Hydrogel Formation Research Articles

Assessing rheological properties of oxidized Moringa oleifera gum and carboxymethyl chitosan‐based self‐healing hydrogel for additive manufacturing applications

AbstractRheology plays a vital role in pneumatic three‐dimensional (3D) printing of hydrogels. This study investigates the rheological behavior of a novel self‐healing hydrogel (O‐MOG/CMCh) formed by a Schiff base crosslinking reaction between oxidized Moringa oleifera gum (O‐MOG), a biodegradable antimicrobial polysaccharide, and carboxymethyl chitosan (CMCh), a water‐soluble biocompatible chitosan derivative. Three hydrogel formulations were designed using 5% w/v of CMCh with varied concentrations of O‐MOG (3% w/v, 4% w/v, and 5% w/v) and evaluated through rheology analyses, including frequency sweeps, amplitude sweeps, oscillatory thixotropy, and gelation kinetics. These tests revealed that the material has shear thinning, self‐healing properties, a high linear viscoelastic region (LVE), and gel formation times (tgel) of 3.23–4.57 min. The hydrogel synthesized with 5% w/v of O‐MOG composition exhibited the best characteristics for printability based on rheological assessments, and this composition was used for further printing assessment, where bi‐layered 4 × 4 and 2 × 2 grids were successfully printed using 22 G (0.41 mm) and 23 G (0.34 mm) syringes. All the constructs had a printability index value of 1 ± 0.13 and spreading ratios <6.5, demonstrating the feasibility of employing the synthesized hydrogel as an acellular matrix via additive manufacturing.Highlights Self‐healing hydrogel was prepared by mixing the precursors through a cannula. Rheology was examined using standard tests for printability assessment. 3D printability was achieved using two different gauze syringes. Printability parameters were recorded and analyzed for the constructs.

Sustainable varicose vein therapy using functionalized hydrogels derived solely from livestock waste

Developing sustainable and effective treatments for chronic venous insufficiency (CVI) is crucial. In this study, we propose an innovative restorative approach utilizing hydrogels derived from the decellularized extracellular matrix (dECM) of cadaveric vascular tissues, adipose-derived stem cells (ADSCs), and gold nanoparticles (AuNPs). This therapeutic method leverages waste valorization by repurposing discarded cadaveric tissues from slaughterhouse livestock. The dECM hydrogels, enriched with ADSCs and AuNPs, offer a biocompatible scaffold that supports cellular differentiation and vascular integrity. Our approach addresses the limitations of current allo-, auto-, and xenograft methods by enhancing integration and functionality while potentially reducing costs through sustainable practices. This study explores functionalized hydrogel formulation solely generated from agri-food waste, gelation mechanisms, and preliminary cost-effectiveness, presenting a promising new avenue for treating early-stage varicose veins that can ultimately be translated to human models using discarded tissues.

Patterned PVA Hydrogels with 3D Petri Dish® Micro-Molds of Varying Topography for Spheroid Formation of HeLa Cancer Cells: In Vitro Assessment.

Cell spheroids are an important three-dimensional (3D) model for in vitro testing and are gaining interest for their use in clinical applications. More natural 3D cell culture environments that support cell-cell interactions have been created for cancer drug discovery and therapy applications, such as the scaffold-free 3D Petri Dish® technology. This technology uses reusable and autoclavable silicone micro-molds with different topographies, and it conventionally uses gelled agarose for hydrogel formation to preserve the topography of the selected micro-mold. The present study investigated the feasibility of using a patterned Poly(vinyl alcohol) hydrogel using the circular topography 12-81 (9 × 9 wells) micro-mold to form HeLa cancer cell spheroids and compare them with the formed spheroids using agarose hydrogels. PVA hydrogels showed a slightly softer, springier, and stickier texture than agarose hydrogels. After preparation, Fourier transform infrared (FTIR) spectra showed chemical interactions through hydrogen bonding in the PVA and agarose hydrogels. Both types of hydrogels favor the formation of large HeLa spheroids with an average diameter of around 700-800 µm after 72 h. However, the PVA spheroids are more compact than those from agarose, suggesting a potential influence of micro-mold surface chemistry on cell behavior and spheroid formation. This was additionally confirmed by evaluating the spheroid size, morphology, integrity, as well as E-cadherin and Ki67 expression. The results suggest that PVA promotes stronger cell-to-cell interactions in the spheroids. Even the integrity of PVA spheroids was maintained after exposure to the drug cisplatin. In conclusion, the patterned PVA hydrogels were successfully prepared using the 3D Petri Dish® micro-molds, and they could be used as suitable platforms for studying cell-cell interactions in cancer drug therapy.

Fabrication, optimization, and in vitro validation of penicillin-loaded hydrogels for controlled drug delivery

Bacterial infections present a major global challenge. Penicillin, a widely used antibiotic known for its effectiveness and safety, is frequently prescribed. However, its short half-life necessitates multiple high-dose daily administrations, leading to severe side-effects. Therefore, this study aims to address these issues by developing hydrogels which control the release of penicillin and alleviate its adverse effects. Various combinations of aspartic acid and acrylamide were crosslinked by N′, N′-methylene bisacrylamide through a free radical polymerization process to prepare aspartic acid/acrylamide (Asp/Am) hydrogels. The fabricated hydrogels underwent comprehensive characterization to assess physical properties and thermal stability. The soluble and insoluble fractions and porosity of the synthesized matrix were evaluated by sol-gel and porosity studies. Gel fraction was estimated at 88–96%, whereas sol fraction was found 12–4% and porosity found within the 63–78% range for fabricated hydrogel formulations. Maximum swelling and drug release were seen at pH 7.4, demonstrating a controlled drug release from hydrogel networks. The results showed that swelling, porosity, gel fraction, and drug release increased with higher concentrations of aspartic acid and acrylamide. However, integration of N′, N′-methylene bisacrylamide exhibited the opposite effect on swelling and porosity, while increasing gel fraction. All formulations followed the Korsymer–Peppas model of kinetics with ‘r’ values within the range of 0.9740–0.9980. Furthermore, the cytotoxicity study indicated an effective and safe use of hydrogel because the cell viability was higher than 70%. Therefore, these prepared hydrogels show promise candidates for controlled release of Penicillin and are anticipated to be valuable in clinical applications.

From self-Assembly to healing: Engineering ultra-Small peptides into supramolecular hydrogels for controlled drug release

The aim of this study was the evaluation of suitability of novel mucoadhesive hydrogel platforms for the delivery of therapeutics useful for the management of disorders related to the gastrointestinal tract (GI). At this purpose, here we describe the preparation, the physicochemical characterization and drug delivery behaviour of novel hydrogels, based on self-assembling lipopeptides (MPD02-09), obtained by covalently conjugating lauric acid (LA) to SNA’s peptide derivatives gotten by variously combining D- and L- amino acid residues. LA conjugation was aimed at improving the stability of the precursor peptides, obtaining amphiphilic structures, and triggering the hydrogels formation through the self-assembling. Budesonide (BUD), an anti-inflammatory drug, was selected as model because of its use in the treatment in GI disorders. Preliminary studies were performed to correlate the chemical structure of the conjugates with the key physicochemical properties of the materials for drug delivery. Two lipopeptides, MPD03 and MPD08, were found to form hydrogels (MPD03h and MPD08h, respectively) with characteristics suitable for drug delivery. These materials showed mucoadhesiveness of about 60 %. In vitro studies carried out with BUD loaded hydrogels showed about 70 % drug release within 6 h. Wound healing assessed in Caco-2 and HaCaT cells, showed reduction of cell-free area to values lower than 10 %. Taking together these results MPD03h and MPD08h have been shown to be excellent candidates for BUD delivery.

Dry gel spinning of fungal hydrogels for the development of renewable yarns from food waste

BackgroundRenewable materials made using environmentally friendly processes are in high demand as a solution to reduce the pollution created by the fashion industry. In recent years, there has been a growing trend in research on renewable materials focused on bio-based materials derived from fungi.ResultsRecently, fungal cell wall material of a chitosan producing fungus has been wet spun to monofilaments. This paper presents a modification for the fungal monofilament spinning process, by the development of a benign method, dry gel spinning, to produce continuous monofilaments and twisted multifilament yarns, from fungal cell wall, that can be used in textile applications. The fungal biomass of Rhizopus delemar, grown using bread waste as a substrate, was subjected to alkali treatment with a dilute sodium hydroxide solution to isolate alkali-insoluble material (AIM), which mainly consists of the fungal cell wall. The treatment of AIM with dilute lactic acid resulted in hydrogel formation. The morphology of the hydrogels was pH dependent, and they exhibited shear thinning viscoelastic behavior. Dry gel spinning of the fungal hydrogels was first conducted using a simple lab-scale syringe pump to inject the hydrogels through a needle to form a monofilament, which was directly placed on a rotating receiver and left to dry at room temperature. The resulting monofilament was used to make twisted multifilament yarns. The process was then improved by incorporating a heated chamber for the quicker drying of the monofilaments (at 30⁰C). Finally, the spinning process was scaled up using a twin-screw microcompounder instead of the syringe pump. The monofilaments were several meters long and reached a tensile strength of 63 MPa with a % elongation at break of 14. When spinning was performed in the heated chamber, the tensile strength increased to 80 MPa and further increased to 103 MPa when a micro-compounder was used for spinning.ConclusionThe developed dry gel spinning method shows promising results in scalability and demonstrates the potential for renewable material production using fungi. This novel approach produces materials with mechanical properties comparable to those of conventional textile fibers.

Borate bioactive glass enhances 3D bioprinting precision and biocompatibility on a sodium alginate platform via Ca2+ controlled self-solidification

Sodium alginate (SA) has gained widespread acclaim as a carrier medium for three-dimensional (3D) bioprinting of cells and a diverse array of bioactive substances, attributed to its remarkable biocompatibility and affordability. The conventional approach for fabricating alginate-based tissue engineering constructs entails a post-treatment phase employing a calcium ion solution. However, this method proves ineffectual in addressing the predicament of low precision during the 3D printing procedure and is unable to prevent issues such as non-uniform alginate gelation and substantial distortions. In this study, we introduced borate bioactive glass (BBG) into the SA matrix, capitalizing on the calcium ions released from the degradation of BBG to incite the cross-linking reaction within SA, resulting in the formation of BBG-SA hydrogels. Building upon this fundamental concept, it unveiled that BBG-SA hydrogels greatly enhance the precision of SA in extrusion-based 3D printing and significantly reduce volumetric contraction shrinkage post-printing, while also displaying certain adhesive properties and electrical conductivity. Furthermore, in vitro cellular experiments have unequivocally established the excellent biocompatibility of BBG-SA hydrogel and its capacity to actively stimulate osteogenic differentiation. Consequently, BBG-SA hydrogel emerges as a promising platform for 3D bioprinting, laying the foundation for the development of flexible, biocompatible electronic devices.

Concentration modulated microstructure and rheological properties of nanofibrous hydrogels derived from decellularized human amniotic membrane for 3D cell culture

Decellularized amnion (dAM)-derived hydrogels have been extensively exploited for versatile medical and therapeutical applications, particularly for soft tissue engineering of skin, vascular graft, and endometrium. In contrast to polyacrylamide-based hydrogels, which have been extensively employed as a 3D cell culture platform, the cell response of dAM hydrogel is yet to be understood. In this study, we have prepared hydrogels containing different concentrations of dAM and systematically investigated their microstructural features, gelation kinetics, and rheological properties. The results show that dAM hydrogels possess a network of fibers with an average diameter of 56 ± 5 nm at 1% dAM, which increases to 110 ± 14 nm at 3% dAM. The enhanced intermolecular crosslinking between the microfibrillar units increases the gelation rate in the growth phase of the self-assembly process. Moreover, increasing the concentration of dAM in the hydrogel formulation (from 1 to 3%w/v) enhances the dynamic mechanical moduli of the derived hydrogels by about two orders of magnitude (from 41.8 ± 2.5 to 896.2 ± 72.3 Pa). It is shown that the variation in the hydrogel stiffness significantly affects the morphology of dermal fibroblast cells cultured in the hydrogels. It is shown that the hydrogels containing up to 2%w/v dAM provide a suitable microenvironment for embedded fibroblast cells with spindle-like morphology. Nevertheless, at the higher concentration, an adverse effect on the proliferation and morphology of fibroblast cells is noticed due to stiffness-induced phenotype transformation of cells. Concentration-modulated properties of dAM hydrogels offer an in vitro platform to study cell-related responses, disease modeling, and drug studies.Graphical abstract

Preparation, structural characterization, and functional properties of wheat gluten amyloid fibrils-chitosan double network hydrogel as delivery carriers for ferulic acid

It has been demonstrated that ferulic acid (FA) can be effectively encapsulated using wheat gluten amyloid fibrils (AF) and chitosan (CS) in a double network hydrogel (DN) form, with cross-linking mediated by Genipin (GP). Within this system, the DN comprising gluten AF-FA and CS-FA exhibited optimal loading metrics at a formulation designated as DN8, achieving a load efficiency of 88.5 % and a load capacity of 0.78 %. Analysis through fluorescence quenching confirmed that DN8 harbored the highest quantity of FA. Fourier-transform infrared spectroscopy (FTIR) further verified a significant increase in β-sheet content post-hydrogel formation, enhancing the binding capacity for FA. Rheological assessments indicated a transition from solution to gel, delineating the phase state of the DN. Comprehensive in vitro digestion studies revealed that DN8 provided superior sustained release properties, exhibited the highest total antioxidant capacity, and displayed potent inhibitory activities against angiotensin I converting enzyme (ACE) and acetylcholinesterase (Ach-E). Additionally, the DN significantly bolstered the stability of FA against photothermal degradation. Collectively, these findings lay foundational insights for the advancement of the wheat gluten AF-based delivery system for bioactive compounds and provided a theoretical basis for the development of functional foods.

Contemporary directions in the therapy of sensory hearing loss

<b>Introduction:</b> More than 5% of the world’s population experience hearing impairment. The most common form is presbycusis (age-related hearing loss; ARHL). It affects almost one in three people over the age of 65. The hair cells of the cochlea play an important role in the process of sound registration. Genetic mutations, aging and environmental factors can cause damage that contributes to the hearing loss.<b>Methods and results:</b> The currently explored research directions include drug treatments, gene therapies, and stem cell therapies. To date, no significant differences in the therapeutic effect depending on the route of corticosteroid administration have been demonstrated in patients with moderate to severe hearing loss. New dexamethasone-containing hydrogel formulations, as well as lipid formulations, thermosensitive polymers, and nanoparticles, have been developed to achieve high drug concentrations in the inner ear structures. Otoprotective effects of antioxidants or substances that modify the toxic effects of e.g. cisplatin, are also being studied. Attempts at auditory cells’ regeneration seem promising in hearing loss research. Substances that regulate the central mechanisms of the Notch and Wnt pathways are being explored to this end. The genetic determinants of presbycusis suggest that interference at the level of specific genes may be a promising option for the treatment of this condition. With the CRISPR/Cas9 technology, the functions of inner ear genes can be effectively studied by disrupting normal gene alleles. The CRISPR/Cas9 complexes developed to target specific genes are delivered using cationic lipids, proteins, and viral vectors. They are then transported through the round window membrane by diffusion, without the need to surgically disrupt the inner ear. The potential of using antisense oligonucleotides to treat hereditary deafness caused by hair cell degeneration has also been established. Another research direction is related to stem cells being used for the development of in vitro 3D models of the human inner ear. Studies are also pursued to identify the mechanisms underlying the formation of cochlear organoids from pluripotent cells as well as determine the critical time points and events for cochlear sensory epithelial development and targeted hair cell differentiation.<b>Conclusions:</b> In summary, significant progress has been made over the past decade in the search for novel therapies for sensory hearing loss. This line of research remains an ambitious and important area for further exploration.

Visible light photo-crosslinking of biomimetic gelatin-hyaluronic acid hydrogels for adipose tissue engineering

Tissue engineering (TE) of adipose tissue (AT) is a promising strategy that can provide 3D constructs to be used for in vitro modelling, overcoming the limitations of 2D cell cultures by closely replicating the complex breast tissue extracellular matrix (ECM), cell-cell, and cell-ECM interactions. However, the challenge in developing 3D constructs of AT resides in designing artificial matrices that can mimic the structural properties of native AT and support adipocytes biological functions. Herein, we developed photocrosslinkable hydrogels by employing gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) to mimic the collagenous and glycosaminoglycan components of AT microenvironment, respectively. The physico-mechanical properties of the hydrogels were tuned to target AT biomimetic properties by varying the hydrogel formulation (with or without hyaluronic acid), and the amount of photoinitiator (ruthenium/sodium persulfate) used to crosslink the hydrogels via visible light. The physical and mechanical properties of the developed hydrogels were tuned by varying the material formulation and the photoinitiator concentration. Preadipocytes were encapsulated inside the hydrogels and differentiated into mature adipocytes. Findings enlightened that HAMA addition in hybrid hydrogels boosted an increased lipid accumulation. The engineered biomimetic adipocyte-based constructs resulted promising as scaffolds or 3D in vitro models of AT.

Influence of steel slag content on the mechanical and hydraulic properties of compacted silt-bentonite mixtures

ABSTRACT The reuse of by-products has become increasingly important as a means of minimising the consumption of natural resources and reducing waste disposal. This study examines the potential reuse of steel slag for soil stabilisation, with benefits such as conserving natural resources and mitigating the greenhouse gas emissions associated with the production of conventional stabilising agents. It focuses on evaluating the effect of pozzolanic reactions on the strength and stiffness of both loess silt and silt-bentonite mixtures. The experimental tests included the physical characterisation of granular materials, reactivity tests of the pozzolanicity of soil mixtures, compaction tests, unconfined compression tests, and hydraulic conductivity tests. The impact of the curing period was also analysed to quantify the effects of natural cementation and the development of hydrogels within soil pores on the compacted soil properties. The findings suggest that adding steel slag can significantly increase the strength and the stiffness of compacted loess silts by over 300% and 500%, respectively, after 56 days of curing, substantially reducing the hydraulic conductivity of granular materials, such as the tested silt, as hydrogels partially occupy the pores available for liquid flow. It should be noted that the chemical reactions during hydrogel formation may hinder the free expansion of clay mixtures and release Ca2+ ions, thereby counteracting the expected reduction in hydraulic conductivity when bentonite is added to compacted earthen barriers.

Design of High-Performance Molecular Imprinted Magnetic Nanoparticles-Loaded Hydrogels for Adsorption and Photodegradation of Antibiotics from Wastewater.

A hydrogel formulation of 2-hydroxy ethyl methacrylate (HEMA) containing covalently linked magnetite nanoparticles was developed to actively facilitate the selective removal and photocatalytic degradation of antibiotics. To this purpose, the hybrid materials were molecularly imprinted with Lomefloxacin (Lome) or Ciprofloxacin (Cipro), achieving a selectivity of 60% and 45%, respectively, starting from a solution of XX concentration. After the adsorption, the embedded magnetite was used with the double function of (i) magnetically removing the material from water and (ii) triggering photo-Fenton (PF) reactions assisted by UVA light and H2O2 to oxidize the captured antibiotic. The success of the material design was confirmed by a comprehensive characterization of the system from chemical-physical and morphological perspectives. Adsorption and degradation tests demonstrated the material's ability to efficiently degrade Lome until its complete disappearance from the electrospray ionization (ESI) mass spectra. Regeneration tests showed the possibility of reusing the material for up to three cycles. Ecotoxicological tests using algae Rapidocelis subcapitata, crustaceans Daphnia magna, and bacteria Vibrio fischeri were performed to evaluate the ecosafety of our synthesized materials.

Bioactive Hydrogel Formulation Based on Ferulic Acid-Grafted Nano-Chitosan and Bacterial Nanocellulose Enriched with Selenium Nanoparticles from Kombucha Fermentation.

Selenium nanoparticles (SeNPs) have specific properties that result from their biosynthesis particularities. Chitosan can prevent pathogenic biofilm development. A wide palette of bacterial nanocellulose (BNC) biological and physical-chemical properties are known. The aim of this study was to develop a hydrogel formulation (SeBNCSFa) based on ferulic acid-grafted chitosan and bacterial nanocellulose (BNC) enriched with SeNPs from Kombucha fermentation (SeNPsK), which could be used as an adjuvant for oral implant integration and other applications. The grafted chitosan and SeBNCSFa were characterized by biochemical and physical-chemical methods. The cell viability and proliferation of HGF-1 gingival fibroblasts were investigated, as well as their in vitro antioxidant activity. The inflammatory response was determined by enzyme-linked immunosorbent assay (ELISA) of the proinflammatory mediators (IL-6, TNF-α, and IL-1β) in cell culture medium. Likewise, the amount of nitric oxide released was measured by the Griess reaction. The antimicrobial activity was also investigated. The grafting degree with ferulic acid was approximately 1.780 ± 0.07% of the total chitosan monomeric units, assuming single-site grafting per monomer. Fourier-transform infrared spectroscopy evidenced a convolution of BNC and grafted chitosan spectra, and X-ray diffraction analysis highlighted an amorphous rearrangement of the diffraction patterns, suggesting multiple interactions. The hydrogel showed a high degree of cytocompatibility, and enhanced antioxidant, anti-inflammatory, and antimicrobial potentials.

A bioactive xyloglucan polysaccharide hydrogel mechanically enhanced by Pluronic F127 micelles for promoting chronic wound healing

Chronic wounds represent a formidable global healthcare challenge due to the bacteria infections and uncontrollable inflammation responses, while developing wound healing materials capable of resolving these issues remains a challenge. In this study, we integrated xyloglucan (XG) with Pluronic F127 diacrylate (F127DA)to develop a composite hydrogel for wound healing, where the XG introduced anti-inflammation and anti-bacterial properties to the construct, and F127DA provides the photocurable properties essential for hydrogel formation and robust mechanical characteristics to achieve physical strength that matches tissue regeneration. The material characterizations suggested that XG/F127DA hydrogels had great biostability, blood compatibility and antibacterial effects, which was suitable to be used as a wound healing material. The in vitro analysis by culturing L929 fibroblasts on the hydrogel surface demonstrated that the inclusion of XG could promote the cellular proliferation rate, migration rate, and re-epithelialization-related marker expression, while downregulate the inflammation process. The XG/F127DA hydrogel was further used for the full-thickness skin wound healing test on mice, where the inclusion of XG significantly increased the wound closure rate through reducing the inflammation responses, and promote re-epithelialization and angiogenesis. These results indicated that XG/F127DA hydrogel has great potential to be used for wound healing in future clinical translation.

Eco-Friendly g-C3N4/Carboxymethyl Cellulose/Alginate Composite Hydrogels for Simultaneous Photocatalytic Degradation of Organic Dye Pollutants.

The presented study was focused on the simple, eco-friendly synthesis of composite hydrogels of crosslinked carboxymethyl cellulose (CMC)/alginate (SA) with encapsulated g-C3N4 nanoparticles. The structural, textural, morphological, optical, and mechanical properties were determined using different methods. The encapsulation of g-C3N4 into CMC/SA copolymer resulted in the formation of composite hydrogels with a coherent structure, enhanced porosity, excellent photostability, and good adhesion. The ability of composite hydrogels to eliminate structurally different dyes with the same or opposite charge properties (cationic Methylene Blue and anionic Orange G and Remazol Brilliant Blue R) in both single- and binary-dye systems was examined through adsorption and photocatalytic reactions. The interactions between the dyes and g-C3N4 and the negatively charged CMC/SA copolymers had a notable influence on both the adsorption capacity and photodegradation efficiency of the prepared composites. Scavenger studies and leaching tests were conducted to gain insights into the primary reactive species and to assess the stability and long-term performance of the g-C3N4/CMC/SA beads. The commendable photocatalytic activity and excellent recyclability, coupled with the elimination of costly catalyst separation requirements, render the g-C3N4/CMC/SA composite hydrogels cost-effective and environmentally friendly materials, and strongly support their selection for tackling environmental pollution issues.

Comprehensive Biosafety Profile of Carbomer-Based Hydrogel Formulations Incorporating Phosphorus Derivatives.

Determining the safety of a newly developed experimental product is a crucial condition for its medical use, especially for clinical trials. In this regard, four hydrogel-type formulations were manufactured, all of which were based on carbomer (Blank-CP940) and encapsulated with caffeine (CAF-CP940), phosphorus derivatives (phenyl phosphinic (CAF-S1-CP940) and 2-carboxyethyl phenyl phosphinic acids (CAF-S2-CP940)). The main aim of this research was to provide a comprehensive outline of the biosafety profile of the above-mentioned hydrogels. The complex in vitro screening (cell viability, cytotoxicity, morphological changes in response to exposure, and changes in nuclei morphology) on two types of healthy skin cell lines (HaCaT-human keratinocytes and JB6 Cl 41-5a-murine epidermal cells) exhibited a good biosafety profile when both cell lines were treated for 24 h with 150 μg/mL of each hydrogel. A comprehensive analysis of the hydrogel's impact on the genetic profile of HaCaT cells sustains the in vitro experiments. The biosafety profile was completed with the in vivo and in ovo assays. The outcome revealed that the developed hydrogels exerted good biocompatibility after topical application on BALB/c nude mice's skin. It also revealed a lack of toxicity after exposure to the hen's chicken embryo. Further investigations are needed, regarding the in vitro and in vivo therapeutic efficacy and safety for long-term use and potential clinical translatability.

Hydrogel-Based Therapies for Ischemic and Hemorrhagic Stroke: A Comprehensive Review.

Stroke remains the second leading cause of death and a major cause of disability worldwide, significantly impacting individuals, families, and healthcare systems. This neurological emergency can be triggered by ischemic events, including small vessel arteriolosclerosis, cardioembolism, and large artery atherothromboembolism, as well as hemorrhagic incidents resulting from macrovascular lesions, venous sinus thrombosis, or vascular malformations, leading to significant neuronal damage. The resultant motor impairment, cognitive dysfunction, and emotional disturbances underscore the urgent need for effective therapeutic interventions. Recent advancements in biomaterials, particularly hydrogels, offer promising new avenues for stroke management. Hydrogels, composed of three-dimensional networks of hydrophilic polymers, are notable for their ability to absorb and retain substantial amounts of water. Commonly used polymers in hydrogel formulations include natural polymers like alginate, chitosan, and collagen, as well as synthetic polymers such as polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polyacrylamide. Their customizable characteristics-such as their porosity, swelling behavior, mechanical strength, and degradation rates-make hydrogels ideal for biomedical applications, including drug delivery, cell delivery, tissue engineering, and the controlled release of therapeutic agents. This review comprehensively explores hydrogel-based approaches to both ischemic and hemorrhagic stroke therapy, elucidating the mechanisms by which hydrogels provide neuroprotection. It covers their application in drug delivery systems, their role in reducing inflammation and secondary injury, and their potential to support neurogenesis and angiogenesis. It also discusses current advancements in hydrogel technology and the significant challenges in translating these innovations from research into clinical practice. Additionally, it emphasizes the limited number of clinical trials utilizing hydrogel therapies for stroke and addresses the associated limitations and constraints, underscoring the need for further research in this field.

3D printing assisted surface patterning process on acrylated hydrogels for contact guidance of fibroblasts

Generating stable and customizable topography on hydrogel surfaces with contact guidance potential is critical as it can direct/influence cell growth. This necessitates the development of new techniques for surface patterning of the hydrogels. We report on the design of a square grid template for surface patterning hydrogels. The template was 3-D printed and has the diameter of a well in a 24-well plate. Hyaluronic acid methacrylate (HA) hydrogel precursor solutions were cast on the 3D printed template's surface, which generated 3D square shape topographies on the HA hydrogel surface upon demolding. The 3D Laser Microscopy has shown the formation of a periodic array of 3D topographies on hydrogel surfaces. 3D Laser and Electron Microscopy Imaging have revealed that this new method has increased the surface area and exposed the underlying pore structure of the HA hydrogels. To demonstrate the method's versatility, we have successfully applied this technique to generate 3D topography on two more acrylate hydrogel formulations, gelatin Methacrylate and polyethylene glycol dimethacrylate. Human neonatal dermal fibroblast cells were used as a model cell line to evaluate the cell guidance potential of patterned HA hydrogel. Confocal fluorescence microscopy imaging has revealed that the 3D surface topographies on HA hydrogels can guide and align the actin filaments of the fibroblasts presumably due to the contact guidance mechanism. The newly developed methodology of 3D topography generation in acrylate hydrogels may influence the cell responses on hydrogel surfaces which can impact biomedical applications such as tissue engineering, wound healing, and disease modeling.

Far-Red Aggregation-Induced Emission Hydrogel-Reinforced Tissue Clearing for 3D Vasculature Imaging of Whole Lung and Whole Tumor.

Understanding the vascular formation and distribution in metastatic lung tumors is a significant challenge due to autofluorescence, antibody/dye diffusion in dense tumor, and fluorophore stability when exposed to solvent-based clearing agents. Here, an approach is presented that redefines 3D vasculature imaging within metastatic tumor, peritumoral lung tissue, and normal lung. Specifically, a far-red aggregation-induced emission nanoparticle with surface amino groups (termed as TSCN nanoparticle, TSCNNP) is designed for in situ formation of hydrogel (TSCNNP@Gel) inside vasculatures to provide structural support and enhance the fluorescence in solvent-based tissue clearing method. Using this TSCNNP@Gel-reinforced tissue clearing imaging approach, the critical challenges are successfully overcome and comprehensive visualization of the whole pulmonary vasculature up to 2µm resolution is enabled, including its detailed examination in metastatic tumors. Importantly, features of tumor-associated vasculature in 3D panoramic views are unveiled, providing the potential to determine tumor stages, predict tumor progression, and facilitate the histopathological diagnosis of various tumor types.