Microenvironment-responsive Cu-phenolic networks coated nanofibrous dressing with timely macrophage phenotype transition for chronic MRSA infected wound healing.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a pressing clinical issue that impedes wound healing. Pro-inflammatory M1 macrophages is required to clear bacteria and recruit various cell types during the initial phase of wound healing, but timing of this process is crucial. Herein, a microenvironment-responsive nanofibrous dressing capable of timely macrophage phenotype transition in vivo is constructed by coating copper ions (Cu2+)-polydopamine (PDA) networks on poly (ε-caprolactone) fiber (PCL-fiber) membrane. During the initial post-implantation period, the nanofibrous dressing show pH-sensitive Cu2+ release in the acidic infection microenvironment. The release Cu2+ have a direct killing effect on MRSA, and promote the proinflammatory M1 phenotype of macrophages to enhance the antibacterial macrophage response. Later, PDA to become a reactive oxygen species (ROS) scavenger when in microenvironments with elevated ROS levels, which conferred the dressing with an immunomodulatory activity that convert M1 macrophages into M2 macrophages. In vivo examination in an MRSA infected full-thickness skin wounds of rat model demonstrates that this dressing significantly facilitated infection eradication and wound healing through modulating local inflammatory phenotype. Overall, this study offers a simple and effective approach for timely manipulation of inflammation progression to promote infected wound healing.

Injectable temperature-sensitive hydrogel system incorporating deferoxamine-loaded microspheres promotes H-type blood vessel-related bone repair of a critical size femoral defect.

Insufficient vascularization is a major challenge in the repair of critical-sized bone defects. Deferoxamine (DFO) has been reported to play a potential role in promoting the formation of H-type blood vessels, a specialized vascular subtype with coupled angiogenesis and osteogenesis. However, whether DFO promotes the expression of H-type vessels in critical femoral defects with complete periosteal damage remains unknown. Moreover, stable drug loading systems need to be designed owing to the short half-life and high-dose toxic effects of DFO. In this study, we developed an injectable DFO-gelatin microspheres (GMs) hydrogel complex as a stable drug loading system for the treatment of critical femoral defects in rats. Our results showed that sustained release of DFO in critical femoral defects stimulated the generation of functional H-type vessels. The DFO-GMs hydrogel complex effectively promoted proliferation, formation, and migration of human umbilical vein endothelial cells in vitro. In vivo, the application of the DFO-GMs hydrogel complex expanded the distribution range and prolonged the expression time of H-type vessels in the defect area and was positively correlated with the number of osterix+ cells and new bone tissue. Topical application of the HIF-1α inhibitor PX-478 partially blocked the stimulation of H-type vessels by DFO, whereas the osteogenic potential of the latter was also weakened. Our results extended the local application of DFO and provided a theoretical basis for targeting H-type vessels to treat large femoral defects. STATEMENT OF SIGNIFICANCE: Abundant functional blood vessels are essential for bone repair. The H-type blood vessel is a functional subtype with angiogenesis and osteogenesis coupling potential. A drug loading system with long-term controlled release was first used to investigate the formation of H-type blood vessels in critical femoral defects and promotion of bone repair. Our results showed that the application of DFO-GMs hydrogel complex expanded the distribution range and expression time of H-type vessels, and was positively correlated with the number of osteoblasts and volume of new bone tissue. These results expanded the local application approach of DFO and provide a theoretical basis for targeting H-type vessels to treat large femoral defects.

Multifunctional PCL composite nanofibers reinforced with lignin and ZIF-8 for the treatment of bone defects.

Polycaprolactone (PCL) nanofibers have become an ideal material for bone tissue engineering due to a series of advantages. Considering the clinical treatment of bone defects, in addition to meeting the golden standard, PCL based nanofibers also need to be multifunctional to anti-inflammatory, antibacterial properties, and enhance the bone regeneration and repair. Herein, we successfully developed the multifunctional PCL/LIG/ZIF-8 composite nanofibers by loading ZIF-8 on electrospun PCL/lignin (PCL/LIG) nanofibers. The prepared composite nanofibers exhibit fairly good wettability and acceptable degradation rate, as well as excellent antioxidative stress and antibacterial properties originating from the incorporated LIG and loaded ZIF-8. Moreover, owing to the synergistic effect of LIG and ZIF-8, the composite nanofibers present excellent osteogenic differentiation, which can be verified in biomineralization experiments and real-time quantitative polymerase chain reaction. These results indicate that the PCL/LIG/ZIF-8 composite nanofibers, as potential healthcare candidate, have a promising applied in the treatment of bone defects.

Fabrication of Dexamethasone-Loaded Dual-Metal-Organic Frameworks on Polyetheretherketone Implants with Bacteriostasis and Angiogenesis Properties for Promoting Bone Regeneration.

Polyetheretherketone (PEEK) is a biocompatible polymer, but its clinical application is largely limited due to its inert surface. To solve this problem, a multifunctional PEEK implant is urgently fabricated. In this work, a dual-metal-organic framework (Zn-Mg-MOF74) coating is bonded to PEEK using a mussel-inspired polydopamine interlayer to prepare the coating, and then, dexamethasone (DEX) is loaded on the coating surface. The PEEK surface with the multifunctional coating provides superior hydrophilicity and favorable stability and forms an alkaline microenvironment when Mg2+, Zn2+, 2,5-dihydroxyterephthalic acid, and DEX are released due to the coating degradation. In vitro results showed that the multifunctional coating has strong antibacterial ability against both Escherichia coli and Staphylococcus aureus; it also improves human umbilical vein endothelial cell angiogenic ability and enhances rat bone marrow mesenchymal stem cell osteogenic differentiation activity. Furthermore, the in vivo rat subcutaneous infection model, chicken chorioallantoic membrane model, and rat femoral drilling model verify that the PEEK implant coated with the multifunctional coating has strong antibacterial and angiogenic ability and promotes the formation of new bone around the implant with a stronger bone-implant interface. Our findings indicate that DEX loaded on the Zn-Mg-MOF74 coating-modified PEEK implant with bacteriostasis, angiogenesis, and osteogenesis properties has great clinical application potential as bone graft materials.

Direct deposition of two-dimensional MXene nanosheets on commercially available filter for fast and efficient dye removal.

Generally, the efficiency of water purification can be greatly increased by a high-flux membrane separation technology. One major challenge in the application of this technology is to achieve high removal efficacy of target pollutants with elevated water flux. Here we report a novel self-assembled composite by depositing two-dimensional MXene nanosheets on a commercialized mixed cellulose ester filter (as designated as MCM). Morphology study reveals that MCM exhibits an ultrathin flaked structure with uniform nanochannels which is stapled on a porous support. The tailored membrane has been successfully applied in the methylene blue solution treatment and 100% ± 0.1% removal rate is achieved while the feed concentration of dye solution is up to 90 mg·L-1. Concurrently, stable and comparatively elevated water flux was achieved, i.e., 28.94 ± 0.74 L·m-2·h-1, which is 1.88-fold of that of the commercialized UTC60 membrane. Further investigations on the separation mechanism are performed to get more insights into separation performance exhibited by MCM. It is found that the size-selective sieving, electrostatic repulsion of MXene and the high porosity of substrate play the synergistic effect on the fast and efficient dye removal behavior. Taken together, the composite membrane fabricated in present work provides an alternatively high-efficiency approach for dye treatment, and unflagging efforts will be further invested on the development and large-scale application of MXene-based membrane.

High Performance Attapulgite/Polypyrrole Nanocomposite Reinforced Polystyrene (PS) Foam Based on Supercritical CO2 Foaming.

CO2 has been regarded as one of the most promising blowing agents for polystyrene (PS) foam due to its non-flammability, low price, nontoxicity, and eco-friendliness. However, the low solubility and fast diffusivity of CO2 in PS hinder its potential applications. In this study, an attapulgite (ATP)/polypyrrole (PPy) nanocomposite was developed using the in situ polymerization method to generate the hierarchical cell texture for the PS foam based on the supercritical CO2 foaming. The results demonstrated that the nanocomposite could act as an efficient CO2 capturer enabling the random release of it during the foaming process. In contrast to the pure PS foam, the ATP/PPy nanocomposite reinforced PS foam is endowed with high cell density (up to 1.9 × 106) and similar thermal conductivity as the neat PS foam, as well as high compression modulus. Therefore, the in situ polymerized ATP/PPy nanocomposite makes supercritical CO2 foaming desired candidate to replace the widely used fluorocarbons and chlorofluorocarbons as PS blowing agents.