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The treatment of infective bone defects remains a considerable challenge for orthopedic surgeons, primarily due to the complexities of infection control and the unsatisfactory healing of bone tissue. To solve this challenge, we have designed core/shell nanoparticles to loaded with antibacterial and osteogenic agents. Specifically, magnetocaloric CoFe2O4 (CF) nanoparticles loaded with naringin (NG) and coated with mesoporous silica (MS) were developed to construct NG-CF@MS nanoparticles. Subsequently, levofloxacin (LEV) was loaded into the MS coating, yielding NG-CF@MS-LEV nanoparticles capable of dual drug delivery. These nanoparticles were then incorporated into poly l-lactide (PLLA) powder to fabricate magnetically responsive scaffolds, which demonstrated enhanced osteogenesis and antibacterial activity under alternating magnetic field (AMF) conditions. Drug release studies showed a significant increase in NG and LEV release efficiency in the AMF setting, with a 337% increase in NG release and a 196% increase in LEV compared to non-AMF conditions. In vitro experiments further demonstrated that NG-CF@MS-LEV/PLLA scaffolds exhibited excellent osteogenic and antibacterial properties. Under the intervention of the AMF, the scaffolds displayed antibacterial rates of 98.67% and 99.38% against Escherichia coli and Staphylococcus aureus , respectively. Moreover, the scaffolds significantly promoted osteogenic differentiation and mineralization of mouse bone marrow mesenchymal stromal cells (mBMSCs), highlighting their potential as a promising therapeutic approach for repair of infected bone defects. [ABSTRACT FROM AUTHOR]

To date, implant-associated infection is still a significant clinical challenge, which cannot be effectively eliminated by single therapies due to the formation of microbial biofilms. Herein, a pH-responsive nanoplatform was constructed via the in situ growth of zinc sulfide (ZnS) nanoparticles on the surface of Ti3C2 MXene nanosheets, which was subsequently introduced in poly(L -lactic acid) (PLLA) to prepare a composite bone scaffold via selective laser sintering technology. In the acidic biofilm microenvironment, the degradation of ZnS released hydrogen sulfide (H2S) gas to eliminate the biofilm extracellular DNA (eDNA), thus destroying the compactness of the biofilm. Then, the bacterial biofilm became sensitive to hyperthermia, which could be further destroyed under near-infrared light irradiation due to the excellent photothermal property of MXene, finally achieving gas/photothermal synergistic antibiofilm and efficient sterilization. The results showed that the synergistic gas/photothermal therapy for the composite scaffold not only evidently inhibited the formation of biofilms, but also effectively eradicated the eDNA of the already-formed biofilms and killed 90.4% of E. coli and 84.2% of S. aureus under near infrared light irradiation compared with single gas or photothermal therapy. In addition, the composite scaffold promoted the proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Thus, the designed scaffold with excellent biofilm elimination and osteogenesis ability has great potential as an alternative treatment for implant-associated bone infections. [ABSTRACT FROM AUTHOR]

Many traditional Chinese medicine monomers, such as naringin (NG), can regulate the local immune microenvironment to benefit osteogenesis. However, the rapid release of NG from scaffolds severely influences the osteogenesis-promoting effect. Herein, NG was loaded into mesoporous bioglass (MBG) to achieve sustained release through physical adsorption and the barrier role of mesoporous channels, then MBG loaded with NG was added to poly(L -lactic acid) (PLLA) to fabricate composite scaffolds by selective laser sintering (SLS) technology. The results showed that the NG-MBG/PLLA scaffolds could continuously and slowly release NG for 14 days compared with NG/PLLA scaffolds, and the cumulative release amount for the NG-MBG/PLLA scaffolds was 44.26%. In addition, the NG-MBG/PLLA scaffolds can promote the proliferation and osteogenesis differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs). Meanwhile, the composite scaffolds decreased the reactive oxygen species (ROS) level of RAW264.7 under the stimulation of lipopolysaccharide (LPS) and significantly suppressed interleukin-6 (IL-6) and enhanced arginase-1 (Arg-1) protein expressions. Moreover, calcium nodule and alkaline phosphatase production of mBMSCs in a macrophage-conditioned medium for the NG-MBG/PLLA group also evidently increased compared with the PLLA and MBG/PLLA groups. These NG sustained-release composite scaffolds with osteo-immunomodulation function have great application prospects in the clinic. [ABSTRACT FROM AUTHOR]

The insufficient of H2O2 restricts the efficacy of chemodynamic therapy in tumor microenvironment. Calcium peroxide (CaO2) is expected to solve this problem due to its H2O2-evolving ability. However, it prematurely decomposes in the moist air or water before reaching tumor site. In this study, zeolitic imidazolate framework-67 (ZIF-67) was in-situ grown on the surface of CaO2 to construct a pH-responsive CaO2@ZIF-67 system and then incorporated into poly-L-lactic acid (PLLA) to prepare PLLA/CaO2@ZIF-67 scaffold by selective laser sintering technology. On the one hand, ZIF-67 is used as a chemodynamic therapy agent due to the release of cobalt ions after degradation. On the other hand, ZIF-67 can serve as protective layers to prevent premature decomposition of CaO2 due to its hydrophobic properties, and then CaO2 is exposed and reacts with water to form H2O2 after the pH-responsive degradation of ZIF-67 under tumor acidic microenvironment. Results showed that the PLLA/CaO2@ZIF-67 scaffold could sustainedly produce H2O2 under acidic pH and achieve 84.64% antitumor ratio against MG-63 cells. In addition, the scaffold also promoted proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells due to the release of calcium ions. The prepared PLLA/CaO2@ZIF-67 scaffold with chemodynamic antitumor and osteogenic effects has great potential to treat tumorous bone defect. [ABSTRACT FROM AUTHOR]

Photodynamic antimicrobial therapy via producing ROS based on light-responsive nanoparticles has attracted worldwide attention because of the high selectivity and low side effects. However, biofilms and bacterial membranes provide a natural barrier to prevent the penetration of ROS, which impairs the photodynamic antibacterial efficiency of nanoparticles. Photothermal therapy is an effective strategy against biofilms and bacterial membranes because high temperature can destroy the biofilm structure and enhance the membrane permeability. Herein, Bi2S3 nanorods were anchored on the surface of zinc-doped g-C3N4 (ZnCN) nanosheets to construct a ZnCN-Bi2S3 nanocomposite; then, it was incorporated into poly-l-lactic acid and prepared into scaffolds by the selective laser sintering technology. Bi2S3 nanorods not only endowed the scaffold with an excellent photothermal property but also strengthened the photodynamic effect of ZnCN nanosheets after forming the nanocomposite. The results showed that this nanocomposite had a lower recombination rate of photogenerated electron–hole pairs and produced higher photocurrent compared to those of the g-C3N4 nanosheets and Bi2S3 nanorods. The scaffold destroyed the biofilm and elevated the bacterial membrane permeability significantly and finally achieved 98.5% antibacterial rate for Staphylococcus aureus and 96.3% antibacterial rate for Pseudomonas aeruginosa. Encouragingly, the scaffold could also promote chondrogenic differentiation because of the continuous release of Zn ions. The scaffold containing ZnCN-Bi2S3 nanocomposites possessed excellent antimicrobial and cartilage regeneration functions, which displayed great potential in treating tracheal injuries. [ABSTRACT FROM AUTHOR]

Piezoelectric polyvinylidene fluoride (PVDF) provided an opportunity for non-invasive in situ electrical stimulation of cell behavior, yet its electroactive β phase was difficult to obtain due to its instability in the molten state. Herein, polyaniline (PANI) protrusions were in situ oxidation-polymerized on molybdenum disulfide (MoS2) nanosheets (PANI-MoS2). Then, PANI-MoS2 was introduced into laser additive-manufactured PVDF scaffolds. On the one hand, PANI protrusions produced steric hindrance between adjacent MoS2 nanosheets and inhibited the stacking and aggregating of MoS2. On the other hand, PANI-MoS2 could serve as a platform to achieve interfacial polarization locking. Specifically, Mo–S dipoles in MoS2 and π electron clouds over the N atom in PANI locked −CH2 dipoles in PVDF through electrostatic and hydrogen bond interactions, respectively, which forced −CH2 to align perpendicularly to the basal plane of MoS2 and bialy to one side of the PVDF main chain, thereby forming a full-reverse planar zigzag configuration of the polarized β phase and maintaining its stable existence. The results demonstrated that the β phase of the scaffolds was significantly increased from 43 to 90%, which resulted in an enhanced electrical output performance. The improved electrical output greatly promoted osteoblast-like cell proliferation and differentiation. Furthermore, owing to the pulling-out effect of MoS2 and improved interfacial stress transfer between MoS2 and the polymer matrix, the mechanical properties of scaffolds were also enhanced. These findings suggested that the piezoelectric scaffolds had great potential in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Rapid bone regeneration in implants is important for successful transplantation. In this regard, we report the development of calcium silicate/zinc silicate (CS/ZS) dual-compound-incorporated calcium phosphate cement (CPC) scaffolds with a three-dimensional poly (lactic-co-glycolic acid) network that synergistically promote bone regeneration. In vitro results demonstrated that the incorporation of CS/ZS dual compounds into the CPC significantly promoted the osteogenic differentiation of stem cells compared to the addition of CS or ZS alone. Moreover, the bone-regeneration efficacy of the composite scaffolds was validated by filling in femur condyle defects in rabbits, which showed that the scaffolds with CS and ZS possessed a great bone repair effect, as evidenced by more new bone formation and a faster scaffold biodegradation compared to the scaffold with CS alone., (© 2024 IOP Publishing Ltd.)

Objective: To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects., Methods: The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively., Results: NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli , and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P <0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P <0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P <0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P >0.05)., Conclusion: NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.

Magnetite (Fe 3 O 4 ) nanoparticles as drug carriers can achieve precise drug target due to their magnetic property. However, they are easy to aggregate in the physiological environment, which obviously limits their application in drug delivery. The development of the Fe-MIL-88B-derived method to construct the Fe 3 O 4 -loaded mesoporous carbon (Fe 3 O 4 /carbon) system is a feasible strategy to solve the issue. First, iron atoms evenly distribute in the organic links through coordination bonds in Fe-MIL-88B. After the carbonization of Fe-MIL-88B, mesoporous carbon acts as a barrier to prevent the aggregation of Fe 3 O 4 nanoparticles. Herein, Fe-MIL-88B particles were fabricated by the hydrothermal method and then pyrolyzed to construct Fe 3 O 4 /carbon systems. Results showed that Fe 3 O 4 nanoparticles uniformly in situ grew on mesoporous carbon generated by the carbonization of organic components. More encouragingly, the Fe 3 O 4 /carbon system loaded with DOX demonstrated pH-responsive DOX release, efficient delivery of DOX into cancer cells, and significant cancer cell killing ability. Therefore, the Fe 3 O 4 /carbon systems prepared by the Fe-MIL-88B-derived method might open up a way for targeted and controlled drug delivery.