Acid Hydrogel Research Articles

Framework Nucleic Acid-Based Selective Cell Catcher for Endogenous Stem Cell Recruitment.

Cell-surface engineering holds great promise in boosting endogenous stem cell attraction for tissue regeneration. However, challenges such as cellular internalization of ligand and the dynamic nature of cell membranes often complicate ligand-receptor interactions. The aim of this study is to harness the innovative potential of programmable tetrahedral framework nucleic acid (tFNA) to enable precise, tunable ligand-receptor interactions, thereby improving stem cell recruitment efficiency. This approach involves experimental screening and theoretical analysis using dissipative particle dynamics. The results demonstrate that altering the flexibility and topology of ligands on tFNA changes their cellular internalization and membrane binding efficiency. Furthermore, optimizing the distribution of the mesenchymal stem cell (MSC)-binding aptamer 19S (Apt19S) on the tFNA enhances the stem cell capture efficiency. Following successful in vitro MSC capture, Apt19S-modified tFNA is chemically linked to a hyaluronic acid hydrogel, forming an efficient "stem cell catcher" system. Subsequent in vivo experiments demonstrate that this system effectively promotes early stem cell recruitment and accelerates bone regeneration in different bone healing scenarios, including cranial and maxillary defects.

Kinetic and Mechanistic Release Studies on Hyaluronan Hydrogels for Their Potential Use as a pH-Responsive Drug Delivery Device

Hyaluronic acid, a biocompatible polymer, holds significant potential for drug delivery applications. Its variable degree of protonation, which entails tunable physical properties, makes it an ideal candidate for developing pH-sensitive hydrogels. Like other smart drug delivery systems, pH-responsive hydrogels can enhance medical treatment and expedite the healing process. However, the inherent complexity of hydrogels poses challenges in identifying suitable matrix systems. This study evaluates the potential of thiolated hyaluronic acid hydrogels, physically cross-linked with deacetylated disaccharide units of the polymer, for use in drug delivery. Using low-molecular-weight dextrans as model drugs, we investigated the system’s response to different pH environments in terms of swelling as well as the kinetic and mechanistic release of the encapsulated compound. The data suggest tunable release properties of the gel regarding drug size and pH value. Our results demonstrate the gel system’s potential for smart drug delivery. We anticipate that this system is a promising candidate for use in transdermal wound healing applications and strongly encourage further investigations using other sorts of (model) drugs to gain a more detailed insight into its pH-responsive transport qualities.

Retraction Note: Biocompatibility and Antimicrobial Investigation of Agar-Tannic Acid Hydrogel Reinforced with Silk Fibroin and Zinc Manganese Oxide Magnetic Microparticles

Retraction Note: Biocompatibility and Antimicrobial Investigation of Agar-Tannic Acid Hydrogel Reinforced with Silk Fibroin and Zinc Manganese Oxide Magnetic Microparticles

DDDR-29. MATRIX STIFFNESS INDUCED PHENOTYPE IN BRAIN METASTATIC BREAST CANCER CELLS DETERMINES RESPONSE TO THERAPY

Abstract Breast cancer is the most prevalent form of cancer, representing 12.5% of all cancer cases diagnosed worldwide. Breast cancer cells can metastasize to distant organs (i.e., brain) and remain dormant for extended periods of time. This aspect makes it very difficult to treat these cells as they exhibit reduced growth as well as resistance to therapy. Despite advances in our understanding of breast cancer metastasis, the specific mechanisms that enable dormant cancer cells to resist therapeutics, particularly in brain metastatic breast cancer (BMBC), remain unclear. Herein, we employed brain tissue mimetic hyaluronic acid (HA) hydrogels of varying stiffness (i.e., ~0.4 kPa vs. ~4.5 kPa) to investigate the response to chemo or targeted therapy in dormant versus proliferative BMBC cells. It was revealed that BMBC cells grown on soft HA hydrogels (~0.4 kPa) displayed a non-proliferative (i.e., dormant) phenotype and exhibited resistance to Paclitaxel (PTX) or Lapatinib (LAP). However, BMBC cells grown on stiff HA hydrogels (~4.5 kPa) displayed a proliferative phenotype and sensitivity to PTX or LAP. Furthermore, we found that resistance to therapy was due to the enhanced expression of the serum/glucocorticoid regulated kinase 1 (SGK1) gene, mediated, in part, via the p38 mitogen-activated protein kinase (MAPK) pathway. Consequently, SGK1 inhibition using a SGK inhibitor in BMBC cells cultured on soft HA hydrogels resulted in a dormant-to-proliferative switch as well as response to PTX or LAP. In sum, our study demonstrated that matrix stiffness plays a major role in the dormancy-associated therapy response, mediated, in part, via the p38/SGK1 pathway.

ANGI-14. DRUGGABLE GENOME CRISPR SCREEN IN 3D HYDROGEL DEVICES REVEALS TARGETABLE KINASES AND PHOSPHATASES IMPLICATED IN CYTOSKELETAL REORGANIZATION IN INVADING GBM CELLS

Abstract The invasive nature of glioblastoma cells into adjacent brain tissues is a key factor in its unfavorable prognosis. To decipher the mechanisms driving glioblastoma invasion, we developed microdissectable biomimetic 3D hydrogel invasion devices containing hyaluronic acid hydrogels decorated with integrin-binding peptides (RGD) and crosslinked with protease-cleavable crosslinkers. The ability to disassemble these devices and interrogate cells in the core vs. invasive fraction allows for high throughput screens. We thus performed a screen in GBM43 cells expressing CRISPR/Cas9 and a 13,250 gRNA library targeting the 2550 genes in the druggable human genome. Of seven initial hits from this screen, only two could be validated by single gene CRISPR and use of a drug to target the hit - ACP1 (also known as LMW-PTP) and Aurora Kinase B (AURKB). Integration of ChIP-seq and RNA-seq revealed no plausible transcriptional targets of ACP1 and AURKB that could drive invasion. Proximity labeling with the TurboID system identified CTTN (cortactin), an actin binding protein whose phosphorylation is integral to the formation of lamellipodia and invadopodia, as phosphorylated by AURKB and Ephrin A2 (EPHA2), whose dephosphorylation controls cell morphology, adhesion, migration and invasion by modifying the organization of the actin cytoskeleton and influencing the activities of integrins and intercellular adhesion molecules, as dephosphorylated by ACP1. These findings underscore the delicate balance between kinase and phosphatase activities in regulating the actin cytoskeleton broadly and at the cell’s front or “leading edge,” offering new therapeutic targets to disrupt the invasion that is a hallmark of glioblastoma.

Therapeutic potential of hyaluronic acid hydrogel combined with bone marrow stem cells-conditioned medium on arthritic rats’ TMJs

Conditioned media (CM) is derived from mesenchymal stem cells (MSC) culture and contains biologically active components. CM is easy to handle and reduces inflammation while repairing injured joints. Combination therapy of the CM with cross-linked hyaluronic acid (HA) could ameliorate the beneficial effect of HA in treating degenerative changes of articulating surfaces associated with arthritic rats’ temporomandibular joints (TMJs). This study aimed to evaluate the therapeutic potential of HA hydrogel combined with bone marrow stem cells-conditioned medium (BMSCs-CM) on the articulating surfaces of TMJs associated with complete Freund’s adjuvant (CFA)-induced arthritis. Fifty female Sprague-Dawley rats were divided randomly into five equal groups. Rats of group I served as the negative controls and received intra-articular (IA) injections of 50 µl saline solution, whereas rats of group II were subjected to twice IA injections of 50 µg CFA in 50 µl; on day 1 of the experiment to induce persistent inflammation and on day 14 to induce arthritis. Rats of group III and IV were handled as group II and instead, they received an IA injection of 50 µl HA hydrogel and 50 µl of BMSCs-CM, respectively. Rats of group V were given combined IA injections of 50 µl HA hydrogel and BMSCs-CM. All rats were euthanized after the 4th week of inducing arthritis. The joints were processed for sectioning and histological staining using hematoxylin and eosin, Masson’s trichrome and toluidine blue special staining, and immunohistochemical staining for nuclear factor-kappa B (NF-κB). SPSS software was used to analyze the data and one-way analysis of variance followed by post-hoc Tukey statistical tests were used to test the statistical significance at 0.05 for alpha and 0.2 for beta. In the pooled BMSC-CM, 197.14 pg/ml of platelet-derived growth factor and 112.22 pg/ml of interleukin-10 were detected. Compared to TMJs of groups III and IV, TMJs of group V showed significant improvements (P = 0.001) in all parameters tested as the disc thickness was decreased (331.79 ± 0.73), the fibrocartilaginous layer was broadened (0.96 ± 0.04), and the amount of the trabecular bone was distinctive (19.35 ± 1.07). The mean values for the collagen amount were increased (12.29 ± 1.38) whereas the mean values for the NF-κB expression were decreased (0.62 ± 0.15). Combination therapy of HA hydrogel and BMSCs-CM is better than using HA hydrogel or BMSCs-CM, separately to repair degenerative changes in rats’ TMJs associated with CFA-induced arthritis.

Licochalcone A loaded multifunctional chitosan hyaluronic acid hydrogel with antibacterial and inflammatory regulating effects to promote wound healing

The wound healing process is characterized by persistent infection and long-term inflammation. The licochalcone A (LicA) has the potential for skin wound healing and needs a good drug-loading platform to apply its antibacterial and anti-inflammatory effects. In this study, the LicA@chitosan (CS) -hyaluronic acid (HA) hydrogel with antibacterial and anti-inflammatory was developed for wound healing in mice. The SEM displayed that the hydrogel had an obvious porous structure and was very suitable to be used as a delivery carrier for LicA. The FTIR results suggested that the LicA can be effectively loaded in the CS-HA hydrogel. Variable strain scanning, frequency scanning and temperature scanning indicated that the LicA@CS-HA hydrogel can maintain the gel state. The LicA@CS-HA hydrogel had good biological safety, can inhibit the activity of Escherichia coli and Staphylococcus aureus, and can release LicA stably. The LicA@CS-HA hydrogel also has good adhesion and hemostatic properties. Finally, the LicA@CS-HA hydrogel significantly accelerated wound healing in mice skin injury model, and reduced inflammation and orderly collagen deposition were observed by HE and Masson staining. The immunohistochemistry indicated that the LicA@CS-HA hydrogel induced the positive expression of CD31, VEGF, and HIF-1α promoted neovascularization. The LicA@CS-HA hydrogel also down-regulated the expression of M1 macrophage markers CD86, IL-6, and TNF-α, and increased the expression of M2 macrophage markers CD206, IL-4, and IL-10 proteins. The molecular docking demonstrated that the target proteins had better binding activity to LicA. Collectively, the LicA@CS-HA hydrogel has broad application prospects in promoting wound healing.

Bioadhesive supramolecular polymer/hyaluronic acid hydrogel with zinc ion and dexamethasone slow release for diabetic wound healing

Bioadhesive supramolecular polymer/hyaluronic acid hydrogel with zinc ion and dexamethasone slow release for diabetic wound healing

Bio-inspired chitosan/polyvinyl alcohol/tannic acid hydrogels as plant grafting wood adhesives

Recently, there has been growing interest in plant-inspired materials for various biological, medical, and industrial applications. Notably, tannic acid-based materials exhibit remarkable adhesive properties and can be used in a variety of applications, particularly biomedical applications. In addition, mixtures composed of tannic acid and polymers (e.g., polyvinyl alcohol) exhibit excellent adhesion to various substrates. In this study, we developed gallol-containing chitosan (G-CS), polyvinyl alcohol (PVA), and tannic acid (TA) composite (G-CPT) hydrogels as wood adhesive materials. G-CPT hydrogels were immediately formed by mixing the G-CS/PVA solution with the TA solution. Rheological analysis revealed an increase in the elastic modulus (G′) with the addition of small amounts of G-CS. In addition, the detachment stress of wood sticks attached using G-CPT hydrogels was 142.2 ± 7.2 MPa, which was substantially higher than that of G-CS (5.3 ± 1.4 kPa), PVA (2.2 ± 0.2 kPa), TA (0.4 ± 0.1 kPa), and PVA/TA hydrogels (106.5 ± 2.5 MPa). Furthermore, G-CPT hydrogels can be used as wood adhesives for scion grafting into the rootstock of English ivy. These findings highlight the importance of G-CPT hydrogels as eco-friendly wood adhesives with enormous potential for various industrial and agricultural applications.

Photo-crosslinked hyaluronic acid hydrogels designed for simultaneous delivery of mesenchymal stem cells and tannic acid: Advancing towards scarless wound healing

The quest for scarless wound healing is imperative in healthcare, aiming to diminish the challenges of conventional wound treatment. Hyaluronic acid (HA), a key component of the skin's extracellular matrix, plays a pivotal role in wound healing and skin rejuvenation. Leveraging the advantages of HA hydrogels, this research focuses first on tuning the physicochemical and mechanical properties of photo-crosslinkable methacrylated HA (MAHA) by varying the methacrylation degree, polymer concentration, photo-crosslinker concentration, and UV exposure time. The optimized hydrogel, featuring suitable porosity, swelling ratio, degradability, and mechanical properties, was then used for the combined delivery of tannic acid (TA), known for its hemostatic, antibacterial, and antioxidant properties, and Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) cultured on the MAHA-TA hydrogel to enhance skin regeneration. The composite MAHA-TA-MSC hydrogel demonstrated favorable pores and biocompatibility, evidenced by cell viability, and promoted cell proliferation. When applied to dorsal wounds in rats, this composite hydrogel accelerated wound healing and reduced scarring. Additionally, molecular and histopathological analyses revealed increased expression of IL-10, the TGF-β3/TGF-β1 ratio, and the Collagen III/Collagen I ratio. These findings suggest that the MAHA-TA-MSC hydrogel is a promising candidate for scarless acute wound healing.

The oxidized hyaluronic acid hydrogels containing paeoniflorin microspheres regulates the polarization of M1/M2 macrophages to promote wound healing

Controlling excessive inflammation of acute wound is an effective means to shorten the healing time. Therefore, targeted control of the inflammatory response of the wound is a promising therapeutic strategy. In this study, paeoniflorin (Pae) was encapsulated in microspheres and combined with oxidized hyaluronic acid hydrogels to prepare the hydrogel loaded with Pae microspheres (Pae-MPs@OHA) to promote the healing of acute wounds in rats. The results demonstrated that the particle size of the Pae-MPs was 6.84 ± 0.51 μm, and the positive charge was 26.87 ± 1.51 mV. The uniform spherical structure of the Pae-MPs was observed by TEM. The Pae-MPs@OHA can maintain colloidal state in the range of 0.1–3.16 Hz. FTIR suggested that Pae could be effectively wrapped in MPs, and SEM indicated that the Pae-MPs@OHA had a uniform network pore structure. The Pae-MPs@OHA can realize the sustained release of Pae for 96 h. Biocompatibility experiments showed that the Pae-MPs@OHA hydrogels were safe and available. The Pae-MPs@OHA hydrogels can accelerate wound healing in rats. HE and masson staining suggested that the Pae-MPs@OHA could reduce inflammatory cell infiltration, promote re-epithelialization and collagen formation. The Pae-MPs@OHA could decrease the number of M1 and increase the number of M2 in macrophages, thus regulating the release of inflammatory factor TNF-α and IL-1β. The results of molecular docking and western blot results also confirmed that the Pae-MPs@OHA could reduce the expression of NF-κB, pNF-κB, NLRP3, ASC and pro-caspase-1. These findings suggest that the Pae-MPs@OHA has great potential for application in the treatment of inflammatory wound.

A drug-loaded nano chitosan/hyaluronic acid hydrogel system as a cartilage tissue engineering scaffold for drug delivery

Cartilage lesions, especially osteoarthritis (OA), usually arise from aging, trauma, or obesity and require medical intervention due to the damaged site's inflammation and the cartilage tissue's poor self-healing capacity. This study aimed to prepare a drug-loaded nanoparticle hydrogel system with anti-inflammatory and chondroprotective effects to treat OA. First, hyaluronic acid (HA) was oxidized to create aldehyde functional groups and then cross-linked with adipic acid dihydrazide (ADH) to form a hydrogel. Next, chitosan nanoparticles (CS NPs) loaded with an anti-inflammatory molecule (fisetin) and or a chondrogenic and chondroprotective agent (kartogenin) were incorporated into the hyaluronan hydrogel to improve the release profile of the drug and increase its retention time in the joint cavity. Incorporating drug-loaded NPs into the hyaluronan hydrogel provided the hydrogel with controlled release features and improved properties. In addition, the real-time PCR (Polymerase chain reaction) results showed that the hyaluronan hydrogel containing both drug-loaded NPs performed better than either constituent alone on an in vitro model of OA. Finally, based on the results of in vitro evaluation, this drug-loaded nanoparticle hydrogel system can be a promising technique for treating OA by rapidly suppressing inflammation and supporting cartilage regeneration and requires further investigation in an animal model of OA. Meanwhile, this study investigated, for the first time, the effect of the simultaneous use of fisetin and kartogenin together with a nano CS/HA hydrogel system to treat OA.

Biomimetic Triplet Messenger RNA Formulation in MXene Hydrogel Microneedles for Wound Healing

ABSTRACTMessenger RNA (mRNA) has demonstrated immense potential in disease therapeutic applications. The current direction is focused on imparting mRNA with competitive synthetic functions and delicate carrier systems. Here, inspired by the collaborative regulation of growth factors by the cellular microenvironment, we present novel transition metal carbide/nitride (MXene) hydrogel microneedles loaded with a biomimetic triplet mRNA formulation (TM) for diabetic wound treatment. Such microneedles were composed of TM, MXene, and hyaluronic acid hydrogel. The presence of MXene imparted the microneedles with great photo‐thermal responsiveness properties, thus realizing controlled active release by the shrinkage/swelling of hydrogel. With the effective release of TM, the microneedles were proven to enhance endothelial cell migration, growth, and angiogenesis. Through in vivo animal experiments, we have confirmed that TM‐microneedles (TM‐MNs) can promote tissue regeneration and collagen deposition more effectively than intravenous and intradermal administration. Thus, we believe that the proposed TM‐MN platform with precise delivery and controllable release of TM will show great potential for promoting the healing of clinic diabetic wounds.

Squeezable Hydrogel Microparticles for Single Extracellular Vesicle Protein Profiling.

Extracellular vesicles (EVs) are promising for molecular diagnostics, but current analyses are limited by the rarity and compositional heterogeneity of EV protein expression. Therefore, single EV profiling methods require high sensitivity, multiplexing, and throughput to address these issues. Here a single EV analysis technique that utilizes squeezable methacrylated hyaluronic acid hydrogel microparticles (MHPs) is described as a scaffold to immobilize EVs and perform an integrated rolling circle amplification (RCA) assay for an ultra-sensitive and multiplex analysis of single EV proteins. EVs are prepared into MHPs in a high-throughput manner with droplet microfluidics and optimally labeled with antibody-oligonucleotide conjugates in MHPs without steric limitations. By designing MHPs with high compressibility, single EV protein signals are amplified as RCA products that can be aligned on the same plane by physically squeezing MHPs and visualized with low magnification. This method provides a simple and scalable single EV imaging analysis pipeline for identifying multiplex marker expression patterns from single EVs. For validation, the single EV heterogeneity of highly expressed cancer cell markers is profiled across different cancer cell lines. These findings exemplify squeezable MHPs as a robust platform with high sensitivity, multiplexing, and scalability for resolving single EV heterogeneity and advancing molecular assay technologies.

Fabrication of Zinc(II) Mediated Poly(Acrylamide Co Acrylic Acid) Hydrogel with Thixotropic and Tribological Properties.

Hydrogels have emerged as promising candidates for biomedical applications, such as replacing natural articular cartilage, owing to their unique viscoelastic properties. However, sufficient mechanical properties, self-healing ability, and adhesive nature are some issues limiting its application window. Here, a facile one-pot synthesis of dual cross-linked zinc-coordinated copolymer hydrogels is presented. The network structure of the copolymer hydrogels is strategically developed via dynamic and reversible physical cross-linking by Zn2+ ions and simultaneous covalent cross-linking through a covalent cross-linker viz methylene bisacrylamide. Fourier-transform infrared (FTIR), X-ray diffraction (XRD) scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) analysis have thoroughly characterized the structure of the synthesized hydrogels. The introduction of Zn2+ offers dynamic and reversible complexation, leading to excellent mechanical properties and self-healing features. Moreover, the percentage of the equilibrium water content of zinc-coordinated copolymer hydrogel samples is comparable with that of natural articular cartilage. The Shear sliding study shows the dominant adhesive behavior of HGel-Zn(NO3)2 sample compared to the parent HGel sample. This facile dual cross-linked hydrogel, HGel-Zn(NO3)2, with a combination of good mechanical properties, efficient self-recovery, adequate water content, and favorable adhesive nature, seems very promising to mimic the articular cartilage.

Gene Therapy for Inflammatory Cascade in Intrauterine Injury with Engineered Extracellular Vesicles Hybrid Snail Mucus-enhanced Adhesive Hydrogels.

Early hyper-inflammation caused by intrauterine injury triggered subsequent intrauterine adhesion (IUA). STAT1-mediated M1 macrophages are confirmed to secrete pro-inflammatory cytokines to accelerate inflammatory cascade and IUA formation by multi-omics analysis and experimental verification. However, clinically used hyaluronic acid (HA) hydrogels are prone to slip out of injury sites due to poor bio-adhesion properties. Therefore, there are still challenges in applying hydrogels for M1 macrophage intervention in IUA treatment. Herein, an engineered extracellular vesicles (EVs) hybrid snail mucus (SM)-enhanced adhesive hydrogels to improve bio-adhesion property is fabricated and M1 macrophage intervention through targeting delivery and STAT1 silencing is achieved. First, inspired by the high bio-adhesion capacity of SM, SM and gelatin methacrylate (GelMA) solution are mixed to construct GelMA/SM (GS) hydrogel. Then, folic acid-modified extracellular vesicles (FA-EVs) are synthesized for targeting the delivery of STAT1-siRNA. Upon injection of FA-EVs hybrid GS hydrogel into the uterine cavity, a protective hydrogel layer forms on the surface of injury sites and sustains the release of STAT1-siRNA-loaded FA-EVs to curtail M1 macrophages generation through inhibiting STAT1 phosphorylation, resulting in reduction of myofibroblasts activation and collagen deposition. In addition, the pregnancy rate and the number of fetuses in rats treated with this hydrogel were much higher than those in other groups, suggesting that the hydrogel could promote functional endometrial regeneration and restore fertility. Overall, this study presents a promising strategy for employing FA-EVs hybrid adhesive hydrogel with superior bio-adhesion properties and M1 macrophage targeting delivery for IUA treatment and uterus recovery.

Water-Triboelectrification-Complemented Moisture Electric Generator.

Energy harvesting from ubiquitous natural water vapor based on moisture electric generator (MEG) technology holds great potential to power portable electronics, the Internet of Things, and wireless transmission. However, most devices still encounter challenges of low output, and a single MEG complemented with another form of energy harvesting for achieving high power has seldom been demonstrated. Herein, we report a flexible and efficient hybrid generator capable of harvesting moisture and tribo energies simultaneously, both from the source of water droplets. The moisture electric and triboelectric layers are based on a water-absorbent citric acid (CA)-mediated polyglutamic acid (PGA) hydrogel and porous electret expanded polytetrafluoroethylene (E-PTFE), respectively. Such a waterproof E-PTFE film not only enables efficient triboelectrification with water droplets' contact but also facilitates water vapor to be transferred into the hydrogel layer for moisture electricity generation. A single hybrid generator under water droplets' impact delivers a DC voltage of 0.55 V and a peak current density of 120 μA cm-2 from the MEG, together with a simultaneous AC output voltage of 300 V and a current of 400 μA from the complementary water-based triboelectric generator (TEG) side. Such a hybrid generator can work even under harsh wild environments with 5 °C cold and saltwater impacts. Significantly, an optical alarm and wireless communication system for wild, complex, and emergency scenarios is demonstrated with power from the hybrid generators. This work expands the applications of water-based electricity generation technologies and provides insight into harvesting multiple potential energies in the natural environment with high output.

Collaboration in Contradiction: Self-Adaptive Synergistic ROS Generation and Scavenge Balancing Strategies Used for the Infected Wounds Treatment.

The rational utilization of ROS is key to treating infected wounds. Exogenous ROS can destroy bacterial structures, quickly kill bacteria, and inhibit secondary infections. However, excess ROS at the wound will cause a secondary inflammatory response. Acute infections exacerbate this damage by increasing endogenous ROS, complicating the maintenance of ROS homeostasis. Therefore, regulating the balance of ROS production and scavenging in wounds has emerged as a promising strategy for wound treatment. Conventional ROS balancing platforms are mostly based on the " all for one" strategy of functional superposition and lack self-adaptability and integration. To subvert this conventional strategy, this study proposes a "one for all" self-adaptive integrated photodynamic therapy (PDT)-antioxidant model to actively regulate the ROS balance. A gelatin-hyaluronic acid hydrogel embedded with Se-modified cerium dioxide nanoparticles (Gel-HA-Se@CeO2 NPs) is designed for treating infected wounds. The Se@CeO2 NPs serve both as nanoenzymes and photosensitizers(PS). As nanoenzymes, they exhibit catalase and superoxide dismutase activities, converting hydrogen peroxide and superoxide anions into oxygen. As a PS, it synergizes with oxygen under NIR irradiation to rapidly produce singlet oxygen. Additionally, Se modification enhances the PDT effects by disrupting bacterial antioxidant systems. In vitro and in vivo experiments revealed that the ROS balance platform polarizes M1-type macrophages to M2-type macrophages, altering the wound microenvironment from proinflammatory to prohealing. RNA sequencing revealed that this hydrogel accelerated the reconstruction of the vascular network of the wound by activating the PI3K/AKT pathway and increasing VEGF secretion.This strategy is believed to be beneficial not only for infected wounds but also for treating other conditions that involve the regulation of reactive oxygen species, such as tumors and bacterial infections.

Application of Fluorescent Composite Materials as a Sustained Release System in Treatment of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disease characterized by oxidative stress and follicular dysfunction, leading to menstrual irregularities, hyperandrogenism, and infertility. Traditional drug delivery methods often result in drug loss and side effects on normal tissues. To address these issues, we synthesized two novel Co(II)-containing coordination polymers (CPs), {[Co(L)(H2O)2]·2H2O}n (1) and {[Co(L)(H2O)2]·1.5H2O}n (2), through the reaction of the T-shaped ligand (4 - 3'-pyridyl-,6 - 4'-carboxylphenyl)picolinic acid (H2L) with Co(NO3)2·6H2O via a solvothermal process. Fluorescence spectroscopy revealed that the fluorescence emission of the CPs originates from the ligand, indicating their potential application as blue fluorescence materials. Subsequently, we encapsulated these CPs with hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) hydrogels to create two types of metal gel particles carrying spironolactone (HA/CMCS-CPs@spironolactone). SEM and TEM analyses showed that the material consists of tightly stacked sheet-like structures with an average size of approximately 100nm. Thermogravimetric analysis (TGA) indicated that the material begins to decompose at around 115°C, demonstrating good thermal stability. We assessed the inhibitory effects of these materials on oxidative stress induced by PCOS. The results showed that both types of spironolactone-loaded metal gel particles significantly reduced malondialdehyde (MDA) levels, particularly the particles constructed with CP2. HA/CMCS-CP1@spironolactone reduced MDA levels by approximately 17% and 46% at low and high concentrations, respectively, while HA/CMCS-CP2@spironolactone decreased MDA levels by about 55% and 39% at high and low concentrations, respectively. Therefore, the novel drug delivery system reported in this study has the potential to become a safe and effective option for the localized treatment of PCOS.

The e-Flower: A hydrogel-actuated 3D MEA for brain spheroid electrophysiology.

Traditional microelectrode arrays (MEAs) are limited to measuring electrophysiological activity in two dimensions, failing to capture the complexity of three-dimensional (3D) tissues such as neural organoids and spheroids. Here, we introduce a flower-shaped MEA (e-Flower) that can envelop submillimeter brain spheroids following actuation by the sole addition of the cell culture medium. Inspired by soft microgrippers, its actuation mechanism leverages the swelling properties of a polyacrylic acid hydrogel grafted to a polyimide substrate hosting the electrical interconnects. Compatible with standard electrophysiology recording systems, the e-Flower does not require additional equipment or solvents and is ready to use with preformed 3D tissues. We designed an e-Flower achieving a curvature as low as 300 micrometers within minutes, a value tunable by the choice of reswelling media and hydrogel cross-linker concentration. Furthermore, we demonstrate the ability of the e-Flower to detect spontaneous neural activity across the spheroid surface, demonstrating its potential for comprehensive neural signal recording.