Polyphenol-Enabled 2D Nanopatch for Enhanced Nasal Mucoadhesion and Immune Activation.

The advancement of effective nasal mucoadhesive delivery faces challenges due to rapid mucociliary clearance (MCC). Conventional studies have employed mucoadhesive materials, mainly forming spherical nanoparticles, but these offer limited adhesion to the nasal mucosa. This study hypothesizes that a 2D nanoscale structure utilizing adhesive polyphenols can provide a superior strategy for countering MCC, aligning with the planar mucosal layers. We explore the use of tannic acid (TA), a polyphenolic molecule known for its adhesive properties and ability to form complexes with biomolecules. Our study introduces an unprecedented 2D nanopatch, assembled through the interaction of TA with green fluorescent protein (GFP), and cell-penetrating peptide (CPP). This 2D nanopatch demonstrates robust adhesion to nasal mucosa and significantly enhances immunoglobulin A secretions, suggesting its potential for enhancing nasal vaccine delivery. The promise of a polyphenol-enabled adhesive 2D nanopatch signifies a pivotal shift from conventional spherical nanoparticles, opening new pathways for delivery strategies through respiratory mucoadhesion.

Red Fluorescence from Organic Microdots: Leveraging Foldamer-Linked Azobenzene for Enhanced Stability and Intensity in Bioimaging Applications.

Azobenzene, while relevant, has faced constraints in biological system applications due to its suboptimal quantum yield and short-wavelength emission. This study presents a pioneering strategy for fabricating organic microdots by coupling foldamer-linked azobenzene, resulting in robust fluorescence intensity and stability, especially in aggregated states, thereby showing promise for bioimaging applications. Comprehensive experimental and computational examinations elucidate the mechanisms underpinning enhanced photostability and fluorescence efficacy. In vitro and in vivo evaluations disclose that the external layer of cis-azo-foldamer microdots performs a self-sacrificial function during photo-bleaching. Consequently, these red-fluorescent microdots demonstrate extraordinary structural and photochemical stabilities over extended periods. The conjugation of a ß-peptide foldamer to the azobenzene chromophore through a glycine linker instigates a blue-shifted and amplified π*-n transition. Molecular dynamics simulations reveal that the aggregated state of cis-azo-foldamers fortifies the stability of cis isomers, thereby augmenting fluorescence efficiency. This investigation furnishes crucial insights into conceptualizing novel, biologically inspired materials, promising stable and enduring imaging applications, and carries implications for diverse arenas such as medical diagnostics, drug delivery, and sensing technologies.

Simultaneous coupling of metal removal and visual detection by nature-inspired polyphenol-amine surface chemistry.

The interplay between polyphenols, amines, and metals has broad implications for surface chemistry, biomaterials, energy storage, and environmental science. Traditionally, polyphenol-amine combinations have been recognized for their ability to form adhesive, material-independent thin layers that offer a diverse range of surface functionalities. Herein, we demonstrate that a coating of tannic acid (TA) and polyethyleneimine (PEI) provides an efficient platform for capturing and monitoring metal ions in water. A unique feature of our PEI/TA-coated microbeads is the 'Detection-Capture' (Detec-Ture) mechanism. The galloyl groups in TA coordinate with Fe(III) ions (capture), initiating their oxidation to gallol-quinone. These oxidized groups subsequently react with PEI amines, leading to the formation of an Fe(II/III)-gallol-PEI network that produces a vivid purple color, thereby enabling visual detection. This mechanism couples metal capture directly with detection, distinguishing our approach from existing studies, which have either solely focused on metal removal or metal detection. The metal capturing capacity of our materials stands at 0.55 mg g-1, comparable to that of established materials like alginate and wollastonite. The detection sensitivity reaches down to 0.5 ppm. Our findings introduce a novel approach to the utility of metal-polyphenol-amine networks, presenting a new class of materials suited for simultaneous metal ion detection and capture in environmental applications.

Enhancing the production of adeno-associated virus (AAV)2 and AAV9 with high full capsid ratio in HEK293 cells through design-of-experiment optimization of triple plasmid ratio.

The recombinant adeno-associated virus (rAAV) vectors used in gene therapy are usually produced by transfecting three different plasmids (Adenoviral helper plasmid (pHelper), AAV rep/cap plasmids (pRepCap), and Transgene plasmid (pAAV-GOI)) into human embryonic kidney 293 (HEK293) cells. However, the high proportion of unwanted empty capsids generated during rAAV production is problematic. To simultaneously enhance the genome titer and full capsid ratio, the ratio of the three plasmids transfected into HEK293 cells was optimized using design-of-experiment (DoE). AAV2 and AAV9, which have different production kinetics, were selected as cell-associated and secreted model AAVs, respectively. In 125 mL Erlenmeyer flasks, the genome titers of rAAV2 and rAAV9 at DoE-optimized plasmid weight ratios (pHelper:pRep2Cap2:pAAV-GOI = 1:3.52:0.50 for rAAV2 and pHelper:pRep2Cap9:pAAV-GOI = 1:1.44:0.27 for rAAV9) were 2.23-fold and 2.26-fold higher than those in the widely used plasmid weight ratio (1:1:1), respectively. In addition, compared with the plasmid ratio of 1:1:1, the relative VP3 band intensities of rAAV2 and rAAV9, which represent the relative empty capsid ratios, were reduced by 26% and 25%, respectively, at the DoE-optimized plasmid ratio. Reduced empty capsid ratios in the DoE-optimized plasmid ratios were also confirmed using transmission electron microscopy (TEM). Taken together, regardless of the AAV serotype, DoE-aided optimization of the triple plasmid ratio was found to be an efficient means of improving the production of rAAV with a high full capsid ratio.

Coagulant Protein-Free Blood Coagulation Using Catechol-Conjugated Adhesive Chitosan/Gelatin Double Layer.

Since the discovery of polyphenolic underwater adhesion in marine mussels, researchers strive to emulate this natural phenomenon in the development of adhesive hemostatic materials. In this study, bio-inspired hemostatic materials that lead to pseudo-active blood coagulation, utilizing traditionally passive polymer matrices of chitosan and gelatin are developed. The two-layer configuration, consisting of a thin, blood-clotting catechol-conjugated chitosan (CHI-C) layer and a thick, barrier-functioning gelatin (Geln) ad-layer, maximizes hemostatic capability and usability. The unique combination of coagulant protein-free condition with CHI-C showcases not only coagulopathy-independent blood clotting properties (efficacy) but also exceptional clinical potential, meeting all necessary biocompatibility evaluation (safety) without inclusion of conventional coagulation triggering proteins such as thrombin or fibrinogen. As a result, the CHI-C/Geln is approved by the Ministry of Food and Drug Safety (MFDS, Republic of Korea) as a class II medical device. Hemostatic efficacy observed in multiple animal models further demonstrates the superiority of CHI-C/Geln sponges in achieving quick hemostasis compared to standard treatments. This study not only enriches the growing body of research on mussel-inspired materials but also emphasizes the potential of biomimicry in developing advanced medical materials, contributing a promising avenue toward development of readily accessible and affordable hemostatic materials.

Low-Viscous, Dilute Phase Adhesive from Dense Polyphenolic Coacervates of Poly(vinyl alcohol) and Tannic acid.

This study explores a polyphenolic coacervate, named VATA, formed by poly(vinyl alcohol) (PVA) and tannic acid (TA). Distinct from conventional studies that have focused on the bottom, dense phase of coacervates, this research emphasizes the top, dilute phase, low-viscous coacervate liquid termed liquid-VATA (l-VATA). Due to TA's capability of intermolecular association as well as adhesiveness, phenomena not typically observed in the upper dilute phase of standard polyelectrolyte-based coacervates are revealed. At first glance, the dilute phase l-VATA coacervate resembles a water-like, low-viscous mixture solution of PVA, TA, and PVA/TA complexes. However, analysis shows that nearly all of the TA molecules associate with PVA chains, forming PVA/TA complexes. Furthermore, supraparticular association was observed between PVA/TA complex nanoparticles upon applying external shear force. A broad survey of shear rate and strain showed that the solution exhibited sequential shear-thickening, followed by shear-thinning behavior. The water-like, low viscosity of l-VATA unexpectedly reveals robust adhesiveness and thus able to lift an entire mouse using just a single human hair strand. Even in cases of failure, no interfacial failure was detected between mouse and human hair. In addition to enabling hair-to-hair bonding, our study also showcases the efficacy of l-VATA in facilitating hair-to-skin adhesion. The results illustrate how the lower viscosity of l-VATA can be exploited for a wide range of industrial and cosmetic applications, allowing the formulation of thin, uniform adhesive layers, something unachievable with the dense, viscous VATA glue. Thus, this study highlights the importance of investigating the top dilute phase of coacervates, shedding light on an area often underestimated compared to the bottom dense phase reported in prevalent coacervate studies.

Temperature- and pH-induced dual-crosslinked methylcellulose/chitosan-gallol conjugate composite hydrogels with improved mechanical, tissue adhesive, and hemostatic properties.

Gauze or bandages are commonly used to effectively control bleeding during trauma and surgery. However, conventional treatment methods can sometimes lead to secondary damages. In recent years, there has been increased interest in developing adhesive hemostatic hydrogels as a safer alternative for achieving hemostasis. Methylcellulose (MC) is a well-known thermo-sensitive polymer with excellent biocompatibility that is capable of forming a hydrogel through physical crosslinking owing to its inherent thermo-reversible properties. However, the poor mechanical properties of the MC hydrogel comprising a single crosslinked network (SN) limit its application as a hemostatic material. To address this issue, we incorporated a chitosan-gallol (CS-GA) conjugate, which has the ability to form chemical crosslinks through self-crosslinking reactions under specific pH conditions, into the MC hydrogel to reinforce the MC hydrogel network. The resulting MC/CS-GA hydrogel with a dual-crosslinked network (DN), involving both physical and chemical crosslinks, exhibited synergistic effects of the two types of crosslinks. Thus, compared with those of the SN hydrogel, the composite DN hydrogel exhibited significantly enhanced mechanical strength and tissue adhesive properties. Moreover, the DN hydrogel presented excellent biological activity in vitro. Additionally, in rat hepatic hemorrhage models, the DN hydrogel exhibited high hemostatic efficiency, showcasing its multifunctional capabilities.