Alginate Hydrogel Research Articles

Differentiation of Human Adipose-derived Stem Cells to Exosome-affected Neural-like Cells Extracted from Human Cerebrospinal Fluid Using Bioprinting Process.

Advancement in tissue engineering has provided novel solutions for creating scaffolds as well as applying induction factors in the differentiation of stem cells. The present research aimed to investigate the differentiation of human adipose-derived mesenchymal stem cells to neural-like cells using the novel bioprinting method, as well as the effect of cerebrospinal fluid exosomes. In the present study, the extent of neuronal proliferation and differentiation of adipose- derived stem cells were explored using the MTT method, immunocytochemistry, and real-- time PCR in the scaffolds created by the bioprinting process. Furthermore, in order to investigate the veracity of the identity of the CSF (Cerebrospinal fluid) derived exosomes, after the isolation of exosomes, dynamic light scattering (DLS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) techniques were used. MTT findings indicated survivability and proliferation of cells in the scaffolds created by the bioprinting process during a 14-day period. The results obtained from real-time PCR showed that the level of MAP2 gene (Microtubule Associated Protein 2) expression increased on days 7 and 14, while the expression of the Nestin gene (intermediate filament protein) significantly decreased compared to the control. The investigation to confirm the identity of exosomes indicated that the CSF-derived exosomes had a spherical shape with a 40-100 nm size. CSF-derived exosomes can contribute to the neuronal differentiation of adipose- derived stem cells in alginate hydrogel scaffolds created by the bioprinting process.

Mg-Sr-Ca containing bioactive glass nanoparticles hydrogel modified mineralized collagen scaffold for bone repair.

The aim of this study is to explore the therapeutic effects of Mg-Sr-Ca containing bioactive glass nanoparticles sodium alginate hydrogel modified mineralized collagen scaffold (Mg-Sr-Ca-BGNs-SA-MC) on the repair of osteoporotic bone defect. During the study, Mg-Sr-Ca containing bioactive glass nanoparticles (Mg-Sr-Ca-BGNs) were synthesized using the sol-gel method, and the Mg-Sr-Ca-BGNs-SA-MC scaffold was synthesized by a simple method. The Mg-Sr-Ca-BGNs and the Mg-Sr-Ca-BGNs-SA-MC scaffold were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The elements of Mg, Sr, Ca and Si were effectively integrated into Mg-Sr-Ca-BGNs. SEM analysis revealed the presence of Mg-Sr-Ca-BGNs on the scaffold's surface. Furthermore, the cytotoxicity of the scaffolds were assessed using a live/dead assay. The result of the live/dead assay demonstrated that the scaffold materials were non-toxic to cell growth. More importantly, the in vivo study indicated that implanted scaffold promoted tissue regeneration and integration with newly formed bone. Overall, the Mg-Sr-Ca-BGNs-SA-MC scaffold is suitable for guided bone regeneration and beneficial to repair of osteoporotic bone defects.

Preparation and characterization of agarose-sodium alginate hydrogel beads for the co-encapsulation of lycopene and resveratrol nanoemulsion

In the study, lycopene and resveratrol nanoemulsion hydrogel beads were prepared by using agarose‑sodium alginate as a carrier and the semi-interpenetrating polymer network technique, characteristics and morphologies were evaluated by scanning electron microscopy, fluorescence microscopy, rheological measurement. The synergistic antioxidant effect of lycopene and resveratrol was confirmed, the best synergistic antioxidant performance is achieved when the ratio of 1:1. To increase the solubility and improve the stability, the lycopene was prepared as solid dispersion added to the nanoemulsion. The encapsulation rate of lycopene and resveratrol reached 93.60 ± 2.94 % and 89.30 ± 1.75 %, respectively, and the cumulative release showed that the addition of agarose slowed down the release rate of the compound, which improves the applicability of lycopene and resveratrol and development of carriers for the delivery of different bioactive ingredients.

Oxidation and adsorption of Sb(III) in wastewater by bifunctional MIL-101(Fe)-Cl loaded sodium alginate hydrogel: Performance and mechanisms

China faces severe antimony pollution due to long-term, high-intensity mining and smelting operations. Long-term exposure to Sb(III) can lead to chronic respiratory problems. Adsorption method is used to remove Sb(III) because of its simplicity, economy and high efficiency. Therefore, a novel MIL-101(Fe)-Cl/SA hydrogel with oxidation-sorption bifunctionality was developed. 1602 cm−1 and 1025 cm−1 correspond to NH and S = O indicate N-chlorosulfonamide is bonded to MIL-101(Fe)-Cl/SA. MIL-101(Fe)-Cl/SA exhibited rough and wrinkled surfaces with numerous irregular particles by SEM. The presence of O (22 %) and Cl (2 %) confirmed the incorporation of N-chlorosulfonamide and SA into MIL-101(Fe)-Cl/SA by EDS and mappings. The adsorption capacities of MIL-101(Fe)-Cl/SA were 86 mg/g at 298 K and 123.21 mg/g at 328 K by Langmuir model. Kinetic and equilibrium correspond to pseudo-second-order and Langmuir model, respectively. Adsorption was spontaneous and endothermic by thermodynamic analysis. MIL-101(Fe)-Cl/SA exhibited enhanced selectivity in solution containing various ions. Moreover, MIL-101(Fe)-Cl/SA demonstrated potential for regeneration and reuse. The removal process primarily involved oxidation, electrostatic interaction, and complexation. In summary, the capability of MIL-101(Fe)-Cl/SA to adsorb and oxidize Sb(III) underscores its promising potential in mitigating the hazards associated with Sb(III).

Tunable Viscoelasticity of Alginate Hydrogels via Serial Autoclaving.

Alginate hydrogels are widely used as biomaterials for cell culture and tissue engineering due to their biocompatibility and tunable mechanical properties. Reducing alginate molecular weight is an effective strategy for modulating hydrogel viscoelasticity and stress relaxation behavior, which can significantly impact cell spreading and fate. However, current methods like gamma irradiation to produce low molecular weight alginates suffer from high cost and limited accessibility. Here, a facile and cost-effective approach to reduce alginate molecular weight in a highly controlled manner using serial autoclaving is presented. Increasing the number of autoclave cycles results in proportional reductions in intrinsic viscosity, hydrodynamic radius, and molecular weight of the polymer while maintaining its chemical composition. Hydrogels fabricated from mixtures of the autoclaved alginates exhibit tunable mechanical properties, with inclusion of lower molecular weight alginate leading to softer gels with faster stress relaxation behaviors. The method is demonstrated by establishing how viscoelastic relaxation affects the spreading of encapsulated fibroblasts and glioblastoma cells. Results establish repetitive autoclaving as an easily accessible technique to generate alginates with a range of molecular weights and to control the viscoelastic properties of alginate hydrogels, and demonstrate utility across applications in mechanobiology, tissue engineering, and regenerative medicine.

Sodium alginate hydrogel encapsulating microglia cell lysate subjected to serum starvation for mitigating glioma cells.

Glioma is the most common malignant tumor in the brain, accounting for over 80% of all primary intracranial tumors. The current clinical treatment has shown certain limitations. Although M1 type microglia can secrete various pro-inflammatory cytokines and are expected to be used for glioma treatment, direct use of microglia may lead to overactivation and trigger immune storms. Therefore, we first found that serum starvation can stimulate the transformation of microglia into M1 type. Subsequently, we found through comparative experiments that the inhibitory effect of microglial cell lysis medium on glioma cells was stronger than that of microglial cell culture medium. Finally, we successfully prepared sodium alginate hydrogel loaded with microglia lysis solution to achieve sustained inhibitory effect on the growth of glioma and avoid its proliferation.

Study the effect of different concentrations of polydopamine as a secure and bioactive crosslinker on dual crosslinking of oxidized alginate and gelatin wound dressings

Alginate hydrogels are commonly used in wound care due to their ability to maintain a moist environment, absorb fluids, and aid wound healing. However, their stability and mechanical properties can sometimes limit their effectiveness. This study explores a new approach by creating a dual network system of oxidized alginate and gelatin hydrogel crosslinked with polydopamine in a single step, with the goal of improving the mechanical properties of these hydrogels. The unique aspect of this research is the comprehensive examination of different polydopamine concentrations in dual crosslinking systems. First, alginate was modified with sodium periodate to create additional active groups on its backbone, and various polydopamine concentrations were then tested to assess their impact on the dual crosslinking network and hydrogel properties. The study involved a range of tests, including FTIR, H-NMR, SEM, gelation time, rheology, adhesion, antioxidant activity, swelling ratio, weight loss, drug release, and cell viability. The addition of polydopamine was found to enhance the crosslinking density (0.859 × 109 mol.cm−3). Additionally, the results indicated improvements in properties such as reduced weight loss, enhanced antioxidant and adhesive qualities, and better mechanical properties (2240 kPa). However, the optimal concentration of polydopamine must be determined to achieve the best properties for a wound dressing. Excessive polydopamine can increase the space between polymer chains, leading to a reduction in crosslinking density and storage modulus. Nevertheless, it can also increase the swelling ratio, degradation rate, pore size, porosity, antioxidant activity, and dopamine release. Therefore, identifying the optimal concentration for a functional hydrogel is crucial. Notably, the hydrogel containing 0.5 mg.mL−1 polydopamine exhibited outstanding cell viability (108 % on the third day), swelling capacity (480 %), storage modulus (2240 kPa), gelation time (3 min), antioxidant activity (42.27 %), and skin adherence (11 kPa), making it an optimal choice for advanced wound management. According to the findings, it is emphasized that the application of this particular hydrogel expedites wound healing, as indicated by wound closure and histological studies. AbbreviationsUnlabelled TableOALoxidized alginateGELgelatinPDApolydopamineEDCsodium meta periodate 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochlorideNHSN-hydroxysuccinimide

Synergistic Etching and Hydrogen Bonding-Induced Self-Assembly of MXene/MOF Hybrid Aerogel for Flexible Room-Temperature Gas Sensing.

Limited by insufficient active sites and restricted mechanical strength, designing reliable and wearable gas sensors with high activity and ductility remains a challenge for detecting hazardous gases. In this work, a thermally induced and solvent-assisted oxyanion etching strategy was implemented for selective pore opening in a rigid microporous Cu-based metal-organic framework (referred to as CuM). A conductive CuM/MXene aerogel was then self-assembled through cooperative hydrogen bonding interactions between the carbonyl oxygen atom in PVP grafted on the surface of defect-rich Cu-BTC and the surface functional hydroxyl group on MXene. A flexible NO2 sensing performance using the CuM/MXene aerogel hybridized sodium alginate hydrogel is finally achieved, demonstrating extraordinary sensitivity (S = 52.47 toward 50 ppm of NO2), good selectivity, and rapid response/recovery time (0.9/4.5 s) at room temperature. Compared with commercial sensors, the relative error is less than 7.7%, thereby exhibiting significant potential for application in monitoring toxic and harmful gases. This work not only provides insights for guiding rational synthesis of ideal structure models from MOF composites but also inspires the development of high-performance flexible gas sensors for potential multiscenario applications.

An injectable fibronectin3-alginate hydrogel driven by dynamic dissolving equilibrium for irregular wound repair

Managing irregular wounds with varying depths presents a challenge due to the limited effectiveness of traditional dressings in promoting wound healing. Injectable hydrogels represent a promising approach for managing irregular wounds with varying depths. However, many existing hydrogels are limited by poor biocompatibility and a lack of active ingredients, which significantly undermines their effectiveness in promoting wound healing. In this study, an injectable alginate hydrogel incorporating Fibronectin3 (FN3) as the active component was developed through the modulation of Ca2+ balance and a gradual physical crosslinking process, enabling administration with a 30 G needle. This gel demonstrates remarkable self-healing properties, capable of withstanding 1500 % strain, and exhibits high biocompatibility. Moreover, blood clotting tests demonstrate a lower clotting index than gauze. Additionally, the cell scratch test shows the positive biological activity of the gel and its potential to enhance the migration of L-929 calls. Experiments on full-thickness wounds in mice significantly confirm that gels containing FN3 can effectively accelerate wound healing. In conclusion, this study presents a simple method utilizing the solvation equilibrium of Ca2+ for creating injectable hydrogels with exceptional wound repair properties, thereby indicating their promise as wound dressings in clinical applications.

The Impact of Gelatin and Fish Collagen on Alginate Hydrogel Properties: A Comparative Study.

Hydrogel materials based on sodium alginate find versatile applications in regenerative medicine and tissue engineering due to their unique properties, such as biocompatibility and biodegradability, and the possibility of the customization of their mechanical properties, such as in terms of the individual requirements of separate clinical applications. These materials, however, have numerous limitations in the area of biological activity. In order to eliminate their limitations, sodium alginate is popularly applied in combination with added gelatin, which represents a product of collagen hydrolysis. Despite numerous beneficial biological properties, matrix materials based on gelatin have poor mechanical properties and are characterized by their ability for rapid degradation in an aqueous environment, particularly at the physiological temperature of the body, which significantly limits the independent application opportunities of this type of composition in the range of scaffolding production dedicated for tissue engineering. Collagen hydrogels, unlike gelatin, are characterized by higher bioactivity, dictated by a greater number of ligands that allow for cell adhesion, as well as better stability under physiological conditions. Fish-derived collagen provides a material that may be efficiently extracted without the risk of mammalian prion infection and can be used in all patients without religious restrictions. Considering the numerous advantages of collagen indicating its superiority over gelatin, within the framework of this study, the compositions of hydrogel materials based on sodium alginate and fish collagen in different concentrations were developed. Prepared hydrogel materials were compared with the properties of a typical composition of alginate with the addition of gelatin. The rheological, mechanical, and physicochemical properties of the developed polymer compositions were evaluated. The first trials of 3D printing by extrusion technique using the analyzed polymer solutions were also conducted. The results obtained indicate that replacing gelatin with fish collagen at an analogous concentration leads to obtaining materials with a lower swelling degree, better mechanical properties, higher stability, limited release kinetics of calcium ions cross-linking the alginate matrix, a slowed process of protein release under physiological conditions, and the possibility of extrusion 3D printing. The conducted analysis highlights that the optimization of the applied concentrations of fish collagen additives to composition based on sodium alginate creates the possibility of designing materials with appropriate mechanical and rheological properties and degradation kinetics adjusted to the requirements of specific applications, leading to the prospective opportunity to produce materials capable of mimicking the properties of relevant soft tissues. Thanks to its excellent bioactivity and lower-than-gelatin viscosity of the polymer solution, fish collagen also provides a prospective solution for applications in the field of 3D bioprinting.

Phage embedded gelatin, alginate and gelatin/alginate-starch based hydrogels for topical bactericidal applications against multi-drug resistant Pseudomonas aeruginosa

Topical phage administration through hydrogels is one of the most efficient ways to inhibit bacterial growth in soft tissues. Hydrogels can benefit the skin by acting as a barrier and also promote tissue regeneration and moisture retention in cases of skin breach. Hydrogels incorporated with bioactive ingredients (BAC) have found their way into skin applications ranging from pharmaceutical to cosmetic products, whereas, phage incorporated hydrogels have been under-explored. In this study, we developed gelatin (protein-based) and alginate (polysaccharide-based) hydrogels (GH & AH) to immobilize phages for topical antibacterial treatments. P. aeruginosa is a common wound infecting pathogen and the strain ATCC 15442 used in this study is a β-lactamase producing multi-drug resistant variant. Gelatin and alginate are natural polymers and were chemically crosslinked (covalent & ionic interactions) to develop matrices that embed phages. Aloe vera extracts were used to synthesize hydrogels to succor the healing process. Starch-incorporated gelatin and alginate gels were also screened for phage immobilization. The addition of starch adversely affected the porosity of the matrices but did not affect the swelling ratio of the hydrogels. SEM analysis revealed porous microstructure of gelatin and alginate hydrogel, where starch addition resulted in cracked surface topography. All the developed hydrogels were amorphous in nature, lacking a regular pattern in the structural orientation of the molecules. Phages were successfully administered into the matrix after hydrogel synthesis through absorption. The swelling ratio of gelatin and alginate hydrogels were 2.6 and 0.5 g/g at 30 min. Phages released in buffer at 30 min were 1.6 x 107 and 2.6 x 106 PFU/mL for gelatin and alginate hydrogels respectively. The antibacterial evaluation of phage-incorporated gels showed a zone of inhibition against phage specific P. aeruginosa in agar plates.

Fabrication of a reusable Ti3C2Tx MXene/ZnO@zinc alginate hydrogel for highly efficient and selective phosphate removal

Nano-Zinc oxide (ZnO) shows great potential for phosphate adsorption, but its tendencies to aggregate and lack of selectivity significantly impact adsorption efficiency. The synthesis of Ti3C2Tx MXene/ZnO complexes efficiently disperses ZnO, thereby enhancing selectivity, while encountering challenges in recovery. In this study, Ti3C2Tx MXene/ZnO-embedded zinc crosslinked alginate hydrogel beads (MXZA) were synthesized by solution-phase and ionic cross-linking methods as a highly efficient, selective, and reusable phosphate adsorbent. MXZA exhibited a maximum adsorption capacity of up to 86.67 mg/g of phosphate, and showed excellent adsorption selectivity in complex solutions (e.g., Cl-, NO3–, and SO42-). In short, the MXZA gel adsorbent has a wide application perspective in the effective and selective removal of phosphate from wastewater.

Engineered CAR-NK Cells with Tolerance to H2O2 and Hypoxia Can Suppress Postoperative Relapse of Triple-Negative Breast Cancers.

Surgical resection is a primary treatment option for patients with triple-negative breast cancer (TNBC), but it is associated with a high rate of postoperative local and metastatic relapse. Although chimeric antigen receptor-engineered NK (CAR-NK) cell therapy can specifically recognize and eradicate tumor cells, its therapeutic potency toward TNBCs is markedly suppressed by the hostile tumor microenvironment, which restricts the infiltration, survival, and effector functions of CAR-NK cells inside tumor masses. In this study, HER1-overexpressing TNBC-targeted CAR-NK (HER1-CAR-NK) cells were genetically engineered with catalase to endow them with tolerance toward the high levels of oxidative stress and hypoxia inside TNBC tumors through the catalytic decomposition of hydrogen peroxide, which is a principle reactive oxygen species inside tumors, into O2. We refer to these cells as HER1-CAR-CAT-NK cells. Upon intratumoral fixation with an injectable alginate hydrogel, HER1-CAR-CAT-NK cells enabled sustained tumor hypoxia attenuation and exhibited markedly enhanced persistence and effector functions inside TNBC tumors. As a result, locoregional HER1-CAR-CAT-NK cell therapy not only inhibited the growth of local primary residual tumors but also elicited systemic antitumor activity to suppress the growth of distant tumors. This study highlights that genetic engineering of HER1-CAR-NK cells with catalase is a promising strategy to suppress the postoperative local and distant relapse of TNBC tumors.

Fabrication and Biomedical Application of Alginate Composite Hydrogels in Bone Tissue Engineering: A Review.

Nowadays, as a result of the frequent occurrence of accidental injuries and traumas such as bone damage, the number of people causing bone injuries or fractures is increasing around the world. The design and fabrication of ideal bone tissue engineering (BTE) materials have become a research hotspot in the scientific community, and thus provide a novel path for the treatment of bone diseases. Among the materials used to construct scaffolds in BTE, including metals, bioceramics, bioglasses, biomacromolecules, synthetic organic polymers, etc., natural biopolymers have more advantages against them because they can interact with cells well, causing natural polymers to be widely studied and applied in the field of BTE. In particular, alginate has the advantages of excellent biocompatibility, good biodegradability, non-immunogenicity, non-toxicity, wide sources, low price, and easy gelation, enabling itself to be widely used as a biomaterial. However, pure alginate hydrogel as a BTE scaffold material still has many shortcomings, such as insufficient mechanical properties, easy disintegration of materials in physiological environments, and lack of cell-specific recognition sites, which severely limits its clinical application in BTE. In order to overcome the defects of single alginate hydrogels, researchers prepared alginate composite hydrogels by adding one or more materials to the alginate matrix in a certain proportion to improve their bioapplicability. For this reason, this review will introduce in detail the methods for constructing alginate composite hydrogels, including alginate/polymer composite hydrogels, alginate/bioprotein or polypeptide composite hydrogels, alginate/bioceramic composite hydrogels, alginate/bioceramic composite hydrogels, and alginate/nanoclay composite hydrogels, as well as their biological application trends in BTE scaffold materials, and look forward to their future research direction. These alginate composite hydrogel scaffolds exhibit both unexceptionable mechanical and biochemical properties, which exhibit their high application value in bone tissue repair and regeneration, thus providing a theoretical basis for the development and sustainable application of alginate-based functional biomedical materials.

Hydrogel encapsulation facilitates a low-concentration cryoprotectant for cryopreservation of mouse testicular tissue

Cryopreserved testicular tissue offers a promising method to restore fertility in male infertility patients. Current protocols rely on high concentrations of penetrating cryoprotectants (pCPAs), such as dimethyl sulfoxide (DMSO), which necessitating complex washing procedures and posing risks of toxicity. Hydrogel encapsulation presents a non-toxic alternative for cellular cryopreservation. This study investigates the effects of various types, concentrations, and thicknesses of hydrogel encapsulation on the cryopreservation of mouse testicular tissue. Testicular tissues loaded with varying concentrations of DMSO were encapsulated in alginate or gelatin-methacryloyl (GelMA) hydrogels. We evaluated hydrogels as potential CPAs to reduce pCPA concentrations and determine optimal combinations for cryopreservation. Post-cryopreservation, tissues were cultured using organ culture methods to assess spermatogenesis progression. Cryomicroscopy and differential scanning calorimetry (DSC) were used to examine ice crystal formation, melting enthalpy, and non-freezing water content in different hydrogels during cooling. Results indicate that 3 % alginate or 5 % GelMA hydrogel with thin encapsulation optimally preserves mouse testicular tissue. Using 20 % DMSO in 5 % GelMA thin encapsulation showed comparable apoptosis rates, improved morphology, higher mitochondrial activity, and enhanced antioxidant capacity compared to conventional 30 % DMSO without encapsulation. This suggests that hydrogel encapsulation reduces pCPA concentration by 10 %, thereby mitigating toxic damage. Hydrogel encapsulation can reduce basement membrane shrinkage of testicular tissue during cryopreservation. Moreover, frozen tissues remained viable with preserved germ cells after being cultured for one week on alginate methacryloyl (AlgMA) hydrogel using the gas-liquid interphase method. Cryomicroscopy and DSC studies confirmed the hydrogel's ability to inhibit ice crystal growth. In conclusion, this study introduces novel strategies for male fertility preservation and advances cryopreservation technology for clinical applications in assisted reproduction.

Hydrogen Production in Microbial Electrolysis Cells Using an Alginate Hydrogel Bioanode Encapsulated with a Filter Bag.

The bacterial anode of microbial electrolysis cells (MECs) is the limiting factor in a high hydrogen evolution reaction (HER). This study focused on improving biofilm attachment to a carbon-cloth anode using an alginate hydrogel. In addition, the modified bioanode was encapsulated by a filter bag that served as a physical barrier, to overcome its low mechanical strength and alginate degradation by certain bacterial species in wastewater. The MEC based on an encapsulated alginate bioanode (alginate bioanode encapsulated by a filter bag) was compared with three controls: an MEC based on a bare bioanode (non-immobilized bioanode), an alginate bioanode, and an encapsulated bioanode (bioanode encapsulated by a filter bag). At the beginning of the operation, the Rct value for the encapsulated alginate bioanode was 240.2 Ω, which decreased over time and dropped to 9.8 Ω after three weeks of operation when the Geobacter medium was used as the carbon source. When the MECs were fed with wastewater, the encapsulated alginate bioanode led to the highest current density of 9.21 ± 0.16 A·m-2 (at 0.4 V), which was 20%, 95%, and 180% higher, compared to the alginate bioanode, bare bioanode, and encapsulated bioanode, respectively. In addition, the encapsulated alginate bioanode led to the highest reduction currents of (4.14 A·m-2) and HER of 0.39 m3·m-3·d-1. The relative bacterial distribution of Geobacter was 79%. The COD removal by all the bioanodes was between 62% and 88%. The findings of this study demonstrate that the MEC based on the encapsulated alginate bioanode exhibited notably higher bio-electroactivity compared to both bare, alginate bioanode, and an encapsulated bioanode. We hypothesize that this improvement in electron transfer rate is attributed to the preservation and the biofilm on the anode material using alginate hydrogel which was inserted into a filter bag.

Fabrication and characterization of prednisolone-loaded chitosan and oxidized sodium alginate hydrogel for drug delivery and its biological applications

Fabrication and characterization of prednisolone-loaded chitosan and oxidized sodium alginate hydrogel for drug delivery and its biological applications

Dual cross-linking mechanism of sodium alginate composite hydrogel for adhesive microneedle patch preparation

The introduction of microneedles has revolutionized transdermal drug delivery. However, solid microneedle patches often fail to conform to the epidermis and adapt to changes in skin curvature, limiting their effectiveness. Using sodium alginate hydrogel to create flexible microneedle patches can address this issue, but conventional sodium alginate hydrogels suffer from inhomogeneous structure, dehydration, and poor mechanical properties. These drawbacks result in reduced drug delivery efficacy and insufficient mechanical robustness. To enhance the performance of sodium alginate hydrogels, this study presents a novel sodium alginate composite hydrogel with a dual cross-linking mechanism. The hydrogel, with a gelatin to sodium alginate ratio of 1:1, exhibited optimal surface morphology and mechanical properties suitable for microneedle patch preparation. The resulting microneedle patch demonstrated excellent water adhesion, securely attaching to skin and oral mucosa surfaces. In vitro experiments confirmed the microneedle's ability to puncture and release the drug, dissolving and releasing the drug within 15 minutes. The patch also showed superior piercing and dissolution properties on the mouth palate, highlighting it may serve as a potential delivery location for more efficient microneedle patch drug administration. In the future, this technology will show great potential in expanding the scope of drug administration for transdermal drug delivery and in reducing the work pressure of healthcare professionals.

Design, infectability, and transcriptomic analysis of transregionally differentiated and scalable lung organoids derived from adult bronchial cells.

The lung is a primary target for many lethal respiratory viruses, leading to significant global mortality. Current organoid models fail to completely mimic the cellular diversity and intricate tubular and branching structures of the human lung. Lung organoids derived from adult primary cells have so far only included cells from the input cell region, proximal or distal. Existing models are expensive. They often require cells from invasive deep lung tissue biopsies. The present study aimed to address these limitations. The lung organoids obtained using an original protocol exhibited transregional differentiation and were derived from relatively more accessible primary cells from the trachea/bronchi. Immortal bronchial cell lines were also used to simplify organoid fabrication and improve its scalability. The lung organoids are formed starting from bronchial cells with fibroblasts feeder cells in an alginate hydrogel coated with base membrane zone proteins. Characterizations were performed using bulk RNA sequencing and tandem mass tags. The resulting organoids express markers of different lung regions and mimic to some extent the tubular and branching morphology of the lung. The proteomic profile of organoid from primary cells and from cell lines was found to evolve towards that of mature lung tissue. Upregulated genes were mostly related to the respiratory system, tube development, and various aspects of respiratory viral infections. Infection with SARS-CoV-2 and influenza H1N1 was successful and did not require organoid disassembly. The organoids matured within 21 days and did not require complex or expensive culture methods. Transregionally differentiated lung organoid may find applications for the study of emerging or re-emerging viral infections and fostering the development of novel in-vitro therapeutic strategies.

3D printing of glycerol-mediated alginate hydrogels with high strength and stiffness

As a biomass material with biodegradability and biocompatibility, sodium alginate (SA) is a good candidate for constructing hydrogels for tissue-mimicking and biomedical scaffold fabricating through extrusion-based 3D printing technology. However, the mechanical strength and stiffness of alginate hydrogels are still not comparable with biological tissues such as tendons and the printability of SA solutions is often poor. Here, a novel strategy for 3D printing of alginate hydrogels with high mechanical performance is developed by using glycerol as a co-solvent for SA solutions. The addition of glycerol (GL) enables the formation of a homogenous SA/GL solution with a high solid content of 12–20 wt.% and endows crosslinked SA hydrogels with high stretchability. By applying uniaxial stretches, hydrogel filaments prepared with concentrated SA/GL solutions reveal a high tensile strength of 36.6–161.3 MPa, Young's modulus of 59.2–1964.2 MPa, and elongation at break of 8.5 %–106.2 % due to the high orientated and closely packed SA chains. SA/GL solutions become more solid-like with increasing SA concentration, and the solution with a solid content of 16 wt.% exhibits optimal 3D printability because of the appropriate rheological properties and thixotropic behavior. By designing the deforming-and-fixing process, 3D printed high-strength alginate hydrogels with complex structures are prepared, broadening the application of alginate hydrogels in load-bearing and biomedical fields.