Journal of Biomaterials Applications最新文献

Addressing fracture-related infections (FRI) and impaired bone healing remains a significant challenge in orthopedics and stomatology. Researchers aim to address this issue by utilizing biodegradable biomaterials, such as magnesium/poly lactic acid (Mg/PLA) composites, to offer antibacterial properties during the degradation of biodegradable implants. Existing Mg/PLA composites often lack sufficient Mg content, hindering their ability to achieve the desired antibacterial effect. Additionally, research on the anti-inflammatory effects of these composites during late-stage degradation is limited. To strengthen mechanical properties, bolster antibacterial efficacy, and enhance anti-inflammatory capabilities during degradation, we incorporated elevated Mg content into PLA to yield Mg/PLA composites. These composites underwent in vitro degradation studies, cellular assays, bacterial tests, and simulation of the PLA degradation microenvironment. 20 wt% and 40 wt% Mg/PLA composites displayed significant antibacterial properties, with three composites exhibiting notable anti-inflammatory effects. In contrast, elevated Mg content detrimentally impacted mechanical properties. The findings suggest that Mg/PLA composites hold promise in augmenting antibacterial and anti-inflammatory attributes within polymers, potentially serving as temporary regenerative materials for treating bone tissue defects complicated by infections.

Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/β-tricalcium phosphate (β-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications.

This study aimed to construct a nanofibrous wound dressing composed of polyvinyl alcohol (PVA) and chitosan (CS) containing curcumin and Glycyrrhiza glabra root extract to inhibit infection and accelerate wound healing. Loading 10 wt% of G. glabra extract-curcumin (50:50) by electrospinng technique resulted in the formation of nanofibers (NFs) with diameter distribution 303 ± 38 and had a uniform and defect-free morphology. FTIR analysis confirmed the loading of the components without adverse interactions. Also, the results showed extremely high porosity, extraordinary liquid absorption capacity, and complete wettability. In addition, G. glabra extract-curcumin showed significant antioxidant activity and their release profile from NFs was continuous and sustained. Also, the prepared NF could inhibit the growth of both Gram-positive Saureus and Gram-negative E. coli strains. Wound healing evaluation in the infected animal model showed that the NFs caused full wound closure and accelerated skin regeneration. The studies on inhibiting the bacteria growth at the wound site also revealed complete inhibitory effects. Moreover, histopathology studies confirmed the complete regeneration of skin layers, formation of collagen fibers, and angiogenesis. Finally, PVA/CS NFs containing G. glabra extract-curcumin as a multifunctional bioactive wound dressing presented a promising approach for promoting the healing of infected wounds.

Sonography with its non-invasive and deep tissue-penetrating characteristics, not only contributes to promising developments in clinical disease diagnosis but also obtains acknowledgments as a prospective therapeutic approach in the field of tumor treatment. However, it remains a challenge for sonography simultaneously to achieve efficient imaging and therapeutic functionality. Here, we present an innovative integrated diagnosis and treatment paradigm by developing the nanomedicine of percarbamide-bromide-mesoporous organosilica spheres (MOS) with RGD peptide modification (PBMR) by loading percarbamide and bromide in MOS which were prepared by a one-step O/W microemulsion method. The PBMR nanomedicine effectively modifies the tumor acoustic environment to improve sonoimaging efficacy and induces sonochemical reactions to enhance the production of reactive oxygen species (ROS) for tumor treatment efficiency under sonography. The combination of PBMR nanomedicine and SDT achieved multiple ROS generation through the controlled sonochemical reactions and significantly boosted the potency of sonodynamic therapy and induced significant tumor regression with non-invasive tissue penetrability and minimizing damage to healthy tissues. Simultaneously, the generation of oxygen gas in the sonochemical process augments ultrasound reflection, resulting in a 4.9-fold increase in imaging grayscale. Our research establishes an effective platform for the synergistic integration of sonoimaging and sonodynamic antitumor therapy, offering a novel approach for precise antitumor treatment in the potential clinical applications.

Background: Diclofenac sodium (DS) and celecoxib (CEL) are primary anti-inflammatory agents used in the treatment of osteoarthritis (OA). Formulating these drugs into extended-release versions can effectively address the issue of multiple daily doses. In this study, we designed and synthesized a novel poly(lactic-co-glycolic acid) (PLGA) nanoliposome as a dual-drug delivery sustained-release formulation (PPLs-DS-CEL) to achieve long-lasting synergistic treatment of OA with both DS and CEL.

Methods: PPLs-DS-CEL was synthesized by the reverse evaporation method and evaluated for its physicochemical properties, encapsulation efficiency, drug release kinetics and biological properties. A rat OA model was established to assess the therapeutic efficacy and biosafety of PPLs-DS-CEL.

Results: The particle size of PPLs-DS-CEL was 218.36 ± 6.27 nm, with a potential of 32.56 ± 3.28 mv, indicating a homogeneous vesicle size. The encapsulation of DS and CEL by PPLs-DS-CEL was 95.18 ± 4.43% and 93.63 ± 5.11%, with drug loading of 9.56 ± 0.32% and 9.68 ± 0.34%, respectively. PPLs-DS-CEL exhibited low cytotoxicity and hemolysis, and was able to achieve long-lasting synergistic analgesic and anti-inflammatory therapeutic effects in OA through slow release of DS and CEL, demonstrating good biosafety properties.

Conclusion: This study developed a novel sustained-release nanoliposomes formulation capable of co-loading two drugs for the long-acting synergistic treatment of OA. It offers a new and effective therapeutic strategy for OA treatment in the clinic settings and presents a promising approach for drug delivery systems.

This study addresses the morphological and chemical characterization of PGS scaffolds after (6, 12, 18, 24, and 30 min) residence in undoped pyrrole plasma (PGS-PPy) and the evaluation of cell viability with human dental pulp stem cells (hDPSCs). The results were compared with a previous study that used iodine-doped pyrrole (PGS-PPy/I). Analyses through SEM and AFM revealed alterations in the topography and quantity of deposited PPy particles. FTIR spectra of PGS-PPy scaffolds confirmed the presence of characteristic absorption peaks of PPy, with higher intensities observed in the nitrile and -C≡C- groups compared to PGS-PPy/I scaffolds, while raman spectra indicated a lower presence of polaron N⁺ groups. On the other hand, PGS scaffolds modified with PPy exhibited lower cytotoxicity compared to PGS-PPy/I scaffolds, as evidenced by the Live/Dead assay. Furthermore, the PGS-PPy scaffolds at 6 and 12 min, and particularly the PGS-PPy/I scaffold at 6 min, showed the best results in terms of cell viability by the fifth day of culture. The findings of this study suggest that undoped pyrrole plasma modification for short durations could also be a viable option to enhance the interaction with hDPSCs, especially when the treatment times range between 6 min and 12 min.

Introduction: Deep vein thrombosis (DVT) is a major cause of cardiovascular disease-related deaths worldwide and is considered a thrombotic inflammatory disorder. IL-1β, as a key promoter of venous thrombus inflammation, is a potential target for DVT treatment. Constructing a nanocarrier system for intracellular delivery of siIL-1β to silence IL-1β may be an effective strategy for alleviating DVT. Methods: ELISA was used to detect the expression levels of IL-1β and t-PA in the serum of DVT patients and healthy individuals. In vitro, HUVEC cells were treated with IL-1β, and changes in VWF and t-PA expression levels were assessed. PBAE/MCM-41@siIL-1β (PM@siIL-1β) nano-complexes were synthesized, the characterization and biocompatibility of PM@siIL-1β were evaluated. A rat hind limb DVT model was established, and PM@siIL-1β was used to treat DVT rats. Morphology of the inferior vena cava, endothelial cell count, IL-1β, vWF, and t-PA levels, as well as changes in the p38 MAPK and NF-κB pathways, were examined in the different groups. Results: IL-1β and t-PA were highly expressed in DVT patients, and IL-1β treatment induced a decrease in VWF levels and an increase in t-PA levels in HUVEC cells. The synthesized PM@siIL-1β exhibited spherical shape, good stability, high encapsulation efficiency, and high drug loading capacity, with excellent biocompatibility. In the DVT model rats, the inferior vena cava was filled with blood clots, endothelial cells increased, IL-1β and VWF levels significantly increased, while t-PA levels were significantly downregulated. Treatment with PM@siIL-1β resulted in reduced thrombus formation, decreased endothelial cell count, and reversal of IL-1β, VWF, and t-PA levels. Furthermore, PM@siIL-1β treatment significantly inhibited p38 phosphorylation and upregulation of NF-κB expression in the DVT model group. Conclusion: IL-1β can be considered a therapeutic target for suppressing DVT inflammation. The synthesized PM@siIL-1β achieved efficient delivery and gene silencing of siIL-1β, demonstrating good therapeutic effects on rat hind limb DVT, including anti-thrombotic and anti-inflammatory effects, potentially mediated through the p38 MAPK and NF-κB pathways.

Triamcinolone acetonide (TA) is a corticosteroid, and widely used in the treatment of eye diseases such as macular edema, proliferative vitreoretinopathy, and chronic uveitis. It's also used in diseases such as osteoarthritis and rheumatoid arthritis. Despite the width of its usage, it has toxicity in the eye. Nanogels are advantageous in applying toxic and low bioavailability drugs thanks to their swelling ability and stability. In the presented study, to minimize the disadvantages of TA, and to reach the drug into the back segment of the eye, TA-loaded chitosan (CS) nanogel (CS-TA Nanogel) has been prepared, and in vitro characterized. CS-TA nanogels were prepared by ionic gelation and characterized by SEM, FTIR, and TGA. Drug release profile, and in vitro cytotoxicity was determined to evaluate the efficacy of nanogels for intravitreal eye applications. DNA damage, and oxidative stress caused by nanogels in eye endothelial cells were investigated. CS and CS-TA nanogels were synthesized in the sizes range 200-300 nm with an overall positive charge surface. The loading efficiency of TA on nanogels was determined as 50%. Cells exposed to 250 µg/ml free TA showed 74% viability, while this rate was 90% in cells exposed to CS-TA nanogels. 8-OHdG levels were determined as 54.93 ± 1.118 ng/mL in control cells and 92.47 ± 0.852 ng/mL in cells exposed to 250 µg/ml TA. TA both induces oxidative stress and causes DNA damage in HRMEC cells. However, administration of TA with carrier increased cell viability, total antioxidant capacity, and reduced oxidative DNA damage.

Objective: Fungal keratitis (FK) usually develops to a poor clinical prognosis due to the fungal invasion and excessive inflammatory reaction. In order to enhance the therapeutic effect of natamycin (NAT), we used the anti-inflammatory biological polysaccharide bletilla striata polysaccharide (BSP) combined with NAT to prepare a new eye drop -- oxidized bletilla striata polysaccharide-natamycin (OBN).

Methods: UV-vis, FT-IR, and fluorescence spectroscopy were used to identify the synthesis of OBN. Biocompatibility of OBN was determined by CCK-8, scratch assay, and corneal toxicity test. RAW264.7 cells and C57BL/6 mice were stimulated with A. fumigatus and treated with PBS, OBN, or NAT. The anti-inflammatory activity of OBN was detected by RT-PCR and ELISA. In mice with FK, the clinical scores were used to evaluate the effect of OBN; HE staining was performed to assess the corneal pathological changes; MPO assay and immunofluorescence staining were used to investigate neutrophil infiltration.

Results: OBN was synthesized by combining oxidized bletilla striata polysaccharide (OBSP) with NAT through Schiff base reaction. OBN did not affect cell viability at a concentration of 160 μg/mL in HCECs, RAW264.7 cells, and mouse corneas. OBN versus NAT significantly improved the prognosis of A. fumigatus keratitis by reducing disease severity, neutrophil infiltration, and expression of inflammatory factors in vivo. Additionally, OBN treatment down-regulated the mRNA and protein expression levels of inflammatory factors IL-1β, TNF-α, and IL-6 in RAW264.7 and mouse models.

Conclusion: OBN is a compound prepared by covalently linking OBSP to the imino group of NAT through Schiff base reaction. OBN treatment down-regulated inflammation and improved the prognosis of mice with A. fumigatus keratitis.

Novel calcium phosphate cements (CPCs) that can be resorbed into the human body need to be developed. One approach for improving bioresorbability is reducing the content of calcium phosphate in CPCs; however, this may induces difficulties in setting the cement and increases the risk of decay. Adding bioresorbable polymers to a liquid solution can shorten the setting time and inhibit decay during setting. A novel bioresorbable polymer, phosphorylated pullulan (PPL), was recently reported. The effect of adding PPL to α-tricalcium phosphate (α-TCP)-based CPCs was examined and compared to that of adding bioresorbable polymers such as collagen, chitosan, and alginate. Collagen did not significantly inhibit the conversion of α-TCP to hydroxyapatite (HA), and its combination with calcium phosphate decreased the setting time and suppressed decay; chitosan decreased the setting time when combined with calcium phosphate; and alginate inhibited the conversion of α-TCP to HA and contributed to suppressing the decay. In contrast, PPL slightly inhibited the conversion of α-TCP to HA; however, its combination with calcium phosphate decreased the setting time. Thus, selecting bioresorbable polymers can help effectively control the properties of CPCs.