Biomedical materials (Bristol, England)最新文献

This study was designed to deposit nanodiamonds (NDs) on 3D-printed poly-ϵ-caprolactone (PCL) scaffolds and evaluate their effect on the surface topography, hydrophilicity, degradation, andin-vitrocell adhesion compared to untreated PCL scaffolds. The PCL scaffold specimens were 3D-printed by fused deposition modeling (FDM) technique with specific porosity parameters. The 3D-printed specimens' surfaces were modified by NDs deposition followed by oxygen plasma post-treatment using a plasma focus device and a non-thermal atmospheric plasma jet, respectively. Specimens were evaluated through morphological characterization by field emission scanning electron microscope (FESEM), microstructure characterization by Raman spectroscopy, chemical characterization by Fourier transform infrared (FTIR) spectroscopy, hydrophilicity degree by contact angle and water uptake measurements, andin-vitrodegradation measurements (n= 6). In addition,in-vitrobone marrow mesenchymal stem cells adhesion was evaluated quantitatively by confocal microscopy and qualitatively by FESEM at different time intervals after cell seeding (n= 6). The statistical significance level was set atp⩽ 0.05. The FESEM micrographs, the Raman, and FTIR spectra confirmed the successful surface deposition of NDs on scaffold specimens. The NDs treated specimens showed nano-scale features distributed homogeneously across the surface compared to the untreated ones. Also, the NDs treated specimens revealed a statistically significant smaller contact angle (17.45 ± 1.34 degrees), higher water uptake percentage after 24 h immersion in phosphate buffer saline (PBS) (21.56% ± 1.73), and higher degradation rate after six months of immersion in PBS (43.92 ± 0.77%). Moreover, enhanced cell adhesion at all different time intervals was observed in NDs treated specimens with higher nuclei area fraction percentage (69.87 ± 3.97%) compared to the untreated specimens (11.46 ± 1.34%). Surface deposition of NDs with oxygen-containing functional groups on 3D-printed PCL scaffolds increased their hydrophilicity and degradation rate with significant enhancement of thein-vitrocell adhesion compared to untreated PCL scaffolds.

Colon cancer (CC) is one of the most prevalent cancers in the world, and chemotherapy is widely applied to combat it. However, chemotherapy drugs have severe side effects and emergence of multi drug resistance (MDR) is common. This bottleneck can be overcome by niosome nanocarriers that minimize drug dose/toxicity meanwhile allow co-loading of incompatible drugs for combination therapy. In this research, silibinin (Sil) as a hydrophobic drug was loaded into the lipophilic part, and methotrexate (MTX) into the hydrophilic part of niosome by the thin film hydration (TFH) method to form Nio@MS NPs for CT26 colon cancer therapyin vitro. Our results indicated synthesis of ideal niosome nanoparticles (NPs) with spherical morphology, size of ∼100 nm, and a zeta potential of -10 mV. The IC₅₀value for Nio@MS was determined ∼2.6 µg ml^-1, which was significantly lower than MTX-Sil (∼6.86 µg ml^-1), Sil (18.46 µg ml^-1), and MTX (9.8 µg ml^-1). Further, Nio@MS significantly reduced cell adhesion density, promoted apoptosis and increased gene expression level of caspase 3 and BAX while promoted significant downregulation of BCL2. In conclusion, the design and application of niosome to co-administer Sil and MTX can increase the drugs cytotoxicity, reduce their dose and improve anti-cancer potential by combating MDR.

This study aimed to develop and optimize karanjin-loaded ethosomal nanogel formulation and evaluate its efficacy in alleviating symptoms of psoriasis in an animal model induced by imiquimod. These karanjin-loaded ethosomal nanogel, were formulated to enhance drug penetration into the skin and its epidermal retention. Karanjin was taken to formulate ethosomes due to its potential ani-psoriatic activity. Ethosomes were formulated using the cold method using 3²full factorial designs to optimize the formulation components. 9 batches were prepared using two independent variablesX₁: concentration of ethanol andX₂: concentration of phospholipid whereas vesicle size (Y₁) and percentage entrapment efficiency (Y₂) were selected as dependent variables. All the dependent variables were found to be statistically significant. The optimized ethosomal suspension (B3) exhibited a vesicle size of 334 ± 2.89 nm with an entrapment efficiency of 94.88 ± 1.24% and showed good stability. The morphology of vesicles appeared spherical with smooth surfaces through transmission electron microscopy analysis. X-ray diffraction analysis confirmed that the drug existed in an amorphous state within the ethosomal formulation. The optimized ethosome was incorporated into carbopol 934 to develop nanogel for easy application on the skin. The nanogel underwent characterization for various parameters including spreadability, viscosity, pH, extrudability, and percentage drug content. The ethosomal formulation remarkably enhanced the skin permeation of karanjin and increased epidermal retention of the drug in psoriatic skin compared to marketed preparation and pure drug. A skin retention study showed that ethosomal nanogel formulation has 48.33% epidermal retention in 6 h.In vivo,the anti-psoriatic activity of karanjin ethosomal nanogel demonstrated significant improvement in psoriasis, indicated by a gradual decrease in skin thickness and scaling as reflected in the Psoriasis Severity Index grading. Therefore, the prepared ethosomal nanogel is a potential vehicle for improved topical delivery of karanjin for better treatment of psoriasis.

Multiaxial filament winding is an additive manufacturing technique used extensively in large industrial and military manufacturing yet unexplored for biomedical uses. This study adapts filament winding to biomanufacture scalable, strong, three-dimensional microfiber (3DMF) medical device implants for potential orthopedic applications. Polylactide microfiber filaments were wound through a collagen 'resin' bath to create organized, stable orthobiologic implants, which are sized for common ligament (e.g. anterior cruciate ligament) and tendon (e.g. rotator cuff) injuries and can be manufactured at industrial scale using a small footprint, economical, high-output benchtop system. Ethylene oxide or electron beam sterilized 3DMF samples were analyzed by scanning electron microscopy (SEM), underwent ASTM1635-based degradation testing, tensile testing, ISO 10993-based cytocompatibility, and biocompatibility testing, quantified for human platelet-rich plasma (PRP) absorption kinetics, and examined for adhesion of bioceramics and lyophilized collagen after coating. 3DMF implants had consistent fiber size and high alignment by SEM. Negligible mass and strength loss were noted over 4 months in culture. 3DMF implants initially exceeded 1000 N hydrated tensile strength and retained over 70% strength through 4 months in culture, significantly stronger than conventionally produced implants made by fused fiber deposition 3D printing. 3DMF implants absorbed over 3xtheir weight in PRP within 5 min, were cytocompatible and biocompatible in vivo in rabbits, and could readily bind tricalcium phosphate and calcium carbonate coatings discretely on implant ends for further orthobiologic material functionalization. The additive manufacturing process further enabled engineering implants with suture-shuttling passages for facile arthroscopic surgical delivery. This accessible, facile, economical, and rapid microfiber manufacturing platform presents a new method to engineer high-strength, flexible, low-cost, bio-based implants for orthopedic and extended medical device applications.

Artificial bone substitutes for bone repair and reconstruction still face enormous challenges. Previous studies have shown that calcium magnesium phosphate cements (CMPCs) possess an excellent bioactive surface, but its clinical application is restricted due to short setting time. This study aimed to develop new CMPC/carboxymethyl chitosan (CMCS) comg of mixed powders of active MgO, calcined MgO and calcium dihydrogen phosphate monohydrate. With this novel strategy, it can adjust the setting time and improve the compressive strength. The results confirmed that CMPC/CMCS composite bone cements were successfully developed with a controllable setting time (18-70 min) and high compressive strength (87 MPa). In addition, the composite bone cements could gradually degrade in PBS with weight loss up to 32% at 28 d. They also promoted the proliferation of pre-osteoblasts, and induced osteogenic differentiation. The findings indicate that CMPC/CMCS composite bone cements hold great promise as a new type of bone repair material in further and in-depth studies.

Melt electrowriting (MEW) is an additive manufacturing technique that harnesses electro-hydrodynamic phenomena to produce 3D-printed fibres with diameters on the scale of 10s of microns. The ability to print at this small scale provides opportunities to create structures with incredibly fine resolution and highly defined morphology. The current gold standard material for MEW is poly(ϵ-caprolactone) (PCL), a polymer with excellent biocompatibility but lacking in chemical groups that can allow intrinsic additional functionality. To provide this functionality while maintaining PCL's positive attributes, blending was performed with a Poly(Ethylene Glycol) (PEG)-based Acrylate endcapped Urethane-based Precursor (AUP). AUPs are a group of polymers, built on a backbone of existing polymers, which introduce additional functionality by the addition of one or more acrylate groups that terminate the polymer chain of a backbone polymer. By blending with a 20kDa AUP-PEG in small amounts, it is shown that MEW attributes are preserved, producing high-quality meshes. Blends were produced in various PCL:AUP weight ratios (100:0, 90:10 and 0:100) and processed into both solvent-cast films and MEW meshes that were used to characterise the properties of the blends. It was found that the addition of AUP-PEG to PCL significantly increases the hydrophilicity of structures produced with these polymers, and adds swelling capability compared to the non-swelling PCL. The developed blend (90:10) is shown to be processable using MEW, and the quality of manufactured scaffolds is evaluated against pure PCL scaffolds by performing scanning electron microscopy image analysis, with the quality of the novel MEW blend scaffolds showing comparable quality to that of pure PCL. The presence of the functionalisable AUP material on the surface of the developed scaffolds is also confirmed using fluorescence labelling of the acrylate groups. Biocompatibility of the MEW-processable blend was confirmed through a cell viability study, which found a high degree of cytocompatibility.

The natural healing process of extraction socket and traditional socket plug material could not prevent buccal bone wall resorption and down growth of epithelium from the socket orifice. A multiphase bioactive socket plug (BP) is designed to overcome the natural healing process by maintaining the three-dimensional (3D) volume of extraction sockets, particularly in sockets with wall defects, and later provide sufficient alveolar bone volume for implant placement. The study aimed to fabricate and evaluate the physical, chemical, and biological performance of BPin vitro. The BP was fabricated through freeze-drying and layer-by-layer assembly, comprised of a base serving as a scaffold, a central portion for promoting bone regeneration, an upper buccal portion for maintaining alveolar socket dimension with a covering collagen membrane (Memb) on the top and upper buccal surface to prevent soft tissue infiltration. The BP as the experimental group and a pure collagen plug (CP) as the control group were investigated and compared. Radiograph, scanning electron microscopy, and energy-dispersive spectroscopy mapping confirmed that the four-part BP was successfully assembled and fabricated. Swelling rate analysis indicated that BP, CP, and Memb reached swelling equilibrium within 1 hour. BP exhibited a high remaining weight percentage in collagenase solution (68.81 ± 2.21% on day 90) and sustained calcium ion release, reaching the maximum 0.13 ± 0.04 mmol l^-1on day 14. In biological assays, BP exhibited excellent cell proliferation (The OD value increased from 0.02 on day 1 to 0.23 on day 21.). The BP group exhibited higher alkaline phosphatase activity and osteocalcin content than the CP group within 21 days. Memb and BP exhibited outstanding barrier function, as evidenced by Hematoxylin and eosin staining. In summary, the multiphase bioactive socket plug represents a promising scaffold for alveolar ridge preservation application.

N-chloro-N-fluorobenzenesulfonylamide (CFBSA), was a novel chlorinating reagent, which exhibits potential antibacterial activities. In this study, CFBSA was confirmed as a wide-broad antimicrobial and bactericidal drug against different gram-negative bacteria, gram-positive bacteria and fungi, while it was found to have low cytotoxicity for eukaryotic cells. In addition, microorganism morphology assay and oxidative stress test was used to determine the antimicrobial mechanisms of CFBSA. According to the results, CFBSA probably had a target on cell membrane and killed microorganism by disrupting its cell membrane. Then, CFBSA was first combined with poly(L-lactide-co-caprolactone) (PLCL)/SF via electrospinning and applied in wound dressings. The characterization of different PLCL/SF of CFBSA-loaded nanofibrous mats was investigated by SEM, water contact angle, Fourier transform infrared spectroscopy, cell compatibility and antimicrobial test. CFBSA-loaded PLCL/SF nanofibrous mats showed excellent antimicrobial activities. In order to balance of the biocompatibility and antibacterial efficiency, SP-2.5 was selected as the ideal loading concentration for further application of CFBSA-loaded PLCL/SF. In conclusion, the electrospun CFBSA-loaded PLCL/SF nanofibrous mat with its broad-spectrum antimicrobial and bactericidal activity and good biocompatibility showed enormous potential for wound dressing.

Stopping postoperative soft tissue adhesions is one of the most challenging clinical problems that needs to be addressed urgently to avoid secondary injury and pain to patients. Currently, membrane materials with anti-protein adsorption and antibacterial activity are recognized as an effective and promising anti-adhesion barrier to prevent postoperative adhesion and the recurrent adhesion after adhesiolysis. Herein, poly(amino acid) (PAA), which is structurally similar to collagen, is selected as the membrane base material to successfully synthesize PAA-5 membranes with excellent mechanical and degradation properties by in-situ melt polymerization and hot-melt film-forming technology. Subsequently, the co-deposition of polydopamine/polysulfobetaine methacrylate (PDA/PSBMA) coatings induced by CuSO₄/H₂O₂on PAA-5 membranes results in the formation of PDC-5S and PDC-10S, which exhibit excellent hemocompatibility, protein antifouling properties, and cytocompatibility. Additionally, PDC-5S and PDC-10S demonstrated significant antibacterial activity againstEscherichia coliandStaphylococcus aureus, with an inhibition rate of more than 90%. As a result, this study sheds light on newly discovered PAA membranes with anti-protein adsorption and antibacterial activity can sever as one of the promising candidates for the prevention of postoperative peritoneum adhesions.

Sutures are commonly used in surgical procedures and have immense potential for direct drug delivery into the wound site. However, incorporating active pharmaceutical ingredients into the sutures has always been challenging as their mechanical strength deteriorates. This study proposes a new method to produce microspheres-embedded surgical sutures that offer adequate mechanical properties for effective wound healing applications. The study used curcumin, a bioactive compound found in turmeric, as a model drug due to its anti-inflammatory, antioxidant, and anti-bacterial properties, which make it an ideal candidate for a surgical suture drug delivery system. Curcumin-loaded microspheres were produced using the emulsion solvent evaporation method with polyvinyl alcohol (PVA) as the aqueous phase. The microspheres' particle sizes, drug loading (DL) capacity, and encapsulation efficiency (EE) were investigated. Microspheres were melt-extruded with polycaprolactone and polyethylene glycol via a 3D bioplotter, followed by a drawing process to optimise the mechanical strength. The sutures' thermal, physiochemical, and mechanical properties were investigated, and the drug delivery and biocompatibility were evaluated. The results showed that increasing the aqueous phase concentration resulted in smaller particle sizes and improved DL capacity and EE. However, if PVA was used at 3% w/v or below, it prevented aggregate formation after lyophilisation, and the average particle size was found to be 34.32 ± 12.82 μm. The sutures produced with the addition of microspheres had a diameter of 0.38 ± 0.02 mm, a smooth surface, minimal tissue drag, and proper tensile strength. Furthermore, due to the encapsulated drug-polymer structure, the sutures exhibited a prolonged and sustained drug release of up to 14 d. Microsphere-loaded sutures demonstrated non-toxicity and accelerated wound healing in thein vitrostudies. We anticipate that the microsphere-loaded sutures will serve as an excellent biomedical device for facilitating wound healing.