Designing a Hypoxia-Activated Sensing Platform Using an Azo Group-Triggered Reaction with the Formation of Silicon Nanoparticles.

Hypoxia is known as a specific signal of various diseases, such as liver fibrosis. We designed a hypoxia-sensitive fluorometric approach that cleaved the azo bond (N═N) in the presence of hypoxia-controlled agents (sodium dithionite and azoreductase). 4-(2-Pyridylazo) resorcinol (Py-N═N-RC) bears a desirable hypoxia-responsive linker (N═N), and its azo bond breakup can only occur in the presence of sodium dithionite and azoreductase and leads to the release of 2,4-dihydroxyaniline, which can react with 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane to generate yellow fluorescent silicon nanoparticles. This approach exhibited high selectivity and sensitivity toward both sodium dithionite and azoreductase over other potential interferences. The mouse liver microsome, which is known to contain azoreductase, was applied and confirmed the feasibility of the designed platform. Py-N═N-RC is expected to be a practical substrate for hypoxia-related biological analyses. Furthermore, silicon nanoparticles were successfully applied for Hela cell imaging owing to their negligible cytotoxicity and superb biocompatibility.

Surface-Confined Piezocatalysis Inspired by ROS Generation of Mitochondria Respiratory Chain for Ultrasound-Driven Noninvasive Elimination of Implant Infection.

Implant-associated infections (IAI) are great challenges to medical healthcare and human wellness, yet current clinical treatments are limited to the use of antibiotics and physical removal of infected tissue or the implant. Inspired by the protein/membrane complex structure and its generation of reactive oxygen species in the mitochondria respiration process of immune cells during bacteria invasion, we herein propose a metal/piezoelectric nanostructure embedded on the polymer implant surface to achieve efficient piezocatalysis for combating IAI. The piezoelectricity-enabled local electron discharge and the induced oxidative stress generated at the implant-bacteria interface can efficiently inhibit the activity of the attachedStaphylococcus aureusby cell membrane disruption and sugar energy exhaustion, possess high biocompatibility, and eliminate the subcutaneous infection by simply applying the ultrasound stimulation. For further demonstration, the treatment of root canal reinfection with simplified procedures has been achieved by using piezoelectric gutta-percha implanted in ex vivo human teeth. This surface-confined piezocatalysis antibacterial strategy, which takes advantage of the limited infection interspace, easiness of polymer processing, and noninvasiveness of sonodynamic therapy, has potential applications in IAI treatment.

Metal Phenolic Nanodressing of Porous Polymer Scaffolds for Enhanced Bone Regeneration via Interfacial Gating Growth Factor Release and Stem Cell Differentiation.

Porous polymer scaffolds are essential materials for tissue engineering because they can be easily processed to deliver stem cells or bioactive factors. However, scaffolds made of synthetic polymers normally lack a bioactive cell-material interface and undergo a burst release of growth factors, which may hinder their further application in tissue engineering. In this paper, a metal-phenolic network (MPN) was interfacially constructed on the pore surface of a porous poly(dl-lactide) (PPLA) scaffold. Based on the molecular gating property of the MPN supramolecular structure, the PPLA@MPN scaffold achieved the sustained release of the loaded molecules. In addition, the MPN coating provided a bioactive interface, thus encouraging the migration and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The PPLA@MPN scaffolds exhibited enhanced bone regeneration in a rat femoral defect model in vivo compared to PPLA, which is ascribed to the combined effect of sustained bone morphogenetic protein-2 (BMP-2) release and the osteogenic ability of MPN. This nanodressing technique provides a viable and straightforward strategy for enhancing the performance of porous polymer scaffolds in bone tissue engineering.

Microencapsulation of Ionic Liquid by Interfacial Self-Assembly of Metal-Phenolic Network for Efficient Gastric Absorption of Oral Drug Delivery.

Improving bioavailability of orally delivered drugs is still challenging, as conventional drug delivery systems suffer from non-specific drug delivery in the gastrointestinal (GI) tract and limited drug absorption efficiency. Gastric drug delivery is even more difficult due to the harsh microenvironment, short retention time, and physiologic barriers in the stomach. Here, an oral drug delivery microcapsule system was developed for gastric drug delivery, which consists of ionic liquid (IL) as the inner carrier and metal-phenolic network (MPN) as the microcapsule shell. The IL@MPN microcapsules are prepared by interfacial self-assembly of FeIII and quercetin at the interface of hydrophobic IL ([EMIM][NTf2]) and water. The formation of MPN shell could improve the stability of IL droplets in water and endow the system with pH-response drug release properties, while the encapsulated IL core could efficiently load the drug and enhance the drug tissue permeability. The IL@MPN microcapsules showed enhanced drug absorption in the stomach after oral administration in a rat model, where the microcapsules are disassembled in gastric acid, and the released IL could reduce the viscosity of mucus gel and increase the drug transport rate across endothelial cells. This work presents a simple yet efficient strategy for oral drug delivery to the stomach. Given the diversity and versatility of both MPN and IL, the proposed self-assembled microcapsules could expand the toolbox of drug delivery systems with enhanced oral drug bioavailability.

Stem cell microencapsulation maintains stemness in inflammatory microenvironment.

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with FeIII/tannic acid coordination network to obtain spheroid@[FeIII-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.

Metal-phenolic network coatings for engineering bioactive interfaces.

The surface modification of biomaterials is crucial for constructing bioactive interfaces capable of interacting with specific biomolecules, controlling cell behavior and regulating biological processes. Because of their excellent biocompatibility, facile preparation, pH-responsiveness and universal adhesion, surface coatings made from metal-phenolic network (MPN) have attracted extensive attention for handling interfacial properties and designing biomaterials in recent years. Different methods and technologies for assembling MPN coatings are summarized and compared in this paper, followed by highlighting the advantages of MPN coatings as bioactive interfaces for controlling biological process at the molecular, cellular, and tissue levels. Current challenges and prospects of MPN coatings for biomedical applications are also discussed.