Guanosine hydrogels in focus: A comprehensive analysis through mid-infrared spectroscopy.

Guanosine nucleosides and nucleotides have the peculiar ability to self-assemble in water to form supramolecular complex architectures from G-quartets to G-quadruplexes. G-quadruplexes exhibit in turn a large liquid crystalline lyotropic polymorphism, but they eventually cross-link or entangle to form a densely connected 3D network (a molecular hydrogel), able to entrap very large amount of water (up to the 99% v/v). This high water content of the hydrogels enables tunable softness, deformability, self-healing, and quasi-liquid properties, making them ideal candidates for different biotechnological and biomedical applications. In order to fully exploit their possible applications, Attenuated Total Reflection-Fourier Transform InfraRed (ATR-FTIR) spectroscopy was used to unravel the vibrational characteristics of supramolecular guanosine structures. First, the characteristic vibrations of the known quadruplex structure of guanosine 5'-monophosphate, potassium salt (GMP/K), were investigated: the identified peaks reflected both the chemical composition of the sample and the formation of quartets, octamers, and quadruplexes. Second, the role of K+ and Na+ cations in promoting the quadruplex formation was assessed: infrared spectra confirmed that both cations induce the formation of G-quadruplexes and that GMP/K is more stable in the G-quadruplex organization. Finally, ATR-FTIR spectroscopy was used to investigate binary mixtures of guanosine (Gua) and GMP/K or GMP/Na, both systems forming G-hydrogels. The same G-quadruplex-based structure was found in both mixtures, but the proportion of Gua and GMP affected some features, like sugar puckering, guanine vibrations, and base stacking, reflecting the known side-to-side aggregation and bundle formation occurring in these binary systems.

Advancements in hydrogel design for articular cartilage regeneration: A comprehensive review.

This review paper explores the cutting-edge advancements in hydrogel design for articular cartilage regeneration (CR). Articular cartilage (AC) defects are a common occurrence worldwide that can lead to joint breakdown at a later stage of the disease, necessitating immediate intervention to prevent progressive degeneration of cartilage. Decades of research into the biomedical applications of hydrogels have revealed their tremendous potential, particularly in soft tissue engineering, including CR. Hydrogels are highly tunable and can be designed to meet the key criteria needed for a template in CR. This paper aims to identify those criteria, including the hydrogel components, mechanical properties, biodegradability, structural design, and integration capability with the adjacent native tissue and delves into the benefits that CR can obtain through appropriate design. Stratified-structural hydrogels that emulate the native cartilage structure, as well as the impact of environmental stimuli on the regeneration outcome, have also been discussed. By examining recent advances and emerging techniques, this paper offers valuable insights into developing effective hydrogel-based therapies for AC repair.

Immune-modulative nano-gel-nano system for patient-favorable cancer therapy.

Current cancer immunotherapies exhibit low response rates attributed to suppressive tumor immune microenvironments (TIMEs). To address these unfavorable TIMEs, supplementation with tumor-associated antigens and stimulation of immune cells at target sites are indispensable for eliciting anti-tumoral immune responses. Previous research has explored the induction of immunotherapy through multiple injections and implants; however, these approaches lack consideration for patient convenience and the implementation of finely tunable immune response control systems to mitigate the side effects of over-inflammatory responses, such as cytokine storms. In this context, we describe a patient-centric nano-gel-nano system capable of sustained generation of tumor-associated antigens and release of adjuvants. This is achieved through the specific delivery of drugs to cancer cells and antigens/adjuvants to immune cells over the long term, maintaining proper concentrations within the tumor site with a single injection. This system demonstrates local immunity against tumors with a single injection, enhances the therapeutic efficacy of immune checkpoint blockades, and induces systemic and memory T cell responses, thus minimizing systemic side effects.

Obtaining and characterization of natural extracts from mango (Mangifera Indica) peel and its effect on the rheological behavior in new mango kernel starch hydrogels.

Hydrogels based on natural polymers have aroused interest from the scientific community. The aim of this investigation was to obtain natural extracts from mango peels and to evaluate their addition (1, 3, and 5%) on the rheological behavior of mango starch hydrogels. The total phenolic content, antioxidant activities, and phenolic acid profile of the natural extracts were evaluated. The viscoelastic and thixotropic behavior of hydrogels with the addition of natural extracts was evaluated. The total phenol content and antioxidant activity of the extracts increased significantly (p<0.05) with the variation of the ethanol-water ratio; the phenolic acid profile showed the contain of p-coumaric, ellagic, ferulic, chlorogenic acids, epicatechein, catechin, querecetin, and mangiferin. The viscoelastic behavior of the hydrogels showed that the storage modulus G' is larger than the loss modulus G'' indicating a viscoelastic solid behavior. The addition of extract improved the thermal stability of the hydrogels. 1% of the extracts increase viscoelastic and thixotropic properties, while concentrations of 3 to 5% decreased. The recovery percentage (%Re) decreases at concentrations from 0% to 1% of natural extracts, however, at concentrations from 3% to 5% increased.

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.

Local delivery of carboplatin-loaded hydrogel and calcium carbonate enables two-stage drug release for limited-dose radiation to eliminate mouse malignant glioma.

Postoperative radiotherapy remains the gold standard for malignant glioma treatment. Clinical limitations, including tumor growth between surgery and radiotherapy and the emergence of radioresistance, reduce treatment effectiveness and result in local disease progression. This study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy. We developed a compound of carboplatin-loaded hydrogel (CPH) incorporated with carboplatin-loaded calcium carbonate (CPCC) to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model. The doses of carboplatin in CPH and CPCC treatments were 150 µL (carboplatin concentration of 5 mg/mL) and 15 mg (carboplatin concentration of 4.1 µg/mg), respectively. Mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation. Local CPH-CPCC delivery synergized effectively with limited-dose radiation to eliminate mouse glioma, offering a promising solution for overcoming clinical limitations.

Orchestrated metal-coordinated carrier-free celastrol hydrogel intensifies T cell activation and regulates response to immune checkpoint blockade for synergistic chemo-immunotherapy.

The challenges generated by insufficient T cell activation and infiltration have constrained the application of immunotherapy. Making matters worse, the complex tumor microenvironment (TME), resistance to apoptosis collectively poses obstacles for cancer treatment. The carrier-free small molecular self-assembly strategy is a current research hotspot to overcome these challenges. This strategy can transform multiple functional agents into sustain-released hydrogel without the addition of any excipients. Herein, a coordination and hydrogen bond mediated tricomponent hydrogel (Cel hydrogel) composed of glycyrrhizic acid (GA), copper ions (Cu2+) and celastrol (Cel) was initially constructed. The hydrogel can regulate TME by chemo-dynamic therapy (CDT), which increases reactive oxygen species (ROS) in conjunction with GA and Cel, synergistically expediting cellular apoptosis. What's more, copper induced cuproptosis also contributes to the anti-tumor effect. In terms of regulating immunity, ROS generated by Cel hydrogel can polarize tumor-associated macrophages (TAMs) into M1-TAMs, Cel can induce T cell proliferation as well as activate DC mediated antigen presentation, which subsequently induce T cell proliferation, elevate T cell infiltration and enhance the specific killing of tumor cells, along with the upregulation of PD-L1 expression. Upon co-administration with aPD-L1, this synergy mitigated both primary and metastasis tumors, showing promising clinical translational value.

A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Bioactive nanocomposite hydrogel enhances postoperative immunotherapy and bone reconstruction for osteosarcoma treatment.

Osteosarcoma, a malignant bone tumor often characterized by high hedgehog signaling activity, residual tumor cells, and substantial bone defects, poses significant challenges to both treatment response and postsurgical recovery. Here, we developed a nanocomposite hydrogel for the sustained co-delivery of bioactive magnesium ions, anti-PD-L1 antibody (αPD-L1), and hedgehog pathway antagonist vismodegib, to eradicate residual tumor cells while promoting bone regeneration post-surgery. In a mouse model of tibia osteosarcoma, this hydrogel-mediated combination therapy led to remarkable tumor growth inhibition and hence increased animal survival by enhancing the activity of tumor-suppressed CD8+ T cells. Meanwhile, the implanted hydrogel improved the microenvironment of osteogenesis through long-term sustained release of Mg2+, facilitating bone defect repair by upregulating the expression of osteogenic genes. After 21 days, the expression levels of ALP, COL1, RUNX2, and BGLAP in the Vis-αPD-L1-Gel group were approximately 4.1, 5.1, 5.5, and 3.4 times higher than those of the control, respectively. We believe that this hydrogel-based combination therapy offers a potentially valuable strategy for treating osteosarcoma and addressing the tumor-related complex bone diseases.

Mitochondrial 'Birth-Death' coordinator: An intelligent hydrogen nanogenerator to enhance intervertebral disc regeneration.

Currently, mitochondrial dysfunction caused by oxidative stress is a growing concern in degenerative diseases, notably intervertebral disc degeneration (IVDD). Dysregulation of the balance of mitochondrial quality control (MQC) has been considered the key contributor, while it's still challenging to effectively harmonize different MQC components in a simple and biologically safe way. Hydrogen gas (H2) is a promising mitochondrial therapeutic molecule due to its bio-reductivity and diffusibility across cellular membranes, yet its relationship with MQC regulation remains unknown. Herein, we propose a mitochondrial 'Birth-Death' coordinator achieved by an intelligent hydrogen nanogenerator (Fe@HP-OD), which can sustainably release H2 in response to the unique microenvironment in degenerated IVDs. Both in vitro and in vivo results prove alleviation of cellular oxidative stress and restoration of nucleus pulposus cells function, thereby facilitating successful IVD regeneration. Significantly, this study for the first time proposes the mitochondrial 'Birth-Death' coordination mechanism: 1) attenuation of overactivated mitochondrial 'Death' process (UPRmt and unselective mitophagy); and 2) activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial 'Birth-Death' balance (mitochondrial biogenesis and controlled mitophagy). These pioneering findings can fill in the gaps in molecular mechanisms for H2 regulation on MQC homeostasis, and pave the way for future strategies towards restoring equilibrium of MQC system against degenerative diseases.

Enhancing miR-19a/b induced cardiomyocyte proliferation in infarcted hearts by alleviating oxidant stress and controlling miR-19 release.

Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that ∼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.

A harsh environmental resistant and long-term stable ionic conductive hydrogel by one-step preparation for wireless health activity and physiological state detection.

Benefiting from the good electromechanical performance, ionic conductive hydrogel can easily convert the deformation into electrical signals, showing great potential in wearable electronic devices. However, due to the high water content, icing and water evaporation problems seriously limit their development. Although additives can ease these disadvantages, the accompanying performance degradation and complex preparation processes couldn't meet application needs. In this work, a convenient method was provided to prepare ionic conductive hydrogels with sensitive electromechanical performance, harsh environmental tolerance, and long-term stability without additives. Based on the hydratability between metal ions and water molecules resulting in spatial condensation of the hydrogel framework, the hydrogel exhibits good flexibility and ionic conductivity (70.3 mS/cm). Furthermore, the metal salt can bind with water molecules to reduce the vapor pressure, thus endowing the hydrogel with good freezing resistance (-40 °C) and long-term stability over a wide temperature range (-20 °C-50 °C). Based on these unique advantages, the hydrogel shows good sensitivity. Even in a harsh environment, it still maintained excellent stability (-20 °C-50 °C, GF = 2.2, R2 > 0.99). Assembled with a Wi-Fi device, the hydrogel sensor demonstrates good health activity and physiological state detection performance, demonstrating great potential for wearable medical devices.

Preparation of sulfated arabinogalactan-loaded hydrogel for wound healing in mouse burn model.

Sulfation of polysaccharides can affect their biological activity by introducing sulfate groups. Skin burns occur regularly and have a great impact on normal survival. In this study, sulfated arabinogalactan (SAG) was prepared by sulfation, and polyvinyl alcohol (PVA) was used to prepare hydrogels for the treatment of scalded skin in mouse. The results show that the main chain of SAG consists of →3-ß-D-Galactose (Gal)-(1, →3, 6)-ß-D-Gal-(1 and →4)-ß-d-Glucose (Glc)-(1. The chain is a neutral polysaccharide composed of T-ß-L-Arabinose (Araf)-(1→, with a molecular weight of 17.9 kDa. At the same time, PVA + SAG hydrogel can promote the scald repair of mouse skin by promoting collagen deposition and angiogenesis, and regulating the TLR4/MyD88/NF-κB signaling pathway. Interestingly, the effect of SAG on promoting the repair of scald wounds is enhanced after AG is derivatized by sulfation. Therefore, the preparation of SAG by sulfation can promote scald repair, and has great application potential in the field of food and medicine.

Fabrication of carboxymethyl tamarind kernel gum-based hydrogel and its applicability in different types of soils for agronomy.

An avant-garde agricultural hydrogel - Carboxymethyl tamarind kernel gum-poly sodium acrylate-polyacrylamide hydrogel was designed by free-radical polymerization of biopolymer: carboxy-methyl tamarind kernel gum and monomers: sodium acrylate, acrylamide, using N,N' methylene bisacrylamide as crosslinker and potassium persulphate as initiator, to explore its application as a soil conditioner. It was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric techniques. Swelling was investigated at different pH and in saline solutions. The fabricated hydrogel absorbed 189 ml/g of distilled water. Minimal 0.1 % hydrogel-amended different soils unveiled an upswing in maximum water holding capacity: Sandy soil (43%), Clay soil (31 %), Silty soil (29 %) & Loamy soil (9 %).; decrease in porosity: Sandy (29 %) > Loamy (15.2 %) > Silty (6 %) > Clay (5.9 %), increase in available water content: Clay soil (17.52 %), Silty (13.45 %), Loamy soil (9.416 %), Sandy soil (10.375 %); increase in bulk density: Clay (1.7 %), Silty (5.3 %), Loamy (10 %) and Sandy (13%) as compared to control sample. These sequels were corroborated by water retention capacity in chickpea plants. The designed hydrogel, as a soil conditioner, was commendable in all types of soils but is worth applying in sandy and loamy soils. This hydrogel richly assists as a soil conditioner and boosts plant performance in a green eco-friendly way.

Stable and antibacterial tannic acid-based covalent polymeric hydrogel for highly selective Pb2+ recovery from lead-acid battery industrial wastewater.

The resource of trace lead (Pb2+) from wastewater bearing intricate components is imperative for sustainable progression of the lead-acid battery industry. Herein, we fabricated a tannic acid-based covalent polymeric hydrogel (TA@PMAM) with antimicrobial properties and stability via facile Michael addition reaction. The incorporation of tannic acid (TA) through robust covalent bond leads to a stable porous 3D covalent polymer network with almost no loss of mechanical properties even after 20 compression cycles. Batch adsorption experiments of TA@PMAM revealed an extraordinary adsorption capacity of Pb2+(Qe =196.6 mg/g), achieving 87.2 % of Pb2+ adsorption within the first 5 min owing to porous structure, numerous adsorption sites and good hydrophilicity. Moreover, TA@PMAM demonstrated a strong affinity for Pb2+ in the presence of the interfere metal ions (Cu2+, Co2+, Mn2+etc.) due to the carbonyl and phenolic hydroxyl that can specifically pair with Pb2+. Stable adsorption properties of TA@PMAM were confirmed in fixed bed column adsorption experiment using lead-acid batteries wastewater, retaining 79.56 % of initial adsorption capacity even after 10 times' reuse. Besides, TA@PMAM possesses a broad spectrum of antimicrobial properties. This study sheds novel light on the design and fabrication of adsorbent, which holds great potential for commercialization in recovering lead from battery industrial wastewater.

Novel nitrogen-rich hydrogel adsorbent for selective extraction of rare earth elements from wastewater.

Efficient recovery of rare earth elements (REEs) from wastewater is crucial for advancing resource utilization and environmental protection. Herein, a novel nitrogen-rich hydrogel adsorbent (PEI-ALG@KLN) was synthesized by modifying coated kaolinite-alginate composite hydrogels with polyethylenimine through polyelectrolyte interactions and Schiff's base reaction. Various characterizations revealed that the high selective adsorption capacity of Ho (155 mg/g) and Nd (125 mg/g) on PEI-ALG@KLN is due to a combination of REEs (Lewis acids) via coordination interactions with nitrogen-containing functional groups (Lewis bases) and electrostatic interactions; its adsorption capacity remains more than 85 % after five adsorption-desorption cycles. In waste NdFeB magnet hydrometallurgical wastewater, the recovery rate of PEI-ALG@KLN for Nd and Dy can reach more than 93 %, whereas that of Fe is only 5.04 %. Machine learning prediction was used to evaluate adsorbent properties via different predictive models, with the random forest (RF) model showing superior predictive accuracy. The order of significance for adsorption capacity was pH > time > initial concentration > electronegativity > ion radius, as indicated by the RF model feature importance analysis and SHapley Additive exPlanations values. These results confirm that PEI-ALG@KLN has considerable potential in the selective extraction of REEs from wastewater.

Efficient Pb(II) removal from contaminated soils by recyclable, robust lignosulfonate/polyacrylamide double-network hydrogels embedded with Fe2O3 via one-pot synthesis.

Soil heavy metal removal strategies are increasingly valued for effectively reducing contamination and preventing secondary pollution. In this work, a double network hydrogel (Fe2O3@LH), consisting of lignosulfonate (LS) and polyacrylamide with embedded Fe2O3 nanoparticles, was synthesized successfully via a one-pot method and subsequently applied to adsorb lead (Pb) from contaminated soil. Incorporating Fe2O3 into the hydrogel enhances the adsorption capacity of Fe2O3@LH for Pb(II). The Fe2O3@LH hydrogel demonstrates a maximum Pb(II) adsorption capacity of 143.11 mg g-1, with Pb(II) removal mechanisms involving electrostatic adsorption, cation exchange, precipitation reactions, and the formation of coordination complexes, achieving a 22.3 % maximum removal efficiency in soil cultivation experiments. Additionally, the application of Fe2O3@LH markedly reduces the concentrations of cadmium (Cd) and arsenic (As) in the soil, meanwhile enhances the levels of total nitrogen (TN), soil organic matter (SOM), and cation exchange capacity (CEC) by 23.1 %, 10.6 %, and 16.9 %, respectively. Following 90 days of continuous application in the soil, the recovery rate of Fe2O3@LH remains above 75 %. The toxicity assay using zebrafish larvae indicates that Fe2O3@LH demonstrates good biosafety. This study demonstrates the considerable potential of Fe2O3@LH hydrogel for practical application in reducing Pb(II) levels in contaminated soil.

Refining hydrogel-based sorbent design for efficient toxic metal removal using machine learning-Bayesian optimization.

Hydrogel-based sorbents show promise in the removal of toxic metals from water. However, optimizing their performance through conventional trial-and-error methods is both costly and challenging due to the inherent high-dimensional parameter space associated with complex condition combinations. In this study, machine learning (ML) was employed to uncover the relationship between the fabrication condition of hydrogel sorbent and their efficiency in removing toxic metals. The developed XGBoost models demonstrated exceptional accuracy in predicting hydrogel adsorption coefficients (Kd) based on synthesis materials and fabrication conditions. Key factors such as reaction temperature (50-70 °C), time (5-72 h), initiator ((NH4)2S2O8: 2.3-10.3 mol%), and crosslinker (Methylene-Bis-Acrylamide: 1.5-4.3 mol%) significantly influenced Kd. Subsequently, ten hydrogels were fabricated utilizing these optimized feature combinations based on Bayesian optimization, exhibiting superior toxic metal adsorption capabilities that surpassed existing limits (logKd (Cu): increased from 2.70 to 3.06; logKd (Pb): increased from 2.76 to 3.37). Within these determined combinations, the error range (0.025-0.172) between model predictions and experimental validations for logKd (Pb) indicated negligible disparity. Our research outcomes not only offer valuable insights but also provide practical guidance, highlighting the potential for custom-tailored hydrogel designs to combat specific contaminants, courtesy of ML-based Bayesian optimization.

ß-cyclodextrin-modulated ratiometric supramolecular BODIPY fluoroprobe for highly selective and sensitive detection of thiophenol.

Thiophenol (PhSH) is an important industrial intermediate but displays significant toxicity towards environmental and biological systems. Here, we introduce a supramolecular system based on ß-cyclodextrin (ß-CD) and boron dipyrromethene (BODIPY) as a ratiometric fluorescence probe to discriminate PhSH in environmental water samples, cells, and in vivo. In aqueous solutions, BODIPY shows extremely weak fluorescence intensity due to its aggregation into nanometer-sized clusters, which prevents its interaction with thiols. However, within a ß-CD environment, it can selectively and sensitively detect PhSH. Also, the stability of the probe was significantly improved. The mechanism studies based on stoichiometry, NMR spectroscopy, and theoretical calculation revealed distinct intermolecular interactions between ß-CD and BODIPY, including host-guest interactions and hydrogen bonds. Low limit of detection (10.7 nM) and rapid response time (5 min) have been achieved, and the practicality of the supramolecular system (BODIPY@ß-CD) has been verified by actual sample analysis. Furthermore, the first hydrogel-based sensing system for portable PhSH detection has been developed, facilitating rapid and on-site colorimetric visualization across both liquid and gas phases. Most importantly, using a low amount of the probe, early stages of low-dose exposure to PhSH can be visualized in living cells and zebrafish. Therefore, BODIPY@ß-CD is a robust new monitoring tool for the detection of PhSH in various scenarios, indicating the promising application value of the host-guest supramolecular probe in detecting highly toxic substances.

Thermosensitive chitosan-based hydrogel: A vehicle for overcoming the limitations of nose-to-brain cell therapy.

Cell therapy is a promising strategy for treating neurological pathologies but requires invasive methods to bypass the blood-brain barrier restrictions. The nose-to-brain route has been presented as a direct and less invasive alternative to access the brain. The primary limitations of this route are low retention in the olfactory epithelium and poor cell survival in the harsh conditions of the nasal cavity. Thus, using chitosan-based hydrogel as a vehicle is proposed in this work to overcome the limitations of nose-to-brain cell administration. The hydrogel's design was driven to achieve gelification in response to body temperature and a mucosa-interacting chemical structure biocompatible with cells. The hydrogel showed a < 30 min gelation time at 37 °C and >95 % biocompatibility with 2D and 3D cultures of mesenchymal stromal cells. Additionally, the viability, stability, and migration capacity of oligodendrocyte precursor cells (OPCs) within the hydrogel were maintained in vitro for up to 72 h. After the intranasal administration of the OPCs-containing hydrogel, histological analysis showed the presence of viable cells in the nasal cavity for up to 72 h post-administration in healthy athymic mice. These results demonstrate the hydrogel's capacity to increase the residence time in the nasal cavity while providing the cells with a favorable environment for their viability. This study presents for the first time the use of thermosensitive hydrogels in nose-to-brain cell therapy, opening the possibility of increasing the delivery efficiency in future approaches in translational medicine. STATEMENT OF SIGNIFICANCE: This work highlights the potential of biomaterials, specifically hydrogels, in improving the effectiveness of cell therapy administered through the nose. The nose-to-brain route has been suggested as a non-invasive way to directly access the brain. However, delivering stem cells through this route poses a challenge since their viability must be preserved and cells can be swept away by nasal mucus. Earlier attempts at intranasal cell therapy have shown low efficiency, but still hold promise to the future. The hydrogels designed for this study can provide stem cells with a biocompatible environment and adhesion to the nasal atrium, easing the successful migration of viable cells to the brain.