Mechanical Properties Of Hydrogels Research Articles

Integrating Mechanics and Bioactivity: A Detailed Assessment of Elasticity and Viscoelasticity at Different Scales in 2D Biofunctionalized PEGDA Hydrogels for Targeted Bone Regeneration.

Methods for promoting and controlling the differentiation of human mesenchymal stem cells (hMSCs) in vitro before in vivo transplantation are crucial for the advancement of tissue engineering and regenerative medicine. In this study, we developed poly(ethylene glycol) diacrylate (PEGDA) hydrogels with tunable mechanical properties, including elasticity and viscoelasticity, coupled with bioactivity achieved through the immobilization of a mixture of RGD and a mimetic peptide of the BMP-2 protein. Despite the key relevance of hydrogel mechanical properties for cell culture, a standard for its characterization has not been proposed, and comparisons between studies are challenging due to the different techniques employed. Here, a comprehensive approach was employed to characterize the elasticity and viscoelasticity of these hydrogels, integrating compression testing, rheology, and atomic force microscopy (AFM) microindentation. Distinct mechanical behaviors were observed across different PEGDA compositions, and some consistent trends across multiple techniques were identified. Using a photoactivated cross-linker, we controlled the functionalization density independently of the mechanical properties. X-ray photoelectrin spectroscopy and fluorescence microscopy were employed to evaluate the functionalization density of the materials before the culturing of hMSCs on them. The cells cultured on all functionalized hydrogels expressed an early osteoblast marker (Runx2) after 2 weeks, even in the absence of a differentiation-inducing medium compared to our controls. Additionally, after only 1 week of culture with osteogenic differentiation medium, cells showed accelerated differentiation, with clear morphological differences observed among cells in the different conditions. Notably, cells on stiff but stress-relaxing hydrogels exhibited an overexpression of the osteocyte marker E11. This suggests that the combination of the functionalization procedure with the mechanical properties of the hydrogel provides a potent approach to promoting the osteogenic differentiation of hMSCs.

Quantitative Characterization of RCA-based DNA Hydrogels - Towards Rational Design.

DNA hydrogels hold significant promise for biomedical applications and can be synthesized through enzymatic Rolling Circle Amplification (RCA). Due to the exploratory nature of this emerging field, standardized RCA protocols specifying the impact of reaction parameters are currently lacking. This study varied template sequences and reagent concentrations, evaluating RCA synthesis efficiency and hydrogel mechanical properties through quantitative PCR (qPCR) and indentation measurements, respectively. Primer concentration and stabilizing additives showed minimal impact on RCA efficiency, while changes in polymerase and nucleotide concentrations had a stronger effect. Concentration of the circular template exerted the greatest influence on RCA productivity. An exponential correlation between hydrogel viscosity and DNA amplicon concentration was observed, with nucleobase sequence significantly affecting both amplification efficiency and material properties, particularly through secondary structures. This study suggests that combining high-throughput experimental methods with structural folding prediction offers a viable approach for systematically establishing structure-property relationships, aiding the rational design of DNA hydrogel material systems.

Effectiveness of gellan gum scaffolds loaded with Boswellia serrata extract for in-situ modulation of pro-inflammatory pathways affecting cartilage healing

In this study, we developed a composite hydrogel based on Gellan gum containing Boswellia serrata extract (BSE). BSE was either incorporated directly or loaded into an MgAl-layered double hydroxide (LDH) clay to create a multifunctional cartilage substitute. This composite was designed to provide anti-inflammatory properties while enhancing chondrogenesis. Additionally, LDH was exploited to facilitate the loading of hydrophobic BSE components and to improve the hydrogel's mechanical properties. A calcination process was also adopted on LDH to increase BSE loading. Physicochemical and mechanical characterizations were performed by spectroscopic (XPS and FTIR), thermogravimetric, rheological, compression test, weight loss and morphological (SEM) investigations. RPLC-ESI-FTMS was employed to investigate the boswellic acids release in simulated synovial fluid. The composites were cytocompatible and capable of supporting the mesenchymal stem cells (hMSC) growth in a 3D-conformation. Loading BSE resulted in the modulation of the pro-inflammatory cascade by down-regulating COX2, PGE2 and IL1β. Chondrogenesis studies demonstrated an enhanced differentiation, leading to the up-regulation of COL 2 and ACAN. This effect was attributed to the efficacy of BSE in reducing the inflammation through PGE2 down-regulation and IL10 up-regulation. Proteomics studies confirmed gene expression findings by revealing an anti-inflammatory protein signature during chondrogenesis of the cells cultivated onto loaded specimens. Concluding, BSE-loaded composites hold promise as a tool for the in-situ modulation of the inflammatory cascade while preserving cartilage healing.

Mechanical properties of agarose hydrogels tuned by amphiphilic structures

Agarose is a biocompatible polysaccharide that is capable to form physically cross-linked hydrogels in aqueous dispersion. These materials offer a wide range of applications and are commonly used in the food industry or electrophoresis. Moreover, due to their favourable characteristics (biocompatibility, high water absorption, porosity), agarose hydrogels have recently also found applications also in drug delivery systems, wound dressing, and extracellular matrix (ECM) modelling. This paper presents a comprehensive rheological characterization of agarose hydrogels with various self-assembled amphiphilic structures (CTAB, TTAB, SDS, Tween 20) acting as simple membrane structure models. These findings demostrated that the presence of surfactants of diverse charge above their critical micellar concentration (CMC) can enhance hydrogel mechanical properties. Moreover, pronounced enhancement was observed for cationic surfactant, and even concentrations below CMC resulted in a higher stiffness of the hydrogel. Therefore, both the electrostatic effect and the amphiphilic structure effect can have a significant impact on the rheological properties on agarose hydrogels. These findings are of a significant interest in the field of polymer and surfactants interactions, since agarose is widely considered essentially uncharged. However, it is assumed, that traces of negatively charged groups on the agarose backbone can have a significant impact when interacting with oppositely charged surfactants. Moreover, these findings could be beneficial for better understanding of interaction of polysaccharides (e.g. agarose) and self-assembled amphiphilic structures and can also be considered as a crude model of ECM in which membrane structures are embedded.

Natural Polyelectrolyte Hydrogels with Two Types of Cross-Links with Different Energy

For the first time, gels of a polymer cross-linked by two types of ionic cross-links of different energies, namely trivalent chromium (III) ions and divalent iron (II) ions, were prepared. The negatively charged polysaccharide xanthan, a polyelectrolyte of natural origin, was used as a polymer. A study of xanthan gels cross-linked with each cross-linker separately was carried out to identify the optimal concentrations of each cross-linker for the production of a double cross-linked gel. The mechanical properties of hydrogels under oscillatory shear deformations were then studied. It was demonstrated that the simultaneous use of two cross-linkers resulted in a synergistic increase in the elastic modulus (plateau storage modulus) compared to gels cross-linked with each cross-linker separately. For a gel with two types of cross-links, the elastic modulus was 16 Pa. In contrast, for gels cross-linked with either chromium (III) cations or iron (II) cations, the elastic modulus was approximately 0.6 and 0.5 Pa, respectively. The strong effect can be attributed to the different nature of cross-linking between xanthan macromolecules and chromium (III) and iron (II) cations, as well as the different strength of the cross-links formed. The optimal range of pH values was determined in which a synergistic increase in the elastic modulus of gels with two types of cross-links was observed compared to the corresponding gels cross-linked with each cross-linker separately. Consequently, the concurrent utilisation of two cross-linking agents that generate cross-links with disparate energy levels represents an efficacious strategy to improve the tensile strength of polymer hydrogels.

A multicrosslinked network composite hydrogel scaffold based on DLP photocuring printing for nasal cartilage repair.

Natural hydrogels are widely employed in tissue engineering and have excellent biodegradability and biocompatibility. Unfortunately, the utilization of such hydrogels in the field of three-dimensional (3D) printing nasal cartilage is constrained by their subpar mechanical characteristics. In this study, we provide a multicrosslinked network hybrid ink made of photocurable gelatin, hyaluronic acid, and acrylamide (AM). The ink may be processed into intricate 3D hydrogel structures with good biocompatibility and high stiffness properties using 3D printing technology based on digital light processing (DLP), including intricate shapes resembling noses. By varying the AM content, the mechanical behavior and biocompatibility of the hydrogels can be adjusted. In comparison to the gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA) hydrogel, adding AM considerably enhances the hydrogel's mechanical properties while also enhancing printing quality. Meanwhile, the biocompatibility of the multicrosslinked network hydrogels and the development of cartilage were assessed using neonatal Sprague-Dawley (SD) rat chondrocytes (CChons). Cells sown on the hydrogels considerably multiplied after 7 days of culture and kept up the expression of particular proteins. Together, our findings point to GelMA/HAMA/polyacrylamide (PAM) hydrogel as a potential material for nasal cartilage restoration. The photocuring multicrosslinked network ink composed of appropriate proportions of GelMA/HAMA/PAM is very suitable for DLP 3D printing and will play an important role in the construction of nasal cartilage, ear cartilage, articular cartilage, and other tissues and organs in the future. Notably, previous studies have not explored the application of 3D-printed GelMA/HAMA/PAM hydrogels for nasal cartilage regeneration.

Correlation between synthesis parameters and hyperelasticity of hydrogels: Experimental investigation and theoretical modeling

The mechanical properties of hydrogels are significantly influenced by synthesis parameters. Although the mapping from the space of synthesis parameters to the space of properties has been investigated experimentally, a quantitative theoretical framework is still lacking. In this work, the effect of synthesis parameters on the hyperelastic behaviors of hydrogels was experimentally studied. Subsequently, we conducted theoretical analysis by combining the constitutive model and polymer physics to quantify the correlation between synthesis parameters (the initial water content, current water content, and degree of cross-linking) and hyperelasticity (the elastic modulus, degree of entanglement, and stress-stretch ratio curve) of hydrogels. The internal relation between critical polymer content for entanglement and both the initial water content and degree of cross-linking arises from the scaling laws. By analyzing the critical polymer content for entanglement and comparing it with the current polymer content, hydrogels are categorized as either cross-linking-dominated or entanglement-dominated. The current study indicates that a low degree of cross-linking, i.e., a long-chain structure, is an important prerequisite for plenty of entanglements. Hydrogels with low cross-linking are highly entangled, whether they possess high initial water content/low current water content or low initial water content/high current water content. This work paves the way for the systematic design of synthesis parameters, thereby guiding the modulation and optimization of the overall mechanical properties and the application of hydrogels.

Contactless magnetically responsive injectable hydrogel for aligned tissue regeneration

Cellular alignment plays a pivotal role in several human tissues, including skeletal muscle, spinal cord and tendon. Various techniques have been developed to control cellular alignment using 3D biomaterials. However, the majority of 3D-aligned scaffolds require invasive surgery for implantation. In contrast, injectable hydrogels provide a non-invasive delivery method, gaining considerable attention for the treatment of diverse conditions, including osteochondral lesions, volumetric muscle loss, and traumatic brain injury.We engineered a biomimetic hydrogel with magnetic responsiveness by combining gellan gum, hyaluronic acid, collagen, and magnetic nanoparticles (MNPs). Collagen type I was paired with MNPs to form magnetic collagen bundles (MCollB), allowing the orientation control of these bundles within the hydrogel matrix through the application of a remote low-intensity magnetic field. This resulted in the creation of an anisotropic architecture. The hydrogel mechanical properties were comparable to those of human soft tissues, such as skeletal muscle, and proof of the aligned hydrogel concept was demonstrated.In vitro findings confirmed the absence of toxicity and pro-inflammatory effects. Notably, an increased fibroblast cell proliferation and pro-regenerative activation of macrophages were observed. The in-vivo study further validated the hydrogel biocompatibility and demonstrated the feasibility of injection with rapid in situ gelation. Consequently, this magnetically controlled injectable hydrogel exhibits significant promise as a minimally invasive, rapid gelling and effective treatment for regenerating various aligned human tissues.

Polydopamine-intercalated montmorillonite to mitigate polymerization inhibition for preparation of photothermal antibacterial and hemostatic hydrogel

The mechanical properties of hydrogels with in situ introduced polydopamine (PDA) will always be unsatisfactory owing to the polymerization inhibition of the catechol structure. Therefore, it is necessary to find a way to mitigate the inhibition. In this work, PDA-inserted montmorillonite (MMT) was first prepared. The micro-spacing of the MMT nanolayers limited the oxygen content which prevented the complete oxidation of the dopamine adsorbed between the MMT nanosheet layers and retained the catechol moiety. Then, polydopamine montmorillonite polyacrylamide (PMP) hydrogel was prepared under green LED irradiation. The hydrogel exhibited excellent mechanical properties and adhesive strength, as well as excellent photothermal properties and antimicrobial ability. After irradiation by NIR laser, the PMP hydrogel can be heated up and maintained at 50 ℃ within 2 min, and the antimicrobial rate reached 98 %. Meanwhile, PMP hydrogel presents excellent biocompatibility and hemostatic ability. Therefore, PMP hydrogel has a great potential in the field of photothermal therapy and hemostasis.

Effect of Peptide-Polymer Host-Guest Electrostatic Interactions on Self-Assembling Peptide Hydrogels Structural and Mechanical Properties and Polymer Diffusivity.

Peptide-based supramolecular hydrogels are an attractive class of soft materials for biomedical applications when biocompatibility is a key requirement as they exploit the physical self-assembly of short self-assembling peptides avoiding the need for chemical cross-linking. Based on the knowledge developed through our previous work, we designed two novel peptides, E(FKFE)2 and K(FEFK)2, that form transparent hydrogels at pH 7. We characterized the phase behavior of these peptides and showed the clear link that exists between the charge carried by the peptides and the physical state of the samples. We subsequently demonstrate the cytocompatibility of the hydrogel and its suitability for 3D cell culture using 3T3 fibroblasts and human mesenchymal stem cells. We then loaded the hydrogels with two polymers, poly-l-lysine and dextran. When polymer and peptide fibers carry opposite charges, the size of the elemental fibril formed decreases, while the overall level of fiber aggregation and fiber bundle formation increases. This overall network topology change, and increase in cross-link stability and density, leads to an overall increase in the hydrogel mechanical properties and stability, i.e., resistance to swelling when placed in excess media. Finally, we investigate the diffusion of the polymers out of the hydrogels and show how electrostatic interactions can be used to control the release of large molecules. The work clearly shows how polymers can be used to tailor the properties of peptide hydrogels through guided intermolecular interactions and demonstrates the potential of these new soft hydrogels for use in the biomedical field in particular for delivery or large molecular payloads and cells as well as scaffolds for 3D cell culture.

Rationally designed β-cyclodextrin-crosslinked polyacrylamide hydrogels for cell spheroid formation and 3D tumor model construction

In vitro tumor models are essential for understanding tumor behavior and evaluating tumor biological properties. Hydrogels that can mimic the tumor extracellular matrix have become popular for creating 3D in vitro tumor models. However, designing biocompatible hydrogels with appropriate chemical and physical properties for constructing tumor models is still a challenge. In this study, we synthesized a series of β-cyclodextrin (β-CD)-crosslinked polyacrylamide hydrogels with different β-CD densities and mechanical properties and evaluated their potential for use in 3D in vitro tumor model construction, including cell capture and spheroid formation. By utilizing a combination of β-CD-methacrylate (CD-MA) and a small amount of N,N′-methylene bisacrylamide (BIS) as hydrogel crosslinkers and optimizing the CD-MA/BIS ratio, the hydrogels performed excellently for tumor cell 3D culture and spheroid formation. Notably, when we co-cultured L929 fibroblasts with HeLa tumor cells on the hydrogel surface, co-cultured spheroids were formed, showing that the hydrogel can mimic the complexity of the tumor extracellular matrix. This comprehensive investigation of the relationship between hydrogel mechanical properties and biocompatibility provides important insights for hydrogel-based in vitro tumor modeling and advances our understanding of the mechanisms underlying tumor growth and progression.

Cotton Fabric-Reinforced Hydrogels with Excellent Mechanical and Broad-Spectrum Photothermal Antibacterial Properties.

Antibacterial hydrogel wound dressings hold great potential in eliminating bacteria and accelerating the healing process. However, it remains a challenge to fabricate hydrogel wound dressings that simultaneously exhibit excellent mechanical and photothermal antibacterial properties. Here we report the development of polydopamine-functionalized graphene oxide (rGO@PDA)/calcium alginate (CA)/Polypyrrole (PPy) cotton fabric-reinforced hydrogels (abbreviated as rGO@PDA/CA/PPy FHs) for tackling bacterial infections. The mechanical properties of hydrogels were greatly enhanced by cotton fabric reinforcement and an interpenetrating structure, while excellent broad-spectrum photothermal antibacterial properties based on the photothermal effect were obtained by incorporating PPy and rGO@PDA. Results indicated that rGO@PDA/CA/PPy FHs exhibited superior tensile strength in both the warp (289 ± 62.1 N) and weft directions (142 ± 23.0 N), similarly to cotton fabric. By incorporating PPy and rGO@PDA, the swelling ratio was significantly decreased from 673.5% to 236.6%, while photothermal conversion performance was significantly enhanced with a temperature elevated to 45.0 °C. Due to the synergistic photothermal properties of rGO@PDA and PPy, rGO@PDA/CA/PPy FHs exhibited excellent bacteria-eliminating efficiency for S. aureus (0.57%) and E. coli (3.58%) after exposure to NIR for 20 min. We believe that the design of fabric-reinforced hydrogels could serve as a guideline for developing hydrogel wound dressings with improved mechanical properties and broad-spectrum photothermal antibacterial properties for infected-wound treatment.

Tailoring Network Topology in Mechanically Robust Hydrogels for 3D Printing and Injection.

Tissue engineering and regenerative medicine are confronted with a persistent challenge: the urgent demand for robust, load-bearing, and biocompatible scaffolds that can effectively endure substantial deformation. Given that inadequate mechanical performance is typically rooted in structural deficiencies─specifically, the absence of energy dissipation mechanisms and network uniformity─a crucial step toward solving this problem is generating synthetic approaches that enable exquisite control over network architecture. This work systematically explores structure-property relationships in poly(ethylene glycol)-based hydrogels constructed utilizing thiol-yne chemistry. We systematically vary polymer concentration, constituent molar mass, and cross-linking protocols to understand the impact of architecture on hydrogel mechanical properties. The network architecture was resolved within the molecular model of Rubinstein-Panyukov to obtain the densities of chemical cross-links and entanglements. We employed both nucleophilic and radical pathways, uncovering notable differences in mechanical response, which highlight a remarkable degree of versatility achievable by tuning readily accessible parameters. Our approach yielded hydrogels with good cell viability and remarkably robust tensile and compression profiles. Finally, the hydrogels are shown to be amenable to advanced processing techniques by demonstrating injection- and extrusion-based 3D printing. Tuning the mechanism and network regularity during the cell-compatible formation of hydrogels is an emerging strategy to control the properties and processability of hydrogel biomaterials by making simple and rational design choices.

A Spontaneous In Situ Thiol-Ene Crosslinking Hydrogel with Thermo-Responsive Mechanical Properties.

The thermo-responsive behavior of Poly(N-isopropylacrylamide) makes it an ideal candidate to easily embed cells and allows the polymer mixture to be injected. However, P(NiPAAm) hydrogels possess minor mechanical properties. To increase the mechanical properties, a covalent bond is introduced into the P(NIPAAm) network through a biocompatible thiol-ene click-reaction by mixing two polymer solutions. Co-polymers with variable thiol or acrylate groups to thermo-responsive co-monomer ratios, ranging from 1% to 10%, were synthesized. Precise control of the crosslink density allowed customization of the hydrogel's mechanical properties to match different tissue stiffness levels. Increasing the temperature of the hydrogel above its transition temperature of 31 °C induced the formation of additional physical interactions. These additional interactions both further increased the stiffness of the material and impacted its relaxation behavior. The developed optimized hydrogels reach stiffnesses more than ten times higher compared to the state of the art using similar polymers. Furthermore, when adding cells to the precursor polymer solutions, homogeneous thermo-responsive hydrogels with good cell viability were created upon mixing. In future work, the influence of the mechanical micro-environment on the cell's behavior can be studied in vitro in a continuous manner by changing the incubation temperature.

Bioinspired 3D printed elastomer-hydrogel hybrid with robust interfacial bonding for flexible ionotronics

Hydrogels are widely used in flexible ionotronics due to their continuous conductive phase and good biocompatibility. However, their poor mechanical properties affect their stability and lifespan. It is a significant challenge to prepare hydrogels with both high conductivity and mechanical strength, as improving the mechanical properties often results in a tighter network, which reduces electrical conductivity. Human skin is composed of a stiff collagen fibril scaffold for resisting external damage, and a soft matrix that detect various stimuli through ion transport. Herein, inspired by the structure of human skin, a hydrogel composite with remarkable mechanical properties, high ionic conductivity, and self-healing property is prepared. The composite structure with 3D printed elastomeric skeleton and hydrogel matrix, addresses both the contradiction between the ionic conductivity and mechanical properties of hydrogels, as well as the difficulty of realizing complex macrostructures of the skeleton. The issue of weak interface in composites is resolved by creating interfacial covalent bonds. The composite’s self-healing property, combined with a robust interface, ensure the stability and longevity of the composite when used as flexible sensors. This novel approach of creating robust interface is also employed in the encapsulation of hydrogels and the fabrication of flexible microcircuits.

Preparation and evaluation of chitosan/MCM-41-based spongy hydrogels loaded with tea tree oil

In this study, chitosan, polyvinyl alcohol, gelatin, MCM-41 and tea tree oil (TTO) were used as raw materials. MCM-41-based spongy hydrogels loaded with TTO were synthesized by physical cross-linking method. The TTO was first adsorbed into MCM-41 s. Then different contents of MCM-41 s were added to the hydrogel, which affected the properties of the hydrogel. The structure of hydrogels was analyzed by scanning electron microscopy (SEM) and attenuated total internal reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The mechanical properties of hydrogels were determined by swelling, degradation and ductility evaluation. The antibacterial effect and biocompatibility were determined by in vitro antibacterial and cytotoxicity examinations. In this study, the mechanical property of the hydrogels was enhanced with the increasing content of MCM-41 s. The hydrogels exhibited an excellent antibacterial effect attributed to the synergistic interaction between TTO and chitosan. Furthermore, the hydrogels showed superior biocompatibility property. In conclusion, the hydrogels prepared in this study have great potential for expanding their applications in the bacteriostatic field.

Evaluation of gelatin bloom strength on gelatin methacryloyl hydrogel properties

Gelatin methacryloyl (GelMA) hydrogels are widely used for a variety of tissue engineering applications. The properties of gelatin can affect the mechanical properties of gelatin gels; however, the role of gelatin properties such as bloom strength on GelMA hydrogels has not yet been explored. Bloom strength is a food industry standard for describing the quality of gelatin, where higher bloom strength is associated with higher gelatin molecular weight. Here, we evaluate the role of bloom strength on GelMA hydrogel mechanical properties. We determined that both bloom strength of gelatin and weight percent of GelMA influenced both stiffness and viscoelastic ratio; however, only bloom strength affected diffusivity, permeability, and pore size. With this library of GelMA hydrogels of varying properties, we then encapsulated Swan71 trophoblast spheroids in these hydrogel variants to assess how bloom strength affects trophoblast spheroid morphology. Overall, we observed a decreasing trend of spheroid area and Feret diameter as bloom strength increased. In identifying clear relationships between bloom strength, hydrogel mechanical properties, and trophoblast spheroid morphology, we demonstrate that bloom strength should considered when designing tissue engineered constructs.

Fibrin-Based Hydrogels with Reactive Amphiphilic Copolymers for Mechanical Adjustments Allow for Capillary Formation in 2D and 3D Environments.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improved the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial's suitability for in vitro pre-vascularization of biohybrid implants.

A well plate-based GelMA photo-crosslinking system with tunable hydrogel mechanical properties to regulate the PTH-mediated osteogenic fate

Versatile and efficient regulation of the mechanical properties of the extracellular matrix is crucial not only for understanding the dynamic changes in biological systems, but also for obtaining precise and effective cellular responses in drug testing. In this study, we developed a well plate-based hydrogel photo-crosslinking system to effectively control the mechanical properties of hydrogels and perform high-throughput assays. We improved cell biocompatibility by using gelatin methacryloyl (GelMA) with a visible light photo-crosslinking method. Multiple cell-laden GelMA hydrogels were simultaneously and uniformly created using multi-arrayed 520 nm light-emitting diodes in a well plate format. The elastic modulus of the hydrogels can be widely adjusted (0.5–30 kPa) using a photo-crosslinking system capable of independently controlling the light intensity or exposure time for multiple samples. We demonstrate the feasibility of our system by observing enhanced bone differentiation of human mesenchymal stem cells (hMSCs) cultured on stiffer hydrogels. Additionally, we observed that the osteogenic fate of hMSCs, affected by the different mechanical properties of the gel, was regulated by parathyroid hormone (PTH). Notably, in response to PTH, hMSCs in a high-stiffness microenvironment upregulate osteogenic differentiation while exhibiting increased proliferation in a low-stiffness microenvironment. Overall, the developed system enables the generation of multiple cell-laden three-dimensional cell culture models with diverse mechanical properties and holds significant potential for expansion into drug testing.

The Formulation and Characterization of Wound Dressing Releasing S-Nitrosoglutathione from Polyvinyl Alcohol/Borax Reinforced Carboxymethyl Chitosan Self-Healing Hydrogel.

Self-healing hydrogels often lack mechanical properties, limiting their wound-dressing applications. This study introduced S-Nitrosoglutathione (GSNO) to self-healing hydrogel-based wound dressings. Self-healing hydrogel mechanical properties were improved via polymer blends. Applying this hydrogel to the wound site allows it to self-heal and reattach after mechanical damage. This work evaluated polyvinyl alcohol (PVA)-based self-healing hydrogels with borax as a crosslinking agent and carboxymethyl chitosan as a mechanical property enhancer. Three formulations (F1, F4, and F7) developed self-healing hydrogels. These formulations had borax concentrations of 0.8%, 1.2%, and 1.6%. An FTIR study shows that borate ester crosslinking and hydrogen bonding between polymers generate a self-healing hydrogel. F4 has a highly uniform and regular pore structure, as shown by the scanning electron microscope image. F1 exhibited faster self-healing, taking 13.95 ± 1.45 min compared to other formulations. All preparations had pH values close to neutrality, making them suitable wound dressings. Formula F7 has a high drug content (97.34 ± 1.21%). Good mechanical qualities included high tensile stress-strain intensity and Young's modulus. After 28 h of storage at -20 °C, 5 °C, and 25 °C, the self-healing hydrogel's drug content dropped significantly. The Korsmeyer-Peppas release model showed that the release profile of GSNO followed Fickian diffusion. Thus, varying the concentration of crosslinking agent and adding a polymer affects self-healing hydrogels' physicochemical properties.