrin and the spring-like structure of the block polymer, which can be rapidly released upon joint friction (due to the reassembly of β-cyclodextrin and adamantane by shear stress and the stretch of the block polymer). In vitro experiments using BMMs and the ATDC5 cell line confirm that the developed hydrogel can simultaneously suppress osteoclastogenesis and induce chondrogenesis. Additionally, a model of knee arthritis in C57 mice was used to confirm that this double-crosslinked encapsulation system can lubricate the knee joint surface and provide adequate protection on demand through shear-responsive drug release.

Docetaxel (Doc), as a first-line chemotherapy drug for prostate cancer (PC), often loses its therapeutic efficacy due to acquired resistance and lack of targeting specificity. Therefore, there is a need to develop a novel drug that can overcome Doc resistance and enhance its targeting ability to inhibit PC progression. In this study, we prepared Au/Doc/Quer@PDA/A10-3.2 nanoparticles (NPs) composite drug by encapsulating Doc and quercetin (Quer) within polydopamine (PDA)-coated Au NPs and further modifying them with RNA oligonucleotide aptamer A10-3.2. A10-3.2 was used for specific targeting of prostate-specific membrane antigen (PSMA)-positive PC cells (LNCaP). Quer was employed to reverse the resistance of Doc-resistant cell line (LNCaP/R) to Doc. Physical characterization using ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR) confirmed the successful preparation of Au/Doc/Quer@PDA/A10-3.2 NPs. Fluorescence imaging and flow cytometry experiments demonstrated the targeting ability of Au/Doc/Quer@PDA/A10-3.2 NPs towards PSMA-positive LNCaP/R cells. Cell proliferation, apoptosis, invasion, and migration experiments revealed that Quer reversed the resistance of LNCaP/R cells to Doc. Immunoblotting experiments further confirmed the mechanism behind sensitization of chemotherapy by Quer. Finally, we evaluated the therapeutic efficacy of Au/Doc/Quer@PDA/A10-3.2 NPs in a mouse model of PC. In conclusion, this study synthesized and validated a novel nano-composite drug (Au/Doc/Quer@PDA/A10-3.2 NPs) for combating Doc-resistant PC, which could potentially be applied in clinical treatment of PC.

Periodontitis is a common chronic inflammatory disease primarily caused by the prevalence of bacterial overgrowth resulting in the development of an inflammatory condition that destroys the tooth's supporting tissues and eventual tooth loss. Comparatively, to other treatment methods, it is difficult for topical antibacterial drugs to effectively permeate the biofilm's physical barrier, making conventional therapy for periodontitis more challenging. This novel study combines thermosensitive in situ hydrogel with microparticles (MPs) to enhance the targeted delivery of metronidazole (MET) to the periodontal pocket. Polycaprolactone (PCL) polymer was utilized to produce bacteria-sensitive MPs. Additionally, the study assessed the attributes of MPs and demonstrated an enhancement in the in vitro antibacterial efficacy of MPs towards Staphylococcus aureus (SA) and Escherichia coli (EC). Subsequently, we incorporated MET-MPs into thermosensitive in situ hydrogel formulations using chitosan. The optimized formulations exhibited stability, appropriate gelation temperature, mucoadhesive strength, and viscosity. In vitro permeation tests showed selective and prolonged drug release against SA and EC. Ex vivo experiments demonstrated no significant differences between in situ hydrogel containing pure MET and MET-MPs in biofilm quantity, bacterial counts, and metabolic activity in biofilms. According to in vitro tests and the effectiveness of the antibacterial activity, this study has exhibited a novel methodology for more efficacious therapies for periodontitis. This study aims to utilize MET in MPs to improve its effectiveness, enhance its antibacterial activity, and improve patient treatment outcomes. In further research, the efficacy of the treatment should be investigated in vivo using an appropriate animal model.

Nanoparticles capped with natural products can be a cost-effective alternative to treat drug-resistant nosocomial infections. Therefore, silibinin-loaded chitosan-capped silver nanoparticles (S-C@AgNPs) were synthesized to evaluate their antimicrobial and anti-inflammatory potential. The S-C@AgNPs plasmon peak was found at 430 nm and had a particle size distribution of about 130 nm with an average hydrodynamic diameter of 101.37 nm. The Scanning Electron Microscopy images showed the presence of sphere-shaped homogeneous nanoparticles. The Fourier Transform Infrared Spectroscopy analysis confirmed the loading of silibinin and chitosan on the AgNPs surface. The minimum inhibitory concentration of the S-C@AgNPs was reported between 3.12 μg/ml to 12.5 μg/ml and a minimum bactericidal concentration between 6.25 μg/ml to 25 μg/ml against drug-resistant nosocomial pathogens. Moreover, concentration-dependent significant inhibition of the biofilm formation was reported against P. aeruginosa (70.21%) and K. pneumoniae (71.02%) at 30 μg/ml, and the highest destruction of preformed biofilm was observed at 100 μg/ml against P. aeruginosa (89.74%) and K. pneumoniae (77.65%) as compared to individual bacterial control. Additionally, the fluorescence live/dead assay for bacterial biofilm confirmed that 100 µg/ml effectively inhibits the biofilm formed by these pathogens. S-C@AgNPs also showed anti-inflammatory activity, which is evident by the significant decrease in the proinflammatory cytokines and chemokines level in THP1 cells treated with LPS. This study concluded that S-C@AgNPs have potent antimicrobial, antibiofilm, and anti-inflammatory properties and could be a potential option for treating drug resistant nosocomial infections.

The utilization of polymethyl methacrylate (PMMA) bone cement is employed for the purpose of stabilizing fractured vertebral bodies. The existence of a mechanical imbalance in hard polymethylmethacrylate (PMMA) bone cement has the potential to increase the likelihood of a fracture occurring in the neighbouring vertebral body. In order to reduce potential difficulties, the primary goal of this study is to investigate the potential benefits of increasing PMMA bone cement's bioactivity and lowering its elastic modulus. The incorporation of a 10% volume fraction of hyaluronic acid (HyA) and polyethylene glycol (PEG) into the bone cement led to an improvement in the bioactivity and decreasing of elastic modulus of polymethylmethacrylate (PMMA). The integration of HyPE gel phase presents several advantages over pure PMMA bone cement, including enhanced setting parameters, improved degradability, and increased biocompatibility. The gel phase is additionally accountable for a reduction in the elastic modulus of polymethylmethacrylate (PMMA) bone cement. In addition, the existence of a porous structure that arises from the degradation of the HyPE gel phase delivers a significant amount of room, thereby enhancing the process of bone regeneration when implanted in the femur of rabbits. The utilization of HyPE in PMMA has been shown through comprehensive µ-CT analysis to enhance bone formation, thereby promoting osteointegration at the implantation site. Furthermore, the histological analysis demonstrated the existence of osteogenic activity in the PMMA polyethylene glycol supplemented with 10% HyA and 10% PEG after a 2-month period subsequent to implantation.

Docetaxel is one of the most effective and safe chemotherapy drugs according to the World Health Organization, but its clinical use has been discontinued due to its various side effects. To reduce these side effects, the amount of docetaxel drug should be kept at the most effective level, it should be monitored in body fluids. Due to the limitations of traditional analytical methods used for this purpose, such as expensive and low sensitivity, labor-intensive and time-consuming complex preliminary preparation, efficient methods are required for the determination of the docetaxel level in the body. The increasing demand for the development of personalized therapy has recently spurred significant research into biosensors for the detection of drugs and other chemical compounds. In this study, an electrochemical-based portable nanobiosensor system was developed for the rapid, low-cost, and sensitive determination of docetaxel. In this context, mg-p(HEMA)-IMEO nanoparticles to be used as nanobiosensor bioactive layer was synthesized, characterized, and docetaxel determination conditions were optimized. According to the results obtained, the developed nanobiosensor system can detect docetaxel with a sensitivity of 2.22 mg/mL in a wide calibration range of 0.25-10 mg/mL, in only 15 min, in mixed media such as commercially available artificial blood serum and urine. determined. We concluded that the developed nanobiosensor system can be successfully used in routine drug monitoring as a low-cost biomedical device capable of direct, rapid, and specific drug determination within the scope of personalized treatment, providing point-of-care testing.

Titanium (Ti) implants are widely used in orthopedic and dental applications due to their excellent biocompatibility and mechanical properties. However, bacterial adhesion and subsequent biofilm formation on implant surfaces pose a significant risk of postoperative infections and complications. Conventional surface modifications often lack long-lasting antibacterial efficacy, necessitating the development of novel coatings with enhanced antimicrobial properties. This study aims to develop a novel Ag-TiO₂-OTS (Silver-Titanium dioxide-Octadecyltrichlorosilane, ATO) nanocomposite coating, through a chemical plating method. By employing a 'resist-killing-disintegrate' approach, the coating is designed to inhibit bacterial adhesion effectively, and facilitate pollutant removal with lasting effects. Characterization of the coatings was performed using spectroscopy, electron microscopy, and contact angle analysis. Antibacterial efficacy, quantitatively evaluated against E. coli and S. aureus over 168 h, showed a significant reduction in bacterial adhesion by 76.6% and 66.5% respectively, and bacterial removal rates were up to 83.8% and 73.3% in comparison to uncoated Ti-base material. Additionally, antibacterial assays indicated that the ratio of the Lifshitz-van der Waals apolar component to electron donor surface energy components significantly influences bacterial adhesion and removal, underscoring a tunable parameter for optimizing antibacterial surfaces. Biocompatibility assessments with the L929 cell line revealed that the ATO coatings exhibited excellent biocompatibility, with minimal cytotoxicity and no significant impact on cell proliferation or apoptosis. The ATO coatings provided a multi-functionality surface that not only resists bacterial colonization but also possesses self-cleaning capabilities, thereby marking a substantial advancement in the development of antibacterial coatings for medical implants.

In the current study, we aimed to design an individual hybrid silibinin nano-delivery system consisting of ZnO and BSA components to study its antioxidant activity and apoptotic potential on human pancreatic, breast, lung, and colon cancer cell lines. The folate-linked ZnO-decorated bovine serum albumin/silibinin nanoparticles (FZBS-NP) were synthesized and characterized by FTIR, FESEM, DLS, and zeta potential analysis. The FZBS-NP's cytotoxicity was evaluated by measuring the cancer cells' (MCF-7, A549, HT-29, and Panc) viability. Moreover, the apoptotic potential of the nanoparticles was studied by conducting several analyses including AO/PI and DAPI cell staining analysis, apoptotic gene expression profile (BAX, BCL2, and Caspase-8) preparation, and FITC Annexin V/PI flow cytometry. Finally, both antioxidant assays (ABTS and DPPH) were utilized to analyze the FZBS-NPs' antioxidant activities. The 152-nm FZBS-NP significantly induced the selective apoptotic death on the MCF-7, A549, HT-29, Panc, and Huvec cancer cells by increasing the SubG1 cell population following the increased treatment concentrations of FZBS-NP. Moreover, the FZBS-NPs exhibited powerful antioxidant activity. The BSA component of the FZBS-NPs delivery system improves the ability of the nanoparticles to gradually release silibinin and ZnO near the cancer cells. On the other hand, considering the powerful antioxidant activity of FZBS-NP, they have the potential to selectively induce apoptosis in human colon and breast cancer cells and protect normal types, which makes it an efficient safe anticancer compound. However, to verify the FZBS-NP anti-cancer efficiency further cancer and normal cell lines are required to measure several types of apoptotic gene expression.

Recent advancements in tissue engineering have witnessed luffa-derived scaffolds, exhibiting their exceptional potential in cellular proliferation, biocompatibility, appropriate interconnectivity, and biomechanical strength. In vivo studies involved implanting fabricated scaffolds subcutaneously in Wistar rats to evaluate their impact on the heart, liver, and kidneys. This approach provided a safe and minimally invasive means to evaluate scaffold compatibility with surrounding tissues. Male Wistar rats were categorized into four distinct groups, Group A, B, C, and D are referred to as 3% LC implanted scaffolds, 5% LC implanted scaffolds, control (without luffa scaffolds), and Sham (without any scaffold implantation), respectively. Histological analysis in all the groups indicated that the animal models did not exhibit any signs of inflammation or toxicity, suggesting favorable tissue response to the implanted scaffolds. Initial observations revealed elevated levels of enzymes and biomarkers in the experimental groups after a 24 h interval, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, creatine kinase-MB (CK-MB), and serum creatinine. However, these parameters normalized 3 weeks post-implantation, with no significant increase compared to the control groups, suggesting that the implanted luffa-based scaffolds did not induce adverse effects on the heart, liver, and kidneys. Furthermore, the scaffold's significant pore size and porosity enable it to release drugs, including antibacterial medications. This study demonstrates promising results, indicating excellent scaffold porosity, sustained drug release, affirming the in vivo biocompatibility, absence of inflammatory responses, and overall tissue compatibility highlighting the immense potential of these luffa-based scaffolds in various tissue engineering and regenerative medicine applications.

Itraconazole (ITZ) is one of the broad-spectrum antifungal agents for treating fungal keratitis. In clinical use, ITZ has problems related to its poor solubility in water, which results in low bioavailability when administered orally. To resolve the issue, we formulated ITZ into the inclusion complex (ITZ-IC) system using β-cyclodextrin (β-CD), which can potentially increase the solubility and bioavailability of ITZ. The molecular docking study has confirmed that the binding energy of ITZ with the β-CD was -5.0 kcal/mol, indicating a stable conformation of the prepared inclusion complex. Moreover, this system demonstrated that the inclusion complex could significantly increase the solubility of ITZ up to 4-fold compared to the pure drug. Furthermore, an ocular drug delivery system was developed through dissolving microneedle (DMN) using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymeric substances. The evaluation results of DMN inclusion complexes (ITZ-IC-DMN) showed excellent mechanical strength and insertion ability. In addition, ITZ-IC-DMN can dissolve rapidly upon application. The ex vivo permeation study revealed that 75.71% (equivalent to 3.79 ± 0.21 mg) of ITZ was permeated through the porcine cornea after 24 h. Essentially, ITZ-IC-DMN exhibited no signs of irritation in the HET-CAM study, indicating its safety for application. In conclusion, this study has successfully developed an inclusion complex formulation containing ITZ using β-CD in the DMN system. This approach holds promise for enhancing the solubility and bioavailability of ITZ through ocular administration.