Titanium Carbide MXene Quantum Dots-Modified Hydroxyapatite Hollow Microspheres as pH/Near-Infrared Dual-Response Drug Carriers.

Titanium carbide MXene quantum dots (MQDs) possess intrinsic regulatory properties and selective toxicity to cancer cells. Here, MDQs were selected for the modification of hydroxyapatite (HA) microspheres, and MXene quantum dots-modified hydroxyapatite (MQDs-HA) hollow microspheres with controllable shapes and sizes were prepared as bone drug carriers. The results show that the prepared MQDs-HA hollow microspheres had a large BET surface area (231.2 m2/g), good fluorescence, and low toxicity. In addition, MQDs-HA showed a mild storage-release behavior and good responsiveness of pH and near-infrared (NIR). Thus, the MQDs-HA hollow microspheres have broad application prospects in the field of drug delivery and photothermal therapy.

Construction of nanofibrous scaffolds with interconnected perfusable microchannel networks for engineering of vascularized bone tissue.

Vascularization and bone regeneration are two closely related processes during bone reconstruction. A three-dimensional (3D) scaffold with porous architecture provides a suitable microenvironment for vascular growth and bone formation. Here, we present a simple and general strategy to construct a nanofibrous poly(l-lactide)/poly(ε-caprolactone) (PLLA/PCL) scaffold with interconnected perfusable microchannel networks (IPMs) based on 3D printing technology by combining the phase separation and sacrificial template methods. The regular and customizable microchannel patterns within the scaffolds (spacings: 0.4 mm, 0.5 mm, and 0.6 mm; diameters: 0.8 mm, 1 mm, and 1.2 mm) were made to investigate the effect of microchannel structure on angiogenesis and osteogenesis. The results of subcutaneous embedding experiment showed that 0.5/0.8-IPMs (spacing/diameter = 0.5/0.8) and 0.5/1-IPMs (spacing/diameter = 0.5/1) scaffolds exhibited more vascular network formation as compared with other counterparts. After loading with vascular endothelial growth factor (VEGF), VEGF@IPMs-0.5/0.8 scaffold prompted better human umbilical vein endothelial cells (HUVECs) migration and neo-blood vessel formation, as determined by Transwell migration, scratch wound healing, and chorioallantoic membrane (CAM) assays. Furthermore, the microangiography and rat cranial bone defects experiments demonstrated that VEGF@IPMs-0.5/0.8 scaffold exhibited better performance in vascular network formation and new bone formation compared to VEGF@IPMs-0.5/1 scaffold. In summary, our results suggested that the microchannel structure within the scaffolds could be tailored by an adjustable caramel-based template strategy, and the combination of interconnected perfusion microchannel networks and angiogenic factors could significantly enhance vascularization and bone regeneration.

Manganese-doped gold core mesoporous silica particles as a nanoplatform for dual-modality imaging and chemo-chemodynamic combination osteosarcoma therapy.

In this study, an effective and facile strategy is reported to construct a multifunctional nanoplatform by in situ doping metal manganese on gold core mesoporous silica nanoparticles (Au@MMSN). After further modification of alendronate (Ald) on Au@MMSN, the obtained Au@MMSN-Ald efficiently integrates bone targeted chemo-chemodynamic combination therapy and dual-modality computed tomography/magnetic resonance (CT/MR) imaging into a single platform. In particular, Au@MMSN-Ald exhibits excellent tumor microenvironment responsive drug release efficiency. The doxorubicin hydrochloride (DOX) loaded Au@MMSN-Ald (DOX@Au@MMSN-Ald) is demonstrated with excellent targeted ability toward osteosarcoma. Accordingly, in a specific tumor microenvironment, DOX@Au@MMSN-Ald also displays outstanding combined efficiency for killing cancer cells in vitro and suppressing the osteosarcoma growth in vivo. Benefiting from the Au nanoparticles confined in the core and manganese ions released from the shell, CT and MR dual-modality imaging were performed to verify the effective accumulation of Au@MMSN-Ald at the tumor site. Overall, the constructed DOX@Au@MMSN-Ald nanoparticles integrated imaging guide, responsive drug release and combination therapy, which may provide some insight for further biomedical applications in efficient osteosarcoma therapy.

Construction of a nanofiber network within 3D printed scaffolds for vascularized bone regeneration.

Three-dimensional (3D) printed scaffolds provide a promising prospective for application in bone tissue engineering. 3D printed scaffolds with micro- and nano-fibrous structures that facilitate cell adhesion and migration, and combined vascularization and osteoinduction bioactivity will be ideal implants for bone defect repair. Here, we fabricated a 3D printed biodegradable poly (glycerol-co-sebacic acid-co-l-lactic acid-co-polyethylene glycol) (PGSLP)-based scaffold that was internally filled with gelatin nanofibers and allowed the local release of deferoxamine (DFO), which is essential for angiogenesis and osteogenesis in bone regeneration. The nanofibrous structured gelatin/PGSLP (NGP) scaffold was fabricated using a thermally induced phase separation (TIPS) technique, and the macroporous structured gelatin/PGSLP (MGP) scaffold was prepared by directly freeze-drying. The in vitro experiments demonstrated that both DFO-loaded NGP and DFO-loaded MGP scaffolds can promote the migration and tubular formation of human umbilical vein endothelial cells (HUVECs), and enhance the mineralized nodule formation and osteogenic-related gene expression during osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). In a rat critical-sized calvarial defect model, the results suggested that the scaffolds with DFO loading significantly promote the vascular formation and accelerate bone regeneration, while the enhancement of vascularization and osteogenesis in vivo in DFO-loaded NGP scaffold was better than that in DFO-loaded MGP scaffold. Therefore, the constructed PGLSP-based scaffolds with micro- and nano-fibrous structures would be promising candidates to match the structural and functional requirements for vascularized bone regeneration.

Tannic acid-reinforced methacrylated chitosan/methacrylated silk fibroin hydrogels with multifunctionality for accelerating wound healing.

Natural polymeric hydrogel featuring multifunctional properties is more attractive as wound dressing. Herein, Tannic acid (TA)-reinforced methacrylated chitosan (CSMA)/methacrylated silk fibroin (SFMA) hydrogels were fabricated by two-step method of photopolymerization and TA solution incubating treatment. The TA in hydrogels not only served as second crosslinker improving the mechanical performance of up to a 5-fold increase (5 % TA treatment) than the pristine one, but also as functional molecule that endowed the hydrogels with enhanced adhesiveness and antioxidative properties. Besides, the introduction of TA into hydrogels further improved the antimicrobial activities against both Escherichia coli (E. coli) and Staphylococcus Aureus (S. aureus), as well as the cytocompatibility on fibroblasts. Moreover, it was demonstrated that the TA-treated CSMA/SFMA hydrogels could significantly promote wound healing in a full-thickness skin defect model. Collectively, these results showed that TA-reinforced CSMA/SFMA hydrogels could be a promising candidate as wound dressing.