This study introduces an advanced bioanalytical platform that combines digital microfluidics (DMF) with Raman spectroscopy, effectively addressing common issues in bioanalysis such as sample contamination, excessive consumption of samples and reagents, and manual handling. Our innovative system is engineered to handle diverse sample types and enables both sample preparation and in-situ analysis on a single device, utilizing less than 5 mu L of samples and reagents. It incorporates a Translucent Raman Enhancement Stack (TRES) sensor, which boosts the detection signal, and includes droplet-driving functionality for automated processing of complex samples in a compact setting. The hydrophilic surface of the TRES sensor draws analytes into the detection zone, expediting sample attachment and enhancing the surface-enhanced Raman scattering (SERS). Moreover, the TRES sensors are cost-effective, straightforward to manufacture, and scalable, making them suitable for widespread production and single-use bioanalytical applications. This integrated and automated approach streamlines the sample preparation and analysis processes, enhances detection efficiency, and achieves high sensitivity, excellent linearity, and effective detection of different biochemical analytes. We validate the system's accuracy through on-device enrichment and analysis of exosomes from serum, demonstrating its capability for real-time, on-site analysis of complex biological samples.
Wound care for open wounds is essential for reducing pain, protecting open wounds, speeding up the healing process and avoiding scar formation. Among the various three-dimensional (3D) carrier biomaterials such as films, sponges, and hydrogels, hydrogels are chemically and physically most similar to the natural extracellular matrix (ECM). Meanwhile, hydrogels are also common 3D carriers that can be efficiently loaded with drugs or cells. In addition, it forms a protective barrier on the wound surface to prevent secondary external infections and has the effect of directing skin cell expansion, tissue infiltration, and wound closure. However, the role of functional drugs in wound healing also faces a number of issues such as resistance, dosage, activity, and stability; therefore, a richer array of therapies is needed for wound repair and other areas of development. Physiotherapy, also known as nonpharmacological therapy, is a commonly used clinical treatment. Recently, more and more physiotherapy have been used for wound repair due to their high efficiency and low irritation. In recent reports, many researchers have tended to use hydrogel dressings in combination with physiotherapy, and this combination therapy is beneficial because it can both protect the wound microenvironment and accelerates wound healing. Therefore, this paper reviews the combined use of hydrogel dressings and physiotherapy in wound healing. We present the characteristics of hydrogel and physiotherapy and focus on the progress and problems of these two combined therapies in recent years.
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a significant public health challenge, necessitating the development of innovative antibacterial strategies. Nanomaterials are recognized for their ability to serve as photothermal conversion agents, transforming light energy into heat for antibacterial applications. These materials act as biological enzymes capable of generating reactive oxygen species (ROS), leveraging their catalytic activity to combat infections. While they show considerable promise, enhancing their ROS-generating efficiency and overall catalytic performance remains a critical challenge. In this work, a high catalytic bimetallic nanoplatform was developed, building on "large electronegativity difference induction/etchassisted/diffusion termination" mechanism to improve antibacterial efficacy. The synthesized nanoparticles were found to exhibit exceptional photothermal conversion efficiency and surface defects, enabling efficient bacterial eradication. Both in vitro and in vivo experiments demonstrated that H-Pt3Sn nanoparticles effectively eliminated MRSA while significantly inhibiting and disrupting biofilms formed by the pathogen. The nanoparticles also facilitated tissue repair by modulating macrophage-related molecular markers. In conclusion, this study presents a promising photothermal synergistic nanosystem with high catalytic functionality for advanced anti-infective applications.
Tendon injury is a common orthopedic condition that often results in local functional impairment and reduced quality of life. Due to the inherently low metabolic activity of tendon tissue and the inflammatory microenvironment at the injury site, its healing process is often suboptimal. Supramolecular hydrogen-bonded and dynamically covalent self-assembled chitosan-collagen-tannic acid (CCTA) microspheres were prepared using microfluidic technology. Molecular dynamics simulations, XRD analysis, thermogravimetric curves, Fourier transform infrared spectroscopy (FTIR), and XPS N1s spectra collectively revealed the formation of hydrogen bonds between the phenolic hydroxyl groups of tannic acid and the dynamic Schiff base structures formed via the oxidation of tannic acid with the amino groups of chitosan and CF1552, achieving self-assembled crosslinking. Chitosan, CF1552, and tannic acid act as bioactive components directly in the self-assembly process, replacing exogenous inactive components and carriers, thus achieving high biocompatibility while avoiding potential toxicity associated with non-bioactive polymers. Furthermore, the catechol groups in tannic acid exhibit antiinflammatory and antioxidant properties, suppressing oxidative stress and inflammation to balance the inflammatory microenvironment, thereby regulating extracellular matrix metabolism and preventing tendon degeneration. In a rat tendon injury model, CCTA significantly enhanced tendon mechanical strength, reduced oxidative stress and inflammation, and promoted tendon regeneration and functional recovery. Additionally, RNA sequencing identified potential healing mechanisms, including key genes and signaling pathways, providing a foundation for further clinical treatment strategies. In summary, the developed multifunctional platform offers a promising option for tendon injury treatment.
Photoactivatable peroxynitrite (ONOO-), with prolonged half-life, enhanced diffusion, and precise spatiotemporal control, has emerged as a potent anti-biofilm and antimicrobial agent. However, conventional ONOO- generators are usually designed using planar molecular skeletons, which suffer from aggregate-caused reactive oxygen species reduction, thereby restricting ONOO- production. Herein, we present the series of photoactivatable ONOO- generators with aggregation-induced emission (AIE) characteristics-PyTP-NO, PyPTP-NO, and +PyPTP-NO-among which +PyPTP-NO enables efficient ONOO- production. Enhancing electron-withdrawing capability and extending pi-conjugation has proven to be an effective strategy for designing ONOO--generating AIEgens, as the resulting increases in excitation coefficients and intersystem crossing promote both superoxide anion generation and nitric oxide (NO) release, thereby boosting ONOO- production. To overcome the biofilm barrier, +PyPTP-NO was further incorporated into the fast-dissolving tips of a bilayer microneedle patch (+PyPTP-NO@DMN) to enable rapid release of the +PyPTP-NO for efficient biofilm eradication, while the base layer was loaded with recombinant collagen (CF-1552) to facilitate wound healing. Post-activation, +PyPTP-NO converts to the non-toxic product +PyPTP-NH, minimizing photo-toxicity to ensure biosafety during wound healing. This study not only provides a generalizable molecular design strategy for developing efficient ONOO- generators but also establishes a versatile therapeutic platform that enables effective biofilm eradication and safe tissue regeneration.
Traumatic non-compressible hemorrhage and subsequent wound management remain critical challenges in military and civilian settings to this day. Cryogels have emerged as promising hemostatic materials for non-compressible hemorrhage due to their blood-triggered shape recovery. In this study, a biodegradable and mechanically resilient cryogel (CF/PD) was produced via cryopolymerization, employing methacrylated recombinant collagen as a macromolecular crosslinker alongside poly (ethylene glycol) diacrylate (PEGDA) and dopamine methacrylate (DMA). With its interpenetrating macro-porous structure and high hydrophilicity, the CF/PD rapidly absorbs blood and returns to its original shape within 1.5 s. In a rat liver defect model, CF/PD outperformed commercially available gelatin sponges, reducing hemostasis time by 74.4% and blood loss by 76.5%. Moreover, CF/PD cryogels facilitate in situ tissue regeneration by virtue of the bioactivity and degradability of recombinant collagen. This work establishes a bioactive recombinant collagen-driven cryogel platform, offering a transformative solution for managing non-compressible hemorrhage while enabling tissue regeneration.
Androgenetic alopecia (AGA) is recognized as a prevalent androgen-mediated disorder characterized by progressive follicular miniaturization and irreversible hair loss, primarily driven by the pathological elevation of dihydrotestosterone (DHT) that disrupts hair follicle microenvironment and induces follicular cells damage. This condition frequently results in profound psychosocial distress and diminished quality of life among affected individuals. In this study, we introduced a novel microneedle-based drug delivery system (CK/GSNO@Lip MN) for the synergistic treatment of AGA. The system was ingeniously engineered for the co-delivery of Ginsenoside Compound K (CK) and S-nitrosoglutathione (GSNO), which possessed distinct hydrophobicities and release kinetics. Specifically, the hydrophobic drug CK activated the PI3K-AKT signaling pathway to upregulate β-catenin expression, while concurrently modulating reactive oxygen species (ROS) levels and alleviating excessive inflammatory responses. Meanwhile, the hydrophilic nitric oxide (NO) donor GSNO released NO to enhance angiogenesis and synergistically regulated inflammatory homeostasis in conjunction with CK, thereby creating a favorable microenvironment for hair regeneration. Ultimately, CK/GSNO@Lip MN achieved significant hair regeneration by modulating the hair follicle microenvironment and promoting the proliferation of follicular cells. This innovative therapeutic strategy provided a comprehensive approach to AGA treatment, with promising potential for broader dermatological applications.
Electron acceptor possessing strong electron-withdrawing ability and exceptional stability is crucial for developing donor-acceptor-donor (D-A-D) structured aggregation-induced emission luminogens (AIEgens) with second near-infrared (NIR-II) emission. Although 6,7-diphenyl-[1,2,5] thiadiazolo [3,4-g] quinoxaline (PTQ) and benzobisthiadiazole (BBT) are widely employed as NIR-II building blocks, they still suffer from limited electron-withdrawing capacity or inadequate chemo-stability under alkaline conditions. Herein, a boron difluoride formazanate (BFF) acceptor is utilized to construct NIR-II AIEgen, which exhibits a better overall performance in terms of NIR-II emission and chemo-stability compared to the PTQ- and BBT-derived fluorophores. With finely tuned intramolecular motions and strong D-A interaction strength, TPE-BFF simultaneously exhibits high molar extinction coefficient (ε= 4.31 × 104 M-1cm-1), strong NIR-II emission (Φ = 0.49%) and photothermal effect (η = 58.5%), as well as high stability. Thanks to these merits, the thermosensitive nanoparticles constructed by integrating TPE-BFF and the antiglycolytic agent 2-deoxy-d-glucose (2DG) are successfully utilized for imaging-guided photothermal antitumor lung metastasis by regulating glycolysis and reducing ATP-dependent heat shock proteins. Combining experimental results and theoretical calculations, BFF proves to be an outstanding electron acceptor for the design of versatile NIR-II AIEgens. Overall, this study offers a promising alternative for developing multifunctional NIR-II AIEgens in biomedical applications.
Generally, diabetic wounds heal very slowly and inefficiently with an increasing risk of infections. Recent nanotechnology and biomaterial advances elaborate developed multi-functional hydrogels and nanoparticles offer promising solutions to accelerate wound healing for diabetic patients. This research work demonstrates to use of solvent diffusion method to develop hydrogel nanocomposites composed of chitosan (CS), hyaluronic acid (HA), gold (Au), and fibroblast growth factors (FGF). The biological analysis of nanocomposites exhibited enhanced wound healing efficiency by incorporating bioactive molecules like FGF and bioactive Au nanoparticles. In vitro, cell compatibility analysis (MTT assay) of prepared hydrogel nanocomposites was studied on fibroblast cell lines NIH-3T3-L1 and L929 and exhibited greater cell survival ability (>90 %), cell proliferation and migration ability, which demonstrated the suitability of nanocomposite for wound healing treatment. In vitro, anti-bacterial analyses established that FGFAu@CS/HA has strong antibacterial effectiveness against gram-positive and gram-negative pathogens. The observation of the present research revealed that prepared FGF-Au@CS/HA hydrogel composites could be a suitable biomaterial for diabetic wound care, potentially improving its antibacterial and healing efficacies.
The skin is the body's primary immune barrier, defending it against pathogenic invasion. Skin injuries impose a significant physiological burden on patients, making effective wound management essential. Dressings are commonly employed in wound care, and electrospun nanofiber dressings are a research hotspot owing to their ease of fabrication, cost-effectiveness, and structural similarity to the extracellular matrix. Coaxial electrospinning offers considerable advantages in drug delivery, fiber structure transformation, and enhanced interaction with the host. These attributes make coaxial electrospun materials promising candidates for precision and personalized wound dressings in medical treatments. This review provides a comprehensive overview of wound healing and its influencing factors. It also outlines coaxial electrospinning's production principles and benefits in wound dressings. Guided by the factors affecting wound healing, coaxial electrospun nanofiber dressings have different application modalities. Furthermore, we discuss the current limitations and future directions for enhancing the current coaxial electrospun dressing technologies.
The G-quadruplex (GQ) formed by guanine-rich DNA strands exhibits superior thermal stability and electric properties, which have generated substantial interest in applying GQ DNA to bioelectric interfaces.
The existence of biofilm remains a significant impediment to the healing of chronic wounds, including diabetic wounds. The dense extracellular polymeric substance (EPS) barrier of biofilms leads to poor drug permeability, making biofilms eradication a challenging task. Additionally, high glucose levels hinder the process of wound healing. To address these issues, we developed a multi-enzyme cascade microneedle system (MN) by combining enzymatic biofilm disruption with GOx-based chemodynamic therapy (CDT) for the first time. The microneedle tip dissolves quickly and delivers α-amylase and glucose oxidase-loaded metal–organic framework MIL-101 (M@G) into the biofilm’s interior. The α-amylase disintegrates the EPS structure, making the bacteria vulnerable and producing glucose as a substrate for the next cascade reaction. Next, GOx uses the glucose produced from EPS degradation and present at the wound site to produce significant amounts of H2O2, which is then transformed to reactive oxygen species (ROS) through MIL-101. The system eradicates methicillin-resistant Staphylococcus aureus (MRSA) biofilms by sequentially destroying EPS, consuming glucose at the wound, and self-supplying H2O2 to produce ROS, thereby reducing glucose concentrations and concurrently decreasing bacterial infection and inflammatory responses. Additionally, the pro-angiogenic peptide functionalized hydrogel (Gel-Q-M) serves as a backing to promote collagen deposition and angiogenesis, thereby accelerating the healing of chronic wound. In conclusion, the constructed MN platform showed excellent anti-biofilm and angiogenic properties in vitro, which could effectively eliminate biofilm, reduce inflammation and promote diabetic wound repair.
In recent years, microneedle technology has been widely used for the transdermal delivery of substances, showing improvements in drug delivery effects with the advantages of minimally invasive, painless, and convenient operation. With the development of nano- and electrochemical technology, different types of microneedles are increasingly being used in other biomedical fields. Recent research progress shows that dissolving microneedles have achieved remarkable results in the fields of dermatological treatment, disease diagnosis and monitoring, and vaccine delivery, and they have a wide range of application prospects in various biomedical fields, showing their great potential as a form of clinical treatment. This review mainly focuses on dissolving microneedles, summarizing the latest research progress in various biomedical fields, providing inspiration for the subsequent intelligent and commercial development of dissolving microneedles, and providing better solutions for clinical treatment.
Noncompressible wounds resulting from accidents and gunshots are typically associated with excessive bleeding, slow wound healing, and bacterial infection. Shape-memory cryogel presents great potential in controlling the hemorrhaging of noncompressible wounds. In this research, a shape-memory cryogel was prepared using a Schiff base reaction between alkylated chitosan (AC) and oxidized dextran (ODex) and then incorporated with a drug-laden and silver-doped mesoporous bioactive glass (MBG). Hydrophobic alkyl chains enhanced the hemostatic and antimicrobial efficiency of the chitosan, forming blood clots in the anticoagulated condition, and expanding the application scenarios of chitosan-based hemostats. The silver-doped MBG activated the endogenous coagulation pathway by releasing Ca2+ and prevented infection through the release of Ag+. In addition, the proangiogenic desferrioxamine (DFO) in the mesopores of the MBG was released gradually to promote wound healing. We demonstrated that AC/ODex/Ag-MBG DFO(AOM) cryogels exhibited excellent blood absorption capability, facilitating rapid shape recovery. It provided a higher hemostatic capacity in normal and heparin-treated rat-liver perforation-wound models than gelatin sponges and gauze. The AOM gels simultaneously promoted infiltration, angiogenesis, and tissue integration of liver parenchymal cells. Furthermore, the composite cryogel exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli. Thus, AOM gels show great promise for clinical translation in treating lethal, noncompressible bleeding and the promotion of wound healing.
皮肤是身体与外界环境的保护屏障,也是人体最大的器官.在深度损伤和烧伤的情况下,皮肤愈合过程并不充分,从而导致慢性伤口最终可能导致截肢和死亡.从人口统计学角度看,慢性伤口和愈合障碍患者的数量逐渐达到流行病的比例,并将在人类健康和经济方面造成更大的负担[1-2].
Objective :In order to enrich and innovate new healthy food with antioxidant function,explore grape seeds-chrysanthemum-inulin compound antioxidant capacity of aged mice and provide theoretical basis for its application in healthy food. Methods :Mice over 8 months were randomly divided into aging control group,mixtures of low,medium and high dose groups(0.58,1.17 and 2.33 g/kg respectively),and 4-week-old mice were selected as young group. After 30 days of gavage,superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA)and protein carbonyls(PC)levels in serum as well as liver tissue and brain tissue of mice were examined;the pathological changes of liver tissue were observed under microscope. Results :Compared with the control group,grape seed-chrysanthemum-inulin compound could significantly increase SOD activity and GSH content and decrease MDA and PC content(P < 0.01,P < 0.05 respectively)in serum,liver tissue and brain tissue of aged mice. According to pathological section of liver tissue,compared with aged group,with the increase of compound dosage,the morphology of liver cells in the treated groups was gradually complete,and the number of cells increased and arranged neatly. Conclusion :Grape seed–chrysanthemum-inulin mixture could improve antioxidant capacity in aged mice.
The biofilms present in wounds are difficult to eliminate due to the compact barrier formed by extracellular polymeric substances (EPS). Herein, we have designed a dissolvable microneedle patch that destroys the structure of EPS matrix by enzymolysis and kills the exposed bacteria by the combination of photothermal-and chemo-therapy. The microneedles can destroy the physical barrier of biofilms and release alpha-amylase to degrade the extracellular polysaccharide of EPS, making the bacteria susceptible to antimicrobial therapies. Furthermore, the levofloxacin-loaded polydopamine nanoparticles (PDA@Levo) encapsulated in microneedles can achieve both antibiotic and mild photothermal therapy (PTT, 50 degrees C) under 808 nm laser irradiation to synergistically eradicate bacteria. The combined use of enzymolysis, antibiotics and PTT therapy effectively removed the biofilms. The in vitro experiments showed the biomass of biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa was reduced to 12.6% and 31.3%, respectively. In vivo, the alpha-amylase-PDA@Levo microneedle (MN) could remove biofilms from infected wounds and kill exposed bacteria, thereby reducing inflammation and further facilitating the wound healing process, while the mild PTT did not cause damage to normal tissues. We believe that this new multimodal therapy microneedle patch holds great potential in combating bacterial biofilms that are associated with wound infections.
The excessive inflammation, oxidative stress, and impaired angiogenesis are major factors leading to difficulties in chronic wound healing. To develop bioactive materials with intrinsic antioxidant and anti-inflammatory properties, we prepared hydrogels for the first time using paramylon secreted by Euglena gracilis which is a polysaccharide has been approved by FDA as food additive. Results showed that the paramylon hydrogel has favourable anti-inflammatory effects and the ability to scavenge reactive oxygen species (ROS) through free radical destruction, deoxygenation, and singlet oxygen quenching, and inhibit ROS production by chelating the metal ions required for the formation of ROS. We found that the paramylon hydrogel could effectively reduce wound inflammation and promote angiogenesis to facilitate wound repair. Furthermore, for the first time, we found that paramylon hydrogel could promote the formation of blood vessels via the HIF-1α-VEGF pathway. These results indicated that the highly bioactive paramylon could be the preferred material for wound healing.