Administration of drugs via the buccal route has attracted much attention in recent years. However, developing systems with satisfactory adhesion under wet conditions and adequate drug bioavailability still remains a challenge. Here, we propose a mussel-inspired mucoadhesive film. Ex vivo models show that this film can achieve strong adhesion to wet buccal tissues (up to 38.72 ± 10.94 kPa). We also demonstrate that the adhesion mechanism of this film relies on both physical association and covalent bonding between the film and mucus. Additionally, the film with incorporated polydopamine nanoparticles shows superior advantages for transport across the mucosal barrier, with improved drug bioavailability (~3.5-fold greater than observed with oral delivery) and therapeutic efficacy in oral mucositis models (~6.0-fold improvement in wound closure at day 5 compared with that observed with no treatment). We anticipate that this platform might aid the development of tissue adhesives and inspire the design of nanoparticle-based buccal delivery systems.

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.

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. To improve the efficacy and reduce side effects of anticancer drugs, nanoparticle drug delivery systems (DDSs) have been widely explored in the past few decades 1. Graphene, one of the most popular nanoparticles, has attracted tremendous attentions in the DDSs field due to its unique physical and chemical properties 2. Graphene is a two-dimensional single layer constituted of sp 2-hybridized carbon, which could supply a excellent drug-load ability with its high specific surface area. As a derivatives of graphene, graphene oxide (GO), which could be detected to have hydroxyl, carbonyl, carboxyl and epoxide functional groups on thesurfaces of each shee 3. The presence of those reactive functional groups imparts GO with excellent aqueous solubility, biocompatibility and multi-functionalities, which is essential for the delivery of anticancer drugs 4. Because of the unique properties of graphene oxide (GO), many efforts have been made to load anticancer drugs onto GO efficiently by either non-covalent or covalent bonds 5. For instance, Dai and colleagues 6 first attached hydrophobic aromatic molecules such as a camptothecin analogue (SN38) to the GO surface. The resulting GO-SN38 complex exhibits enhanced solubility and higher anticancer ability than the original SN38 prodrug does. In our previous study 7 , cisplatin (Pt) was carried by PEG-functionalized GO (pGO), and the as-prepared GO-Pt exhibits improved drug loading efficiency and enhance...

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 Zn 2+ . 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 Zn 2+ 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.

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.