Immobilization of laccase on magnetic PEGDA-CS inverse opal hydrogel for enhancement of bisphenol A degradation in aqueous solution.

Endocrine disruptors such as bisphenol A (BPA) adversely affect the environment and human health. Laccases are used for the efficient biodegradation of various persistent organic pollutants in an environmentally safe manner. However, the direct application of free laccases is generally hindered by short enzyme lifetimes, non-reusability, and the high cost of a single use. In this study, laccases were immobilized on a novel magnetic three-dimensional poly(ethylene glycol) diacrylate (PEGDA)-chitosan (CS) inverse opal hydrogel (LAC@MPEGDA@CS@IOH). The immobilized laccase showed significant improvement in the BPA degradation performance and superior storage stability compared with the free laccase. 91.1% of 100 mg/L BPA was removed by the LAC@MPEGDA@CS@IOH in 3 hr, whereas only 50.6% of BPA was removed by the same amount of the free laccase. Compared with the laccase, the outstanding BPA degradation efficiency of the LAC@MPEGDA@CS@IOH was maintained over a wider range of pH values and temperatures. Moreover, its relative activity of was maintained at 70.4% after 10 cycles, and the system performed well in actual water matrices. This efficient method for preparing immobilized laccases is simple and green, and it can be used to further develop ecofriendly biocatalysts to remove organic pollutants from wastewater.

Cryopreserved nanostructured fibrin-agarose hydrogels are efficient and safe hemostatic agents.

Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.

[Bacterial Blocking and Repair of Intestinal Defects With Well-Alighed Lamellar MXene/Polyvinyl Alcohol Hydrogels Prepared by Bidirectional Freezing Method]. / 双向冷冻法制备的取向多层MXene/PVAæ°´å‡èƒ¶çš„ç»†èŒå±è”½ä½œç”¨åŠå¯¹è‚ é“ç¼ºæŸçš„ä¿®å¤.

Objective: To explore the bacterial blocking effect of oriented multilayer MXene/polyvinyl alcohol (PVA) nanocomposite hydrogels and their effect on the repair of intestinal defects. Methods: MXene/PVA nanocomposite hydrogels were prepared using the traditional freezing method and the bidirectional freezing ice template method. The structures of the different hydrogels were observed using scanning electron microscopy (SEM) and micro-CT reconstruction. The rheological properties of the hydrogels were measured using a dynamic rheometer, and their mechanical properties were assessed using a universal testing machine. The burst pressure of the hydrogels was determined through burst experiments, and bacterial colony growth was observed by the osmosis method to assess the bacteria blocking ability of the hydrogels in vitro. A rat model of cecal perforation was established, and the hydrogels were used for intestinal repair. Gram staining was performed to observe in vivo the bacterial blocking ability of the hydrogels, HE staining was performed to observe the intestinal inflammation, and CD31 and CD68 immunofluorescence staining and proliferating cell nuclear antigen (PCNA) staining were performed to observe the repair effect of the hydrogels on intestinal defects. Results: SEM and micro-CT reconstruction revealed that the hydrogel prepared by the traditional freezing method exhibited a random porous structure, while the hydrogel prepared by the bidirectional freezing method showed an oriented multilayer structure. Rheological and tensile tests indicated that the oriented hydrogel had superior mechanical properties, and the burst pressure of the oriented multilayer hydrogel was as high as 27 kPa, significantly higher than that of the non-oriented hydrogel (P<0.001). Bacterial colony growth was observed by the osmosis method and it was found that, compared with the non-oriented hydrogel, the oriented multilayer hydrogel could effectively prevent the infiltration of Escherichia coli and Staphylococcus aureus in vitro. Gram staining results showed that the oriented multilayer hydrogel could effectively block intestinal bacteria from entering the abdominal cavity in vivo. HE staining results showed that the oriented multilayer hydrogel could effectively reduce intestinal inflammation in vivo. CD31 and CD68 immunofluorescence staining and PCNA staining results showed that the oriented multilayer hydrogel had a repairing effect on intestinal defects in vivo. Conclusion: The oriented multilayer hydrogel prepared by bidirectional freezing effectively prevents bacterial infiltration and reduces intestinal inflammation.

In situ formed aldehyde-modified hyaluronic acid hydrogel with polyelectrolyte complexes of aldehyde-modified chondroitin sulfate and gelatin: An approach for minocycline delivery.

Polysaccharides like hyaluronan (HA) and chondroitin sulfate (CS) are native of the brain's extracellular matrix crucial for myelination and brain maturation. Despite extensive research on HA and CS as drug delivery systems (DDS), their high water solubility limits their application as drug carriers. This study introduces an injectable DDS using aldehyde-modified hyaluronic acid (HAOX) hydrogel containing polyelectrolyte complexes (PEC) formed with calcium, gelatin, and either CS or aldehyde-modified CS (CSOX) to deliver minocycline for Multiple Sclerosis therapy. PECs with CSOX enable covalent crosslinking to HAOX, creating immobilized PECs (HAOX_PECOX), while those with CS remain unbound (HAOX_PECS). The in situ forming DDS can be administered via a 20 G needle, with rapid gelation preventing premature leakage. The system integrates into an implanted device for minocycline release through either Fickian or anomalous diffusion, depending on PEC immobilization. HAOX_PECOX reduced burst release by 88 %, with a duration of 127 h for 50 % release. The DDS exhibited an elastic modulus of 3800 Pa and a low swelling ratio (0-1 %), enabling precise control of minocycline release kinetics. Released minocycline reduced IL-6 secretion in the Whole Blood Monocytes Activation Test, suggesting that DDS formation may not alter the biological activity of the loaded drug.

Visual tracking of real-time freshness of fish using an agar hydrogel colorimetric indicator containing CuNPs/NCQDs.

A simple, selective, and affordable dual fluorescence-colorimetric indicator for hydrogen sulfide was developed based on a complex of copper nanoparticles and N-doped carbon quantum dots (CuNPs/NCQDs). Real-time and visual freshness tracking of fish was done using a colorimetric indicator by incorporating CuNPs/NCQDs into agar hydrogel (AH-CuNPs/NCQDs). The fluorescence response of the CuNPs/NCQDs solution is quenched upon exposure to H2S. The field-emission scanning electron microscopy image of the AH-CuNPs/NCQDs film revealed a unified structure. The prepared indicator exhibited a good and irreversible response to H2S, with a LOD of 91.36 and a LOQ of 276.86 µM, based on the localized surface plasmon resonance (LSPR) mechanism. The X-ray photoelectron spectrometer and Fourier transform infrared spectrometer results confirmed the formation of a CuS bond in the colorimetric indicator exposed to fish spoilage. The prepared indicator demonstrated good stability and remained unaffected by pH or other volatile compounds. Notably, there was a strong correlation between ΔΕ and fish freshness parameters (pH, TV-BN, and TVC). Light green, pale yellow, and dark yellow colors, respectively, indicated freshness, semi-freshness, and spoilage of fish during storage in the refrigerator. Overall, the prepared indicator can be effectively used for detecting spoilage in meat products as a highly sensitive freshness indicator.

Absorption enhancement strategies in chitosan-based nanosystems and hydrogels intended for ocular delivery: Latest advances for optimization of drug permeation.

Ophthalmic diseases can be presented as acute diseases like allergies, ocular infections, etc., or chronic ones that can be manifested as a result of systemic disorders, like diabetes mellitus, thyroid, rheumatic disorders, and others. Chitosan (CS) and its derivatives have been widely investigated as nanocarriers in the delivery of drugs, genes, and many biological products. The biocompatibility and biodegradability of CS made it a good candidate for ocular delivery of many ingredients, including immunomodulating agents, antibiotics, ocular hypertension medications, etc. CS-based nanosystems have been successfully reported to modulate ocular diseases by penetrating biological ocular barriers and targeting and controlling drug release. This review provides guidance to drug delivery formulators on the most recently published strategies that can enhance drug permeation to the ocular tissues in CS-based nanosystems, thus improving therapeutic effects through enhancing drug bioavailability. This review will highlight the main ocular barriers to drug delivery observed in the nano-delivery system. In addition, the CS physicochemical properties that contribute to formulation aspects are discussed. It also categorized the permeation enhancement strategies that can be optimized in CS-based nanosystems into four aspects: CS-related physicochemical properties, formulation components, fabrication conditions, and adopting a novel delivery system like implants, inserts, etc. as described in the published literature within the last ten years. Finally, challenges encountered in CS-based nanosystems and future perspectives are mentioned.

An injectable self-healing alginate hydrogel with desirable mechanical and degradation properties for enhancing osteochondral regeneration.

Articular cartilage and subchondral bone defects have always been problematic because the osteochondral tissue plays a crucial role in the movement of the body and does not recover spontaneously. Here, an injectable hydrogel composed of oxidized sodium alginate/gelatin/chondroitin sulfate (OSAGC) was designed for the minimally invasive treatment and promotion of osteochondral regeneration. The OSAGC hydrogel had a double network based on dynamic covalent bonds, demonstrating commendable injectability and self-healing properties. Chondroitin sulfate was organically bound to the hydrogel network, retaining its own activity and gradually releasing during the degradation process as well as improving mechanical properties. The compressive strength could be increased up to 3 MPa by regulating the concentration of chondroitin sulphate and the oxidation level, and this mechanical stimulation could help repair injured tissue. The OSAGC hydrogel had a favourable affinity to articular cartilage and was able to release active ingredients in a sustained manner over 3 months. The OSAGC showed no cytotoxic effects. Results from animal studies demonstrated its capacity to regenerate new bone tissue in four weeks and new cartilage tissue in twelve weeks. The OSAGC hydrogel represented a promising approach to simplify bone surgery and repair damaged osteochondral tissue.

Tunicate cellulose nanocrystals strengthened injectable stretchable hydrogel as multi-responsive enhanced antibacterial wound dressing for promoting diabetic wound healing.

The intricate microenvironment of diabetic wounds characterized by hyperglycemia, intense oxidative stress, persistent bacterial infection and complex pH fluctuations hinders the healing process. Herein, an injectable multifunctional hydrogel (QPTx) was developed, which exhibited excellent mechanical performance and triple responsiveness to pH, temperature, and glucose due to dynamic covalent cross-linking involving dynamic Schiff base bonds and phenylboronate esters with phenylboronic-modified quaternized chitosan (QCS-PBA), polydopamine coated tunicate cellulose crystals (PDAn@TCNCs) and polyvinyl alcohol (PVA). Furthermore, the hydrogels can incorporate insulin (INS) drugs to adapt to the complex and variable wound environment in diabetic patients for on-demand drug release that promote diabetic wound healing. Based on various excellent properties of the colloidal materials, the hydrogels were evaluated for self-healing, rheological and mechanical properties, in vitro insulin response to pH/temperature/glucose release, antibacterial, antioxidant, tissue adhesion, coagulation, hemostasis in vivo and in vitro, and biocompatibility and biodegradability. By introducing PDAn@TCNCs particles, the hydrogel has photothermal antibacterial activity, enhanced adhesion and oxidation resistance. We further demonstrated that these hydrogel dressings significantly improved the healing process compared to commercial dressings (Tegaderm™) in full-layer skin defect models. All indicated that the glucose-responsive QPTx hydrogel platform has great potential for treating diabetic wounds.

The influence of the pectin structure on the properties of hydrogel dressings doped with octenidine-containing antiseptic.

This article presents a method for producing hydrogel dressings using high methylated pectin from apples or citrus, doped with the antiseptic agent, octenidine dihydrochloride. Octenidine was incorporated in-situ during the polymer crosslinking. The pectins were characterized by their varying molecular weight characteristics, monosaccharide composition, and degree of esterification (DE). The study assessed the feasibility of producing biologically active hydrogels with pectin and delved into how the polymer's characteristics affect the properties of the resulting dressings. The structure evaluation of hydrogel materials showed interactions between individual components of the system and their dependence on the type of used pectin. Both the antimicrobial properties and cytotoxicity of the dressings were evaluated. The results suggest that the primary determinants of the functional attributes of the hydrogels are the molecular weight characteristics and the DE of the pectin. As these values rise, there is an increase in polymer-polymer interactions, overshadowing polymer-additive interactions. This intensification strengthens the mechanical and thermal stability of the hydrogels and enhances the release of active components into the surrounding environment. Biological evaluations demonstrated the ability of octenidine to be released from the dressings and effectively inhibit the growth of microbial pathogens.

Sealing the Pandora's vase of pancreatic fistula through entrapping the digestive enzymes within a dextrorotary (D)-peptide hydrogel.

A variety of therapeutic possibilities have emerged for skillfully regulating protein function or conformation through intermolecular interaction modulation to rectify abnormal biochemical reactions in diseases. Herein, a devised strategy of enzyme coordinators has been employed to alleviate postoperative pancreatic fistula (POPF), which is characterized by the leakage of digestive enzymes including trypsin, chymotrypsin, and lipase. The development of a dextrorotary (D)-peptide supramolecular gel (CP-CNDS) under this notion showcases its propensity for forming gels driven by intermolecular interaction. Upon POPF, CP-CNDS not only captures enzymes from solution into hydrogel, but also effectively entraps them within the internal gel, preventing their exchange with counterparts in the external milieu. As a result, CP-CNDS completely suppresses the activity of digestive enzymes, effectively alleviating POPF. Remarkably, rats with POPF treated with CP-CNDS not only survived but also made a recovery within a mere 3-day period, while mock-treated POPF rats had a survival rate of less than 5 days when experiencing postoperative pancreatic fistula, leak or abscess. Collectively, the reported CP-CNDS provides promising avenues for preventing and treating POPF, while exemplifying precision medicine-guided regulation of protein activity that effectively targets specific pathogenic molecules across multiple diseases.

The use of hyaluronic acid in a 3D biomimetic scaffold supports spheroid formation and the culture of cancer stem cells.

Three-dimensional (3D) bioprinting culture models capable of reproducing the pathological architecture of diseases are increasingly advancing. In this study, 3D scaffolds were created using extrusion-based bioprinting method with alginate, gelatin, and hyaluronic acid to investigate the effects of hyaluronic acid on the physical properties of the bioscaffold as well as on the formation of liver cancer spheroids. Conformational analysis, rheological characterization, and swelling-degradation tests were performed to characterize the scaffolds. After generating spheroids from hepatocellular carcinoma cells on the 3D scaffolds, cell viability and proliferation assays were performed. Flow cytometry and immunofluorescence microscopy were used into examine the expression of albumin, CD44, and E-cadherin to demonstrate functional capability and maturation levels of the spheroid-forming cells. The results show that hyaluronic acid in the scaffolds correlates with spheroid formation and provides high survival rates. It is also associated with an increase in CD44 expression and a decrease in E-cadherin, while there is no significant change in the albumin expression in the cells. Overall, the findings demonstrate that hyaluronic acid in a 3D hydrogel scaffold supports spheroid formation and may induce stemness. We present a promising 3D scaffold model for enhancing liver cancer spheroid formation and mimicking solid tumors. This model also has the potential for further studies to examine stem cell properties in 3D models.

Radiation synthesis of sodium alginate/gelatin based ultra-absorbent hydrogel for efficient water and nitrogen management in wheat under drought stress.

The main focus of this study was on using radiation to make an ultra-absorbent hydrogel (UAH) from sodium alginate (SA) and gelatin (GL) biopolymers. This UAH can effectively handle water and nitrogen in wheat farming during drought stress. The hydrogel was synthesized by gamma irradiation-induced SA/GL/polyacrylamide crosslinking at 10-40 kGy. Varying SA/GL ratios affected swelling and the gel fraction of SA/GL/PAm hydrogels. The (SA/GL 17/83) hydrogel exhibited a 40.03 g/g swelling degree, while increasing SA content resulted in higher swelling, peaking at 75.5 g/g for (SA/GL 83/17). This indicated a synergistic interaction between SA and GL. The gel fraction also increased from 76.8 to 90.3%, with a higher GL content reflecting increased crosslinking. After multiple hydrolysis cycles, the hydrogel achieved 1293 (g/g) swelling and 36 days of water retention. When applied to wheat (Triticuma estivum) under drought stress, it significantly improved shoot length (18%), root length (43%), shoot fresh weight (49%), and shoot dry weight (51%) under extreme drought. The significant increases in protein and carbohydrate content in both shoots (up to 32% and 19%, respectively) and grains (up to 21% and 24%, respectively), along with the reduction in proline content (up to 38%), demonstrate that ultra-absorbent hydrogel (UAH) effectively enhances nitrogen content, photosynthesis, and overall plant health in wheat under varying drought stress levels. This novel SA/GL-based UAH holds promise for addressing water scarcity and agricultural challenges, offering a sustainable solution for water and nitrogen management under drought stress.

Crosslinked-hybrid nanoparticle embedded in thermogel for sustained co-delivery to inner ear.

Treatment-induced ototoxicity and accompanying hearing loss are a great concern associated with chemotherapeutic or antibiotic drug regimens. Thus, prophylactic cure or early treatment is desirable by local delivery to the inner ear. In this study, we examined a novel way of intratympanically delivered sustained nanoformulation by using crosslinked hybrid nanoparticle (cHy-NPs) in a thermoresponsive hydrogel i.e. thermogel that can potentially provide a safe and effective treatment towards the treatment-induced or drug-induced ototoxicity. The prophylactic treatment of the ototoxicity can be achieved by using two therapeutic molecules, Flunarizine (FL: T-type calcium channel blocker) and Honokiol (HK: antioxidant) co-encapsulated in the same delivery system. Here we investigated, FL and HK as cytoprotective molecules against cisplatin-induced toxic effects in the House Ear Institute - Organ of Corti 1 (HEI-OC1) cells and in vivo assessments on the neuromast hair cell protection in the zebrafish lateral line. We observed that cytotoxic protective effect can be enhanced by using FL and HK in combination and developing a robust drug delivery formulation. Therefore, FL-and HK-loaded crosslinked hybrid nanoparticles (FL-cHy-NPs and HK-cHy-NPs) were synthesized using a quality-by-design approach (QbD) in which design of experiment-central composite design (DoE-CCD) following the standard least-square model was used for nanoformulation optimization. The physicochemical characterization of FL and HK loaded-NPs suggested the successful synthesis of spherical NPs with polydispersity index < 0.3, drugs encapsulation (> 75%), drugs loading (~ 10%), stability (> 2 months) in the neutral solution, and appropriate cryoprotectant selection. We assessed caspase 3/7 apopototic pathway in vitro that showed significantly reduced signals of caspase 3/7 activation after the FL-cHy-NPs and HK-cHy-NPs (alone or in combination) compared to the CisPt. The final formulation i.e. crosslinked-hybrid-nanoparticle-embedded-in-thermogel was developed by incorporating drug-loaded cHy-NPs in poloxamer-407, poloxamer-188, and carbomer-940-based hydrogel. A combination of artificial intelligence (AI)-based qualitative and quantitative image analysis determined the particle size and distribution throughout the visible segment. The developed formulation was able to release the FL and HK for at least a month. Overall, a highly stable nanoformulation was successfully developed for combating treatment-induced or drug-induced ototoxicity via local administration to the inner ear.

An afferent nerve-like electronic device with somatic mechanical perception and sensation management.

Tactile and pain perception are essential for biological skin to interact with the external environment. This complex interplay of sensations allows for the detection of potential threats and appropriate responses to stimuli. However, the challenge is to enable flexible electronics to respond to mechanical stimuli such as biological skin, and researchers have not clearly reported the successful integration of somatic mechanical perception and sensation management functions into neuro-like electronics. In this work, an afferent nerve-like device with a pressure sensor and a perception management module is proposed. The pressure sensor comprises two conductive fabric layers and an ionic hydrogel, forming a capacitor structure that emulates the swift transition from tactile to pain perception under mechanical stimulation. Drawing inspiration from the neuronal "gate control" mechanism, the sensation management module adjusts signals in response to rubbing, accelerating the discharge process and reducing the perception duration, thereby replicating the inhibitory effect of biological neurons on pain following tactile interference. This integrated device, encompassing somatic mechanical perception and sensation management, holds promise for applications in soft robotics, prosthetics, and human-machine interaction.

Photo-programmable hydrogel iontronics for electrically and chromatically rewritable circuits.

Hydrogel-based iontronics is emerging as a promising frontier in healthcare and human-machine interfacing (HMI), offering excellent compatibility with biological systems in terms of electrical, chemical, and mechanical properties. However, conventional hydrogel systems have limitations in dynamically regulating their electrical and optical properties, which restricts their use in adaptive electronics and responsive interfaces. In this study, we present a new hydrogel system with UV photochemistry-induced reversible conductivity, enabling reversible changes in conductivity. Unlike typical photo-responsive hydrogels that revert to their original states upon removal of the light source, the new hydrogel can maintain its activated states without continuous light exposure, facilitating practical applications. By leveraging the photobase triphenylmethane leucohydroxide and photoacid n-nitrobenzaldehyde, we achieve a significant increase in photo-induced conductivity compared to existing photo-ionic hydrogels. Combining the effective photo-induced conductivity and the accompanied photochromatic effect, we demonstrate a full hydrogel-based stylus pad capable of tracking motion and strokes, and a soft calculator keypad with programmable conductivity and imprinted patterns. These advancements underscore the importance of actively controlling localized conductivity and processing light inputs in hydrogels, exhibiting their potential for diverse applications in bioelectronics and HMI.

A thermo-sensitive hydrogel with prominent hemostatic effect prevents tumor recurrence via anti-anoikis-resistance.

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell-cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery.

Tissue-scale in vitro epithelial wrinkling and wrinkle-to-fold transition.

Although epithelial folding is commonly studied using in vivo animal models, such models exhibit critical limitations in terms of real-time observation and independent control of experimental parameters. Here, we develop a tissue-scale in vitro epithelial bilayer folding model that incorporates an epithelium and extracellular matrix (ECM) hydrogel, thereby emulating various folding structures found in in vivo epithelial tissue. Beyond mere folding, our in vitro model realizes a hierarchical transition in the epithelial bilayer, shifting from periodic wrinkles to a single deep fold under compression. Experimental and theoretical investigations of the in vitro model imply that both the strain-stiffening of epithelium and the poroelasticity of ECM influence the folded structures of epithelial tissue. The proposed in vitro model will aid in investigating the underlying mechanism of tissue-scale in vivo epithelial folding relevant to developmental biology and tissue engineering.

Advancing osteoarthritis therapy with GMOCS hydrogel-loaded BMSCs-exos.

This study investigated the mechanism of the extracellular matrix-mimicking hydrogel-mediated TGFB1/Nrf2 signaling pathway in osteoarthritis using bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos). A GMOCS-Exos hydrogel was synthesized and evaluated for its impact on chondrocyte viability and neutrophil extracellular traps (NETs) formation. In an OA rat model, GMOCS-Exos promoted cartilage regeneration and inhibited NETs formation. Transcriptome sequencing identified TGFB1 as a key gene, with GMOCS-Exos activating Nrf2 signaling through TGFB1. Depletion of TGFB1 hindered the cartilage-protective effect of GMOCS-Exos. This study sheds light on a promising therapeutic strategy for osteoarthritis through GMOCS-Exos-mediated TGFB1/Nrf2 pathway modulation.

GO/Cu Nanosheet-Integrated Hydrogel Platform as a Bioactive and Biocompatible Scaffold for Enhanced Calvarial Bone Regeneration.

Purpose: The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects. Herein, an innovative bone scaffold consisting of GO/Cu nanoderivatives and GelMA-based organic-inorganic hybrids was reported for repairing full-thickness calvarial bone defect. Methods: In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility, macrophage polarization and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models (BALB/c mice and SD rats) were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential. Results: We found that GO/Cu-functionalized GelMA/ß-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities, M2 type macrophage polarization, increased secretion of anti-inflammatory factors and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu2+. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds demonstrated significantly increased bone morphometric values and newly formed bone tissues, indicating accelerated bone healing. Conclusion: Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite-incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, with the optimization of material properties and biosafety, it thereby demonstrates great application potential for correcting craniofacial bone defects in future clinical scenarios.