Wenjun Miao

Skin wounds require complex interventions to overcome hemorrhage, infection, and delayed repair, which are multifunctional needs that current dressings rarely meet. Herein, we developed a platelet-loaded hyaluronic acid/gelatin (HA/GEL/P) anisotropic cryogel with integrated hemostatic, antibacterial, and regenerative properties. The anisotropic cryogel prepared through directional freezing exhibited aligned fibrous microstructures that facilitated the directed cell migration and proliferation. Concurrently, bioactive molecules released by activated platelets promote rapid hemostasis and synergistically enhance cell proliferation, angiogenesis and antibacterial effects. In a mouse wound model infected with Staphylococcus aureus, HA/GEL/P significantly accelerated wound closure by optimizing vascular and immune microenvironments to promote organized extracellular matrix (ECM) remodeling. Histological analysis confirmed reduced infection and inflammation, coupled with improved collagen deposition and re-epithelialization. These results highlight the HA/GEL/P anisotropic cryogel as a promising multifunctional dressing for complex wound healing and advanced biomedical applications.

Coamorphous formulations have emerged as a promising strategy to improve the solubility and bioavailability of poorly soluble drugs, but their application is often limited by inherent thermodynamic instability. Herein, we propose an unconventional plasticizer strategy to stabilize coamorphous systems. The ternary coamorphous systems of baicalein (Bai), piperine (Pip), and resveratrol (Res) at 1:1:1, 1:2:1, 1:3:1, and 1:4:1 molar ratios were successfully prepared and exhibited enhanced supersaturated dissolution profiles, with approximately 3.4-, 5.3-, and 4.6-fold increases in the apparent solubilities of Bai, Pip, and Res, respectively. Pip as a plasticizer increased molecular mobility and lowered Tg from 107.5 to 52.3, 45.7, and 37.5 °C with increasing Pip content. Unexpectedly, coamorphous systems with higher Pip ratios exhibited enhanced physical stability. Fourier-transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance spectroscopy, molecular dynamics simulations, and quantum chemical calculations revealed a composition-dependent redistribution of intermolecular interactions. With increasing Pip content, Pip preferentially associated with Res and subsequently interacted with Bai, progressively disrupting the pre-existing Res−Bai hydrogen bond (HB). Meanwhile, the normalized HB numbers decreased, while the normalized binding energies remained nearly unchanged. Furthermore, the systems with a higher Pip ratio prolonged the intermittent HB lifetime with fast HB breaking and reformation (i.e., dynamic hydrogen bonding). Pip-mediated interaction reorganization and dynamic HB jointly contributed to the improved stability. This work provides a promising strategy for stabilizing coamorphous systems via plasticizers capable of establishing reorganized heteromolecular interactions and dynamic hydrogen bonding.

MicroRNAs (miRNAs) are post-transcriptional gene regulators and promising tumor biomarkers. Traditional detection methods are limited by high cost and specialized equipment. DNA-templated silver nanoclusters (DNA-AgNCs) are attractive fluorescent materials for biosensing but suffer from suboptimal brightness, with existing fluorescence enhancement strategies lacking universality. This study introduces a novel hydrogel kit integrating photonic crystals (PCs) and DNA-AgNCs for portable detection of miRNA-21. The formation of AgNCs within hybridization chain reaction (HCR) monomers generates a fluorescence signal, which is further amplified by PCs. Upon addition of miRNA-21, the conformational changes induced by miRNA-21 in the monomers trigger a cascade of hybridization events. Meanwhile, the formation of silver nanoclusters (AgNCs) is inhibited, thereby leading to an obvious decrease in fluorescence signal that can be distinguished by the naked eye. Hence, through the synergy of HCR-mediated target recognition, fluorogenic AgNCs-based transduction units, and PCs-triggered signal amplification, the hydrogel kit enhances the convenience and specificity of miRNA detection. In conclusion, this kit enables high-throughput fluorescence detection with a range of 1.56 to 200 nM. Moreover, it exhibits robust anti-interference capability in serum analysis, with recovery rates ranging from 91.84 to 102.74%. Owing to its strong matrix tolerance, the kit facilitates facile miRNA-21 detection, overcomes the drawbacks of conventional approaches, and holds considerable promise for clinical tumor diagnostic applications.

Purpose: Compared to conventional photodynamic therapy (PDT), oxygen-affording PDT represents a promising strategy for treating multidrug-resistant (MDR) gram-negative bacterial infections due to its enhanced sensitization ability towards bacteria and amplified therapeutic efficacy. Over the last decade, various nanoplatforms for the co-delivery of oxygen and photosensitizers have been developed. However, their application in the treatment of infectious diseases is hampered by their poor stability and easy clearance by the reticuloendothelial system (RES). Methods: To address these obstacles, we reported an erythrocyte membrane (EM) camouflaged nanoemulsion containing chlorin e6 (Ce6) and perfluorocarbon (FDC), named ECF, showing good colloidal stability and long-circulating potential, making it suitable for fighting against MDR Gram-negative bacterial infections. The nanoemulsion was fabricated and characterized. The oxygen loading and release performance, photodynamic activity, and bactericidal performance of ECF against Acinetobacter baumannii (A. baumannii) were evaluated. Furthermore, the antiphagocytosis profile was tested in vitro using Raw 264.7 cells. In addition, the pharmacokinetic behavior and therapeutic efficiency of ECF were studied in vivo. Results: ECF exhibited superior oxygen loading and release behavior, potent photodynamic activity, and negligible toxicity to mammalian cells. Upon light irradiation, the antibacterial rate of preoxygenated-ECF reached 98% at 40 μg mL^{− 1} of Ce6 and the bactericidal activity of preoxygenated-ECF and Gen was 3.3 folds higher than that of Gen. Furthermore, ECF could effectively inhibit uptake by phagocytes and circulate in the blood 1.5-fold longer than that of nanoemulsion without EM modification (CF) following intravenous administration. In addition, preoxygenated-ECF combined with antibiotic plus light irradiation showed prominent therapeutic efficacy in treating A. baumannii-induced acute peritonitis, accompanied by good biocompatibility in vivo. Conclusion: Our results provide a novel paradigm for evading immune clearance, prolonging retention time and improving synergetic bactericidal capacity in combination with PDT and antibiotic therapy against planktonic bacteria and gram-negative bacterial infections.

MicroRNAs (miRNAs) in dermal interstitial fluid (ISF) have recently been recognized as clinically promising biomarkers for the diagnosis and prognosis of cancer. However, the detection poses significant challenges, primarily due to the low abundance of miRNAs and the limitations of current sampling techniques. To address this issue, we develop novel porous microneedles (PMNs) array-based sensor composed of poly(vinyl alcohol) porous hydrogel and DNA-templated silver nanoclusters (AgNCs) to facilitate the enrichment and highly sensitive detection of ISF miRNA. Leveraging the capillary action facilitated by its unique porous structure and the swelling properties of the hydrogel, the PMNs array can efficiently extract 2.7 ± 0.3 mg of ISF within 5 min. Additionally, the interconnected pores within the PMNs array contribute to an increased specific surface area, thereby offering a convenient platform for the decoration of DNA-templated AgNCs. The immobilized large amount of AgNCs effectively capture the target miRNA from the extracted ISF, resulting in miRNA-induced fluorescence quenching of AgNCs. Subsequently, the introduction of the duplex-specific nuclease leads to the cleavage of DNA in DNA-RNA heteroduplexes, which release miRNA to interact with other AgNCs. This process of target recycling triggers a further reduction in fluorescence intensity, thereby enabling sensitive detection of the low-abundant miRNA down to 1.6 pM. Both in vitro and in vivo experiments validate the efficacy of the AgNCs immobilized PMNs array for the detection of miRNA biomarkers in ISF within minutes. These results indicate that the proposed PMNs array-based sensor holds great potential for the development of noninvasive personalized diagnostic strategies.

Platelet-derived extracellular vesicles (PEVs) showing great potential in wound healing have attracted increasing attention recently. Nondestructive isolation and effective utilization strategies are highly conducive for PEVs developing into recognized therapeutic entities. Here, we present an efficient strategy for PEV isolation and bacterial infected wound healing based on self-assembled DNA microflowers. First, DNA microflowers are prepared using rolling circle amplification. Then, the hydrophobic interaction between cholesteryl modified on DNA microflowers and the phospholipid bilayer membrane of PEVs leads to the formation of a network structure with improved mechanical strength and the separation of PEVs from biological samples. Finally, controlled release of PEVs is achieved through bacterial-induced hydrogel degradation. In vitro experiments demonstrate the obtained DNA hydrogel with good cytocompatibility and therapeutic potential. Taken together, the DNA microflower-based hydrogels with bioadhesive, self-healing, tunable mechanical properties and bacteria-responsive behavior offer substantial potential for EV isolation and wound healing.