Near-Infrared Fluorescent Silica Nanoparticles Based on Gold-Silver Alloy Nanoclusters for Clinical Diagnosis.

In clinical diagnosis, fluorescent particles are applied to detect analytes in biofluids, such as blood and saliva. However, current fluorescence detection methods have not been optimized to account for the overlapping autofluorescence peaks of biological substances. Gold and silver nanoclusters are known to the novel fluorescent materials and their emission wavelengths depend on cluster size. In this study, we developed fluorescent silica nanoparticles using gold-silver alloy nanoclusters and chitosan (CS) (NH2-SiO2@Au@CS@AuAg) by the layer-by-layer method. Under UV-light irradiation at 365 nm, the emission wavelength of NH2-SiO2@Au@CS@AuAg reached 750 nm in the near-IR region. Scanning electron microscopy images revealed that the shape of NH2-SiO2@Au@CS@AuAg was uniform and spherical. The fluorescence spectrum of horse blood obtained in the presence of NH2-SiO2@Au@CS@AuAg contained a specific fluorescence peak attributed to NH2-SiO2@Au@CS@AuAg, which was distinguishable from the autofluorescence peaks. These results showed that NH2-SiO2@Au@CS@AuAg has advantageous fluorescence properties for clinical diagnostic applications.

Magnetic Polystyrene Nanoparticles Prepared by Emulsion Solvent-Evaporation for the Chemiluminescent Immunoassay.

In clinical diagnosis, magnetic polystyrene nanoparticles (MPS NPs) are commonly applied to, e.g., the chemiluminescent immunoassay (CLEIA). However, the conventional preparation method of MPS NPs requires a long duration of heating to form polymer particles, which is inefficient. In this study, we prepared MPS NPs by emulsion solvent-evaporation without heating. We evaluated the effect of the solvent in the water and organic phases on the magnetic particle content. MPS NPs prepared by 4% (v/v) MeOH aqueous solution and adding stearic acid (SA) (4MeSA-MPS NPs) exhibited the highest magnetic particle content. Furthermore, CLEIA analysis indicates that the C-reactive protein detection limit is 80 pg/mL. Thus, 4MeSA-MPS NPs are promising for clinical diagnoses.

Gold Coating of Silver Nanoplates for Enhanced Dispersion Stability and Efficient Antimicrobial Activity against Intracellular Bacteria.

Silver nanoparticles have antibacterial activity. However, the nanoparticles are unstable and easily form aggregates, which decreases their antibacterial activity. To improve the dispersion stability of silver nanoparticles in aqueous media and to increase their effectiveness as antibacterial agents, we coated triangular plate-like silver nanoparticles (silver nanoplates, Ag NPLs) with one or two layers of gold atoms (Ag@Au1L NPLs and Ag@Au2L NPLs, respectively). These gold coatings improved the dispersion stability in aqueous media with high salt concentrations. Ag@Au1L NPLs showed stronger antibacterial activity on pathogenic bacteria than Ag NPLs and Ag@Au2L NPLs. Furthermore, the Ag@Au1L NPLs decreased the number of bacteria in RAW 264.7 cells. The Ag@Au1L NPLs displayed no cytotoxicity towards RAW 264.7 cells and could be used as antibacterial agents for intracellular bacterial infections.

Hotmelt tissue adhesive with supramolecularly-controlled sol-gel transition for preventing postoperative abdominal adhesion.

Postoperative adhesion is a serious and frequent complication, but there is currently no reliable anti-adhesive barrier available due to low tissue adhesiveness, undesirable chemical reactions, and poor operability. To overcome these problems, we report a single-syringe hotmelt tissue adhesive that dissolves upon warming over 40 °C and coheres at 37 °C as a postoperative barrier. Tendon-derived gelatin was conjugated with the ureidopyrimidinone unit to supramolecularly control the sol-gel transition behavior. This functionalization improved bulk mechanical strength, tissue-adhesive properties, and stability under physiological conditions through the augmentation of intermolecular hydrogen bonding by ureidopyrimidinone unit. This biocompatible adhesive prevented postoperative adhesion between cecum and abdominal wall in adhesion models of rats. This hotmelt tissue adhesive has enormous potential to prevent postoperative complications and may contribute to minimally invasive surgery. STATEMENT OF SIGNIFICANCE: There is a strong need to develop medical tissue adhesives with high biocompatibility, tissue adhesiveness, and operatability to prevent postoperative complications. In this report, single syringe, hotmelt-type tissue adhesive was developed by controlling sol-gel transition behavior of gelatin through supramolecular approach. The functionalization of gelatin with quadruple hydrogen bonding improved key features necessary for anti-adhesive barrier including bulk mechanical strength, tissue adhesive property, stability under physiological conditions, and anti-adhesive property. The hotmelt tissue adhesive can be used for a sealant, hemostatic reagent, and wound dressing to prevent postoperative complications including delayed bleeding, perforation, and inflammation and contribute to minimally invasive surgery.

Prevention of postoperative adhesion with a colloidal gel based on decyl group-modified Alaska pollock gelatin microparticles.

Postoperative adhesion, bonding of the abdominal wall to damaged organs, causes severe complications after abdominal surgery. Despite the availability of physical barriers (i.e., solutions, films, and hydrogels), adhesion prevention materials that are a single-substance system with stability in wet tissue and ease of use have not been reported. Here, we report a microparticle based, sprayable adhesion prevention material comprising decyl group modified Alaska pollock gelatin (C10-ApGltn). C10-ApGltn microparticles (C10-MPs) were prepared by a coacervation method, freeze drying, and thermal crosslinking. The C10-MPs adhered to and formed a colloidal gel layer on intestinal serosal tissue by hydration without any crosslinking agents. After hydration of the C10-MPs, the resulting colloidal gel layer did not adhere to other tissues. Additionally, the C10-MP colloidal gel layer formed on the stomach serosal tissue showed stability when submersed in saline for 2 days. The colloidal gel layer also showed tissue followability. An in vivo rat adhesion model revealed that C10-MP colloidal gel layer on the cecum and abdominal wall defects effectively reduced postoperative adhesion and induced tissue remodeling, including re-mesothelialization. Therefore, C10-MPs are a potential anti-adhesion material for preventing postoperative adhesion. STATEMENT OF SIGNIFICANCE: We evaluated the postoperative adhesion prevention ability of a colloidal gel based on decyl group modified Alaska pollock gelatin (ApGltn) microparticles (C10-MPs). These microparticles are sprayable and form a colloidal gel with only hydration on the gastrointestinal tissue. We revealed that the modification of the decyl group into ApGltn improved the stability of C10-MP colloidal gel on the tissue by hydrophobic interaction in the in-vitro experiments. The gel prevented postoperative adhesion by being a physical barrier in the in-vivo rat adhesion model.

Enhanced burst strength of catechol groups-modified Alaska pollock-derived gelatin-based surgical adhesive.

Aortic anastomotic leak is a potentially fatal complication that can occur after treatment of aortic dissection or aneurysm. Several surgical adhesives have been used to prevent this complication, but all have problems with regard to tissue adhesion or biocompatibility. In the present study, we developed a surgical adhesive composed of boric acid-protected catechol groups-modified Alaska pollock-derived gelatin (Cat-ApGltn) and a poly(ethylene glycol)-based crosslinker (4S-PEG). By avoiding oxidation of catechol groups using boric acid, resulting Cat-ApGltn adhesive formed a strong hydrogel by double crosslinking: chemical crosslinking by 4S-PEG, and chemical and physical crosslinking by the catechol groups. The catechol groups modification contributed to increased bulk strength and decreased gelation time/swelling ratios. The Cat-ApGltn adhesive, in which 7.8 mol% of the amino groups of the original ApGltn (Org-ApGltn) were modified with catechol groups, demonstrated 2.3 times higher burst strength compared with the Org-ApGltn adhesive, and 3.9 times higher burst strength compared with a commercial fibrin adhesive. When the Cat-ApGltn adhesive was implanted subcutaneously into rats, it induced only weak inflammation similar to that induced by the Org-ApGltn adhesive, and was completely degraded within 2 months. Therefore, the Cat-ApGltn adhesive has great potential for use in the field of cardiovascular surgery.

Improved tissue adhesion property of a hydrophobically modified Alaska pollock derived gelatin sheet by UV treatment.

Tissue adhesives have been developed for sealing tissue damaged in surgery. Among these, sheet-type adhesives require a relatively long time to adhere to biological tissue under wet conditions. To address this clinical problem, we fabricated a tissue-adhesive fiber sheet (AdFS) based on decanyl group (C10) modified Alaska pollock-derived gelatin (C10-ApGltn) using electrospinning. Ultraviolet (UV) irradiation of the AdFS was performed to increase the affinity between the AdFS and wet biological tissue by introducing hydrophilic functional groups. The UV irradiated AdFS (UV-C10-AdFS) strongly adhered to porcine pleura within 2 min under wet conditions and showed higher burst strength compared with the original ApGltn (Org-ApGltn) sheet. Hematoxylin-eosin stained sections revealed that a dense UV-C10-AdFS layer remained on the surface of the porcine pleura even after burst strength measurement. Moreover, UV-C10-AdFS has excellent cytocompatibility and efficiently supports the growth of L929 cells. UV-C10-AdFS is a promising adhesive material for sealing wet biological tissue.

Correction: Prevention of pulmonary air leaks using a biodegradable tissue-adhesive fiber sheet based on Alaska pollock gelatin modified with decanyl groups.

Correction for 'Prevention of pulmonary air leaks using a biodegradable tissue-adhesive fiber sheet based on Alaska pollock gelatin modified with decanyl groups' by Hiroaki Ichimaru et al., Biomater. Sci., 2021, DOI: 10.1039/d0bm01302a.

Prevention of pulmonary air leaks using a biodegradable tissue-adhesive fiber sheet based on Alaska pollock gelatin modified with decanyl groups.

Tissue adhesives have been widely used in surgery to treat pulmonary air leaks. However, conventional adhesives have poor interfacial strength under wet conditions. To overcome this clinical problem, we modified Alaska pollock-derived gelatin to include decanyl (C10) groups (C10-ApGltn) and used electrospinning to create a tissue-adhesive fiber sheet (AdFS). C10-AdFS showed higher burst strength when adhering to porcine pleura compared with a sheet of original ApGltn (Org-ApGltn). Hematoxylin-eosin-stained sections after burst experiments reveal that a dense C10-AdFS layer remained on the surface of the porcine pleura. The effect of the degree of C10 modification of ApGltn on the burst strength was evaluated. ApGltn with a C10 modification ratio of 13 mol% amino groups (13C10-AdFS) exhibited the highest burst strength. Furthermore, from ex vivo experiments with extracted rat lung, 13C10-AdFS exhibited a higher burst strength (41 cm H2O) than Org-AdFS. The decanyl groups in 13C10-AdFS interacted with the hydrophobic proteins and the lipid bilayers of the cells, resulting in the high interfacial strength between 13C10-AdFS and the pleura. Moreover, 13C10-AdFS samples implanted subcutaneously in the backs of rats were completely degraded within 21 days without any severe inflammation. These results show that 13C10-AdFS is a promising adhesive material for the treatment of pulmonary air leaks.

Effects of pulsed laser irradiation on gold-coated silver nanoplates and their antibacterial activity.

Gold-coated silver nanoplates, when subjected to pulsed laser irradiation, changed their shape from triangular to spherical, accompanied by a shift of their extinction spectra. The simple single crystal structure of the silver nanoplates changed to multiple small crystal domains. The ratio of silver to gold of the particles also changed from 22 : 1 to 4.5 : 1, enabling more silver to be released. As a result, the antibacterial activity of the gold-coated silver nanoplates was significantly increased after pulsed laser irradiation.