Multi-Mechanism Antibacterial Strategies Enabled by Synergistic Activity of Metal-Organic Framework-Based Nanosystem for Infected Tissue Regeneration.

Drug-resistant bacterial infection impairs tissue regeneration and is a challenging clinical problem. Metal-organic frameworks (MOFs)-based photodynamic therapy (PDT) opens up a new era for antibiotic-free infection treatment. However, the MOF-based PDT normally encounters limited photon absorbance under visible light and notorious recombination of photogenerated holes and electrons, which significantly impede their applications. Herein, a MOFs-based nanosystem (AgNPs@MOFs) with enhanced visible light response and charge carrier separation is developed by modifying MOFs with silver nanoparticles (AgNPs) to improve PDT efficiency. The AgNPs@MOFs with enhanced photodynamic performance under visible light irradiation mainly disrupt bacteria translation process and the metabolism of purine and pyrimidine. In addition, the introduction of AgNPs endows nanosystems with chemotherapy ability, which causes destructive effect on bacterial cell membrane, including membrane ATPase protein and fatty acids. AgNPs@MOFs show excellent synergistic drug-resistant bacterial killing efficiency through multiple mechanisms, which further restrain bacterial resistance. In addition, biocompatible AgNPs@MOFs pose potential tissue regeneration ability in both Methicillin-resistant Staphylococcus aureus (MRSA)-related soft and hard tissue infection. Overall, this study provides a promising perspective in the exploration of AgNPs@MOFs as nano antibacterial medicine against drug-resistant bacteria for infected tissue regeneration in the future.

pH-Triggered Size-Tunable Silver Nanoparticles: Targeted Aggregation for Effective Bacterial Infection Therapy.

The rapid spread of drug-resistant pathogens threatens human health. To address the current antibacterial dilemma, the development of antibiotic-free strategies using nanotechnology is imperative. In this study, silver nanoparticles (Ag-P&C NPs) with pH-sensitive charge reversal and self-aggregation capacities are successfully synthesized. In the acidic microenvironment of bacterial biofilms, protonation of the surface peptide enhances the affinity of Ag-P&C NPs for bacteria, which can make Ag-P&C NPs prone to target and penetrate into biofilms, and the self-aggregated capacity helps Ag-P&C NPs remain in biofilms for a long time to disrupt bacterial biofilm formation. In addition, biocompatible Ag-P&C NPs are utilized in three types of bacteria-infected animal models. They exhibit an excellent performance in killing bacteria, inhibiting plaque biofilms, and ameliorating inflammatory responses. In conclusion, this study offers new insights into antibiotic-free antibacterial strategies, and exhibits promising application prospects.

The development of magnesium-based biomaterials in bone tissue engineering: A review.

Bone regeneration is a vital clinical challenge in massive or complicated bone defects. Recently, bone tissue engineering has come to the fore to meet the demand for bone repair with various innovative materials. However, the reported materials usually cannot satisfy the requirements, such as ideal mechanical and osteogenic properties, as well as biocompatibility at the same time. Mg-based biomaterials have considerable potential in bone tissue engineering owing to their excellent mechanical strength and biosafety. Moreover, the biocompatibility and osteogenic activity of Mg-based biomaterials have been the research focuses in recent years. The main limitation faced in the applications of Mg-based biomaterials is rapid degradation, which can produce excessive Mg2+ and hydrogen, affecting the healing of the bone defect. In order to overcome the limitations, researchers have explored several ways to improve the properties of Mg-based biomaterials, including alloying, surface modification with coatings, and synthesizing other composite materials to control the degradation rate upon implantation. This article reviewed the osteogenic mechanism and requirement for appropriate degradation rate and focused on current progress in the biomedical use of Mg-based biomaterials to inspire more clinical applications of Mg in bone regeneration in the future.

Sleep - the guarantee of health! Does the environmental perception characteristics of urban residential areas affect residents' sleep quality?

A complex urban living environment and residents' sleep quality are intrinsically linked. Nonetheless, there is little evidence that the residential environment affects sleep quality. Based on the results of subjective questionnaires, this study uses the multiple regression combined with mediation analysis to construct a mechanical model of the impact of urban residential environmental perception characteristics on residents' sleep quality. Moreover, the differences among the influence intensities of the significant factors are compared and the results show that (1) in low-density environments (FAR < 2) and lower floors (4-6), residents sleep longer and have better sleep quality; (2) the environmental quality and service facilities of the physical environment and the sense of safety in the social environment have a significant impact on residents' sleep quality; and (3) the mental health of residents play a significant intermediary role in the relationship between social environment and sleep quality, with the highest effect accounting for 33.88%. The influence mechanisms of various environmental factors in a residential area on sleep quality were revealed and a more refined design basis for a healthy urban living environment, community renewal, and renovation was provided.

Nanoscale Zeolitic Imidazolate Framework-8 Activator of Canonical MAPK Signaling for Bone Repair.

Zeolitic imidazolate framework-8 (ZIF-8) is an important type of metal organic framework and has found numerous applications in the biomedical field. Our previous studies have demonstrated that nano ZIF-8-based titanium implants could promote osseointegration; however, its osteogenic capacity and the related mechanisms in bone regeneration have not been fully clarified. Presented here is a nanoscale ZIF-8 that could drive rat bone mesenchymal stem cell (rBMSC) differentiation into osteoblasts both in vitro and in vivo, and interestingly, nano ZIF-8 exhibited a better osteogenic effect compared with ionic conditions of Zn at the same concentration of Zn2+. Moreover, the cellular uptake mechanisms of the nanoparticles were thoroughly clarified. Specifically, nano ZIF-8 could enter the rBMSC cytoplasm probably via caveolae-mediated endocytosis and macropinocytosis. The intracellular and extracellular Zn2+ released from nano ZIF-8 and the receptors involved in the endocytosis may play a role in inducing activation of key osteogenic pathways. Furthermore, through transcriptome sequencing, multiple osteogenic pathways were found to be upregulated, among which nano ZIF-8 primarily phosphorylated ERK, thus activating the canonical mitogen-activated protein kinase pathway and promoting the osteogenesis of rBMSCs. Taken together, this study helps to elucidate the mechanism by which nano ZIF-8 regulates osteogenesis and suggests it to be a potential biomaterial for constructing multifunctional composites in bone tissue engineering.

ZIF-8-Modified Multifunctional Bone-Adhesive Hydrogels Promoting Angiogenesis and Osteogenesis for Bone Regeneration.

Designing bone adhesives with adhesiveness, antideformation, biocompatibility, and biofunctional effects has great practical significance for bone defect reconstructive treatment, especially for bone graft repair surgery. Here, we designed zeolitic imidazolate framework-8 nanoparticle (ZIF-8 NP)-modified catechol-chitosan (CA-CS) multifunctional hydrogels (CA-CS/Z) to stabilize the bone graft environment, ensure blood supply, promote osteogenic differentiation, and accelerate bone reconstruction. Characterizations confirmed the successful synthesis of CA-CS/Z hydrogels. Hydrogels exhibited advanced rheological properties, reliable mechanical strength, and excellent adhesion for clinical applications. Based on excellent biocompatibility, it could enhance paracrine of the vascular endothelial growth factor (VEGF) in rat bone marrow mesenchymal stem cells (rBMSCs) to ensure blood supply reconstruction in bone defect areas. Furthermore, the ZIF-8 NPs released from the hydrogels could also up-regulate the production and secretion of alkaline phosphatase, collagen 1, and osteocalcin, promoting the osteogenic differentiation of rBMSCs. In addition, the antibacterial properties of CA-CS/Z could also be observed. In vivo experiments further provided a powerful proof that CA-CS/Z promoted vascularized osteogenesis in wound areas by stabilizing bone graft materials and greatly accelerated the speed and healing of bone reconstruction. These results indicate the promising potential of CA-CS/Z hydrogels with promoting implantation stability, angiogenesis, and osteogenesis for bone regeneration applications.

Zeolitic Imidazolate Framework-8 Encapsulating Risedronate Synergistically Enhances Osteogenic and Antiresorptive Properties for Bone Regeneration.

Bisphosphonates (BPs) are routinely administered for the treatment of turnover bone diseases. To avoid the undesirable adverse effects of long-term usage of bisphosphonates and improve their bioavailability in the bone microenvironment, we initially encapsulated risedronate (RIS) molecules inside nanoscale zeolitic imidazolate framework-8 particles (nZIF-8) by a one-step synthesis method to generate RIS@ZIF-8 nanoparticles. RIS@ZIF-8 nanoparticles displayed high loading encapsulation efficiency (64.21 ± 2.48%), good biocompatibility, controlled drug release capacity, and dual effects for bone regeneration. This work explored the potential of RIS@ZIF-8 nanoparticles, which could not only enhance ATP production, induce extracellular matrix (ECM) mineralization, and upregulate the expression levels of osteogenic genes but also effectively inhibit the formation of multinucleated giant osteocasts and decrease the Rankl/Opg ratio. Overall, RIS@ZIF-8 nanoparticles could be a very promising approach to synergistically enhance osteogenic and antiresorptive properties for bone regeneration, which could be utilized for the local treatment of bone defects.

PEGylated nano-graphene oxide as a nanocarrier for delivering mixed anticancer drugs to improve anticancer activity.

Due to their high specific surface area, graphene oxide and graphene oxide-base nanoparticles have great potential both in dual-drug delivery and combination chemotherapy. Herein, we developed cisplatin (Pt) and doxorubicin (DOX) dual-drug-loaded PEGylated nano-graphene oxide (pGO) to facilitate combined chemotherapy in one system. In this study, nano-sized pGO-Pt/DOX ranged around 161.50 nm was fabricated and characterized using zeta-potential, AFM, TEM, Raman, UV-Vis, and FTIR analyses. The drug delivery efficacy of Pt was enhanced through the introduction of pGO, and the final weight ratio of DOX: Pt: pGO was optimized to 0.376: 0.376: 1. In vitro studies revealed that pGO-Pt/DOX nanoparticles could be effectively delivered into tumor cells, in which they induced prominent cell apoptosis and necrosis and exhibited higher growth inhibition than the single drug delivery system or free drugs. The pGO-Pt/DOX induced the most prominent cancer cell apoptosis and necrosis rate with 18.6%, which was observed almost 2 times higher than that of pGO-Pt or pGO-DOX groups. in the apoptosis and necrotic quadrants In vivo data confirmed that the pGO-Pt/DOX dual-drug delivery system attenuated the toxicity of Pt and DOX to normal organs compared to free drugs. The tumor inhibition data, histopathology observations, and immunohistochemical staining confirmed that the dual-drug delivery system presented a better anticancer effect than free drugs. These results clearly indicated that the pGO-Pt/DOX dual-drug delivery system provided the means for combination drug delivery in cancer treatment.

Tazarotene Released from Aligned Electrospun Membrane Facilitates Cutaneous Wound Healing by Promoting Angiogenesis.

Wound treatment is a long-lasting clinical issue. Poor angiogenesis leading to delayed wound closure causes huge challenges for healing. Functional electrospun membranes have been established as an efficient strategy to promote wound recovery by protecting and improving vascular regeneration. Here, we aimed to investigate the effect of tazarotene, an active drug for angiogenesis, loaded in aligned electrospun nanofibrous barrier on a soft tissue wound. This aligned membrane was arranged in a single direction, and tazarotene could be released from its nanofibers sustainably. The in vitro study demonstrated that compared with the random drug-loaded or other control groups, the aligned tazarotene-loaded membranes [poly-caprolactone (PCL)/AT] could stimulate proliferation, migration, angiogenesis, and vascular endothelial growth factor secretion and its gene expression of human umbilical vein endothelial cells. Furthermore, the in vivo model showed that the prepared tazarotene-loaded aligned membrane significantly accelerated the speed of healing, improved the neovascularization and re-epithelialization, and inhibited the inflammatory reaction in the wound area. All these results above indicated that the PCL/AT nanofibrous dressing, which could promote angiogenesis because of both stimulation of structure and chemical signals, is a promising wound-caring material.

Graphene Family Materials in Bone Tissue Regeneration: Perspectives and Challenges.

We have witnessed abundant breakthroughs in research on the bio-applications of graphene family materials in current years. Owing to their nanoscale size, large specific surface area, photoluminescence properties, and antibacterial activity, graphene family materials possess huge potential for bone tissue engineering, drug/gene delivery, and biological sensing/imaging applications. In this review, we retrospect recent progress and achievements in graphene research, as well as critically analyze and discuss the bio-safety and feasibility of various biomedical applications of graphene family materials for bone tissue regeneration.

Evaluation of tooth root surface area using a three-dimensional scanning technique and cone beam computed tomographic reconstruction in vitro.

OBJECTIVE: To study the feasibility of measuring root surface area (RSA) by 3D scanning technique and cone beam computed tomography (CBCT) reconstruction in vitro. DESIGN: Twenty extracted teeth (10 single-rooted teeth and 10 multi-rooted teeth) were collected in this study. The RSA of the extracted teeth was measured by the membrane technique, 3D scanning technique, and CBCT reconstruction. A standard part was also designed to check the accuracy of each method. All statistical analyses were performed using the SPSS software. RESULTS: According to the results of one-way ANOVA, there was no significant difference among the values of RSA measured by the three techniques (p>0.05). The results of Wilcoxon matched-pairs signed-rank test further demonstrated that there was no significant difference among the values of RSA in both single- and multi-rooted teeth measured by the three techniques (p>0.05). CONCLUSIONS: The membrane technique, the 3D scanning technique, and CBCT reconstruction are novel reliable techniques for measuring the RSA in both single- and multi-rooted teeth, which will provide wide clinical applications in the future.