Toxin-Enabled "On-Demand" Liposomes for Enhanced Phototherapy to Treat and Protect against Methicillin-Resistant Staphylococcus aureus Infection.

An effective therapeutic strategy against methicillin-resistant Staphylococcus aureus (MRSA) that does not promote further drug resistance is highly desirable. While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off-target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore-forming toxins trigger on-demand payload release. Upon subsequent near-infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on-demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high-priority pathogens.

Preparation of cellulose-based flexible SERS and its application for rapid and ultra-sensitive detection of thiram on fruits and vegetables.

In response to the prevalent issue of thiram as a common pesticide residue on the surface of fruits and vegetables, our research team employed an acidic hydrated metal salt low co-fusion solvent to dissolve cellulose lysis slurry. Subsequently, a regenerated cellulose membrane (RCM) was successfully prepared via sol-gel method. Uniformly sized Ag nanoparticles (NPs) were deposited on RCM utilizing the continuous ion layer adsorption and reaction (SILAR) technique. The resulting Ag NPs/RCM flexible surface-enhanced Raman spectroscopy (SERS) substrates exhibited a minimum detection limit of 5 × 10-9 M for Rhodamine 6G (R6G), demonstrating good uniformity (RSD = 4.86 %) and reproducibility (RSD = 3.07 %). Moreover, the substrate displayed a remarkable sensitivity of 10-10 M toward thiram standard solution. Given its inherent flexibility, the substrate proves advantageous for the detection of three-dimensional environments such as fruit and vegetable surfaces, and its practicality has been confirmed in the detection of thiram residue on apples, tomatoes, pears, and other fruits and vegetables.

Bacterial cellulose loaded with silver nanoparticles as a flexible, stable and sensitive SERS-active substrate for detection of the shellfish toxin DTX-1.

Diarrheal shellfish toxins are considered one of the most lethal red tide algae toxins in the worldwide. In this work, we propose an Ag NPs-loaded bacterial cellulose membrane (BCM) surface-enhanced Raman scattering (SERS) sensor based on an aptamer (Apt) for the ultrasensitive detection of dinophysistoxin (DTX-1), a type of diarrheal shellfish toxin. During drying, Ag NPs can be further densified on "gel-like" BCM to form high-density SERS "hot spots". We developed the "Apt-SH@Ag NPs@BCM" SERS sensor and used the competition of DTX-1 and complementary base (Cob) in the process of base complementary pairing to achieve SERS detection of DTX-1, with a minimum detection limit of 9.5 × 10-10 mol/L. Sample assays showed DTX-1 recovery rates ranging from 95.8% and 108.2% and the detection results were comparable to those obtained by LC-MS. Therefore, this work holds great potential for detecting of toxic substances in shellfish products, especially for the oyster (portuguese oyster) and mussel (blue mussel).

In situ forming hydrogel recombination with tissue adhesion and antibacterial property for tissue adhesive.

In situ forming hydrogels with strong adhesive strength and antibacterial activity are of great interest to serve as tissue adhesive in fields like wound dressing and mass hemorrhage. In this study, hybrid hydrogel (GOHA) based on gelatin and oxidized hyaluronic acid was developed and endowed with excellent mechanical strength and tissue adhesion. According to our results, GOHA hydrogel exhibits a fast gelation time of around 60 s, robust compression strength of 223.43 ± 24.28 kPa, and strong adhesion of 14.33 ± 0.78 kPa to porcine skin, which is much higher than that of commercial fibrin glue (around 1.00 kPa). Meanwhile, through the loading of levofloxacin, obvious antibacterial activity can be obtained for wider applications. Notably, it would not compromise the hemocompatibility and cytocompatibility in vitro. In summary, this kind of hybrid hydrogel shows great potential as tissue adhesive in biomedical fields.

Multi-Crosslinked Hydrogels with Instant Self-Healing and Tissue Adhesive Properties for Biomedical Applications.

Due to the defects like long gelling time, inferior mechanical properties and weak adhesion, in situ forming hydrogels are still restricted in biomedical applications like viscera rupture and targeted therapy. To address these problems, a new kind of multi-crosslinked hydrogel (G-OKG-DA) consisting of gelatin, oxidized konjac glucomannan (OKG), and dopamine (DA) is proposed in this study. The resulting hybrid hydrogel is endowed with a short gelling time (≈3 min) and injectable capacity. According to the mechanical and adhesive tests, G-OKG-DA hydrogel shows a robust tensile strength of 23.94 kPa, as well as a higher adhesive strength (≈150 kPa) than commercial fibrin glue. In addition, an instant self-healing behavior of G-OKG-DA hydrogel can be found, which is attributed to multi-cross-linking reactions including Schiff-based dynamic covalent bonds between OKG and gelatin, oxidative polymerization of DA, and catechol-mediated chemistry like Michael addition and DA-quinone coupling. Importantly, the multi-crosslinked hydrogel will not compromise its hemocompatibility and cytocompatibility in vitro, suggesting potential applications in biomedical fields as tissue adhesive and implants.

Intervention effects of multilayer core-shell particles on colitis amelioration mechanisms of capsaicin.

The intervention effects of delivery systems on the digestion and adsorption profiles and, thus, the pharmacological effects of bioactive compounds represent an intriguing scientific hypothesis that can be proven with research case studies. Delivery systems with tailor-made structures fabricating from the same building materials offer a new research strategy for deciphering the modulating effects of the digestive fate on the therapeutic efficacy of encapsulated bioactive compounds. Herein, we developed capsaicin-loaded core-shell nanoparticles (Cap NPs), microparticles (Cap MPs) and nano-in-micro particles (Cap NPs in MPs) and investigated their regulatory effects on the digestive fate and colitis-alleviating mechanisms of capsaicin. Results suggested that the small intestine dominant absorption of Cap NPs differed significantly with the colorectal dominated accumulation of Cap MPs and Cap NPs in MPs in terms of the colitis alleviating mechanisms. Cap NPs alleviated colitis mainly through promoting the colonization of short-chain fatty acid-producing bacteria, maintaining intestinal barrier homeostasis and partially inhibiting the activation of the NF-κB pro-inflammatory pathway. Whereas, better dietary intervention effects were achieved from Cap NPs in MPs via promoting the proliferation of mucus-related bacteria and enhanced triggering efficiency on the TRPV1-mucus-microbiotas cyclic cascade. This work confirmed that rationally designed biomaterial-based delivery vehicles can flexibly interfere with the therapeutic mechanisms of encapsulated cargos, representing a new horizon in the field of precise nutrition.

Nanofibrous tissue engineering scaffold with nonlinear elasticity created by controlled curvature and porosity.

Micro-crimped fibers have been widely used in the field of tissue repair to mimic the natural tissue structure and mechanical properties. However, the electrospun nanofibrous membrane is a kind of dense structure, which cannot meet the requirements of mechanical properties and permeability. In this study, we prepared nanofibrous scaffold with controllable porosity and crimpness by sacrificing fiber components and releasing residual stress. The results show that the crimpness of the fiber is positively related to the porosity, and with the increase of porosity, the fiber crimpness increases greatly. Meanwhile, the scaffold modulus was reduced by 86% and the elongation at break doubled, which is similar to natural blood vessels. Moreover, it is found that the porous micro-crimped fiber scaffold promotes the adhesion and diffusion of endothelial cells, and facilitates the rapid endothelialization of the scaffold, which has a great potential for practical application.

Preparation of gelatin-based hydrogels with tunable mechanical properties and modulation on cell-matrix interactions.

Natural polymer material-based hydrogels normally show inferior mechanical stability and strength to bear large deformation and cyclic loading, therefore their applications in food, biomedical and tissue engineering fields are greatly limited. In this study, gelatin-based hydrogels with remarkable stability, as well as tunable mechanical properties, were prepared via a facile method known as the Hofmeister effect. The higher concentration of potassium sulfatesolution resulted in more dehydration and molecular chain folding, thus the treated hydrogels showed significantly improved tensile and compressive modulus, and decreased equilibrium swelling ratio, as revealed by scanning electron microscopy (SEM), Fourier transform infraredspectroscopy (FTIR), and mechanical tests, etc. Additionally, the reinforced hydrogels were recoverable and biocompatible to modulate the proliferation behavior of human umbilical vein endothelial cells. In conclusion, this paper provides a facile reference for tuning mechanical properties of gelatin-based hydrogels and cell-hydrogel interactions, which show potential capacity in tissue engineering and biomedical fields.

Endothelial Cell Migration Regulated by Surface Topography of Poly(ε-caprolactone) Nanofibers.

The study of cell migration on biomaterials is of great significance in tissue engineering and regenerative medicine. In recent years, there has been increasing evidence that the physical properties of the extracellular matrix (ECM), such as surface topography, affect various cellular behaviors such as proliferation, adhesion, and migration. However, the biological mechanism of surface topography influencing cellular behavior is still unclear. In this study, we prepared polycaprolactone (PCL) fibrous materials with different surface microstructures by solvent casting, electrospinning, and self-induced crystallization. The corresponding topographical structure obtained is a two-dimensional (2D) flat surface, 2.5-dimensional (2.5D) fibers, and three-dimensional (3D) fibers with a multilevel microstructure. We then investigated the effects of the complex topographical structure on endothelial cell migration. Our study demonstrates that cells can sense the changes of micro- and nanomorphology on the surface of materials, adapt to the physical environment through biochemical reactions, and regulate actin polymerization and directional migration through Rac1 and Cdc42. The cells on the nanofibers are elongated spindles, and the positive feedback of cell adhesion and actin polymerization along the fiber direction makes the plasma membrane continue to protrude, promoting cell polarization and directional migration. This study might provide new insights into the biomaterial design, especially those used for artificial vascular grafts.

Polymer-Infiltrated Nanoparticle Films Using Capillarity-Based Techniques: Toward Multifunctional Coatings and Membranes.

Polymer-infiltrated nanoparticle films (PINFs) are a new class of nanocomposites that offer synergistic properties and functionality derived from unusually high fractions of nanomaterials. Recently, two versatile techniques,capillary rise infiltration (CaRI) and solvent-driven infiltration of polymer (SIP), have been introduced that exploit capillary forces in films of densely packed nanoparticles. In CaRI, a highly loaded PINF is produced by thermally induced wicking of polymer melt into the nanoparticle packing pores. In SIP, exposure of a polymer-nanoparticle bilayer to solvent vapor atmosphere induces capillary condensation of solvent in the pores of nanoparticle packing, leading to infiltration of polymer into the solvent-filled pores. CaRI/SIP PINFs show superior properties compared with polymer nanocomposite films made using traditional methods, including superb mechanical properties, thermal stability, heat transfer, and optical properties. This review discusses fundamental aspects of the infiltration process and highlights potential applications in separations, structural coatings, and polymer upcycling-a process to convert polymer wastes into useful chemicals.