MXene-Functionalized Ferroelectric Nanocomposite Membranes with Modulating Surface Potential Enhance Bone Regeneration.

Rapid and effective bone defect repair remains a challenging issue for clinical treatment. Applying biomaterials with endogenous surface potential has been widely studied to enhance bone regeneration, but how to regulate the electric potential and surface morphology of the implanted materials precisely to achieve an optimal bioelectric microenvironment is still a major challenge. The aim of this study is to develop electroactive biomaterials that better mimic the extracellular microenvironment for bone regeneration. Hence, MXene/polyvinylidene fluoride (MXene/PVDF) ferroelectric nanocomposite membranes were prepared by electrospinning. Physicochemical characterization demonstrated that Ti3C2Tx MXene nanosheets were wrapped in PVDF shell layer and the surface morphology and potential were modulated by altering the content of MXene, where uniform distribution of fibers and enhanced electric potential can be obtained and precisely assembled into a natural extracellular matrix (ECM) in bone tissue. Consequently, the MXene/PVDF membranes facilitated cell adhesion, stretching, and growth, showing good biocompatibility; meanwhile, their intrinsic electric potential promoted the recruitment of osteogenic cells and accelerated the differentiation of osteoblast. Furthermore, 1 wt % MXene/PVDF membrane with a suitable surface potential and better topographical structure for bone regeneration qualitatively and quantitatively promoted bone tissue formation in a rat calvarial bone defect after 4 and 8 weeks of healing. The fabricated MXene/PVDF ferroelectric nanocomposite membranes show a biomimetic microenvironment with a sustainable electric potential and optimal 3D topographical structure, providing an innovative and well-suited strategy for application in bone regeneration.

A Retrospective Study on the Transferring Accuracy of a Fully Guided Digital Template in the Anterior Zone.

The accuracy of implant placement with a fully guided digital template can be influenced by many factors, such as arch difference, alveolar bone density, timing of implant placement and open flap. The purpose of this article was to evaluate the factors presumptively affecting the accuracy of implant placement assisted by the fully guided template in the anterior zone. In 40 patients with missing anterior teeth, a total of 52 implants were placed with tooth-borne, fully guided templates after CBCT evaluation, in West China Hospital of Stomatology, Sichuan University. After overlapping the pre-and post-operative DICOM data, measurements were taken in the dental implant planning software (Nobel Clinician®) to calculate linear and angular deviations between virtual placement plan and actual implant placement. Grouping was categorized according to three factors that possibly have an influence on accuracy: arch type (maxilla/mandible), timing of implant placement (immediate/delayed), surgical technique (open flap/flapless). The data was analyzed with independent sample t-test (p < 0.05). The results showed that the apical, coronal, depth and angular mean deviations of implant positions in anterior zone were 1.13 ± 0.39 mm, 0.86 ± 0.33 mm, 0.41 ± 0.66 mm, 3.32 ± 1.65° with the fully guided templates. The accuracy at apex level, coronal level and the angulation were similar between the maxilla and mandible, and the magnitude of all four deviations between immediate and delayed implantation, open flap and flapless technique were small. No statistically significant difference was observed (p > 0.05). Whereas there was significant difference in depth deviation between maxilla and mandible (p < 0.05). Conclusively, the implant site, alveolar bone density, timing of implant placement and surgical techniques merely compromise the implant placement accuracy under the assistance of a fully guided template.

pH and ROS sequentially responsive podophyllotoxin prodrug micelles with surface charge-switchable and self-amplification drug release for combating multidrug resistance cancer.

Multidrug resistance (MDR) is one of the main reasons for tumor chemotherapy failure. Podophyllotoxin (PPT) has been reported that can suppress MDR cancer cell growth; however, effective delivery of PPT to MDR cancer cells is challenged by cascaded bio-barriers. To effectively deliver PPT to MDR cancer cells, a PPT polymeric prodrug micelle (PCDMA) with the charge-conversion capability and self-acceleration drug release function are fabricated, which is composed of a pH and reactive oxygen species (ROS) sequentially responsive PPT-polymeric prodrug and an ROS generation agent, cucurbitacin B (CuB). After reach to tumor tissue, the surface charge of PCDMA could rapidly reverse to positive in the tumor extracellular environment to promote cellular uptake. Subsequently, the PCDMA could be degraded to release PPT and CuB in response to an intracellular high ROS condition. The released CuB is competent for generating ROS, which in turn accelerates the release of PPT and CuB. Eventually, the released PPT could kill MDR cancer cells. The in vitro and in vivo studies demonstrated that PCDMA was effectively internalized by cancer cells and produces massive ROS intracellular, rapid release drug, and effectively overcame MDR compared with the control cells, due to the tumor-specific weakly acidic and ROS-rich environment. Our results suggest that the pH/ROS dual-responsive PCDMA micelles with surface charge-reversal and self-amplifying ROS-response drug release provide an excellent platform for potential MDR cancer treatment.

Platinum (II)-coordinated Portulaca oleracea polysaccharides as metal-drug based polymers for anticancer study.

Novel polysaccharide-platinum conjugated polymers bearing alendronate on Portulaca oleracea polysaccharides (PPS) were designed and synthesized. Their chemical structures and properties were characterized by Fourier transform infrared spectroscopy (FT-IR), 1H NMR and 31P NMR spectroscopy, Thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), UV-vis spectrophotometer (UV-vis) and other analysis methods. The results demonstrated that alendronate can be used as the linker of Portulaca oleracea polysaccharides and platinum compounds. Portulaca oleracea polysaccharides-alendronate (PPS-ALN) conjugates exhibited stronger antioxidant ability than PPS. The cytotoxicity assay to cancer cells was tested in vitro, and the Portulaca oleracea polysaccharides-alendronate-platinum (PPS-ALN-Pt) conjugates strongly inhibited the proliferation of cancer cells than PPS and PPS-ALN. The evaluation of complexes affinity toward supercoiled plasmid DNA, displayed a high DNA interaction. Interestingly, the platinum conjugates displayed immunological competence in HeLa cells by cellular immunofluorescence assay. Besides, the cellular platinum accumulation of PPS-ALN-Pt conjugates was higher than that of cisplatin in HeLa cells, implying that the polysaccharide-platinum conjugated polymers might have a synergistically therapeutic application in metal anticancer drug delivery.