Modulus Of Hydrogels Research Articles

Abstract 305: Bioinspired synthetic hydrogel in pancreatic cancer organoid matrix modeling

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality with a primary hallmark, including dense collagen matrix in the desmoplastic stroma. Organoid technologies often rely on commercially available EHS mouse sarcoma matrix materials, and it remains uncertain how batch-to-batch variability of this matrix impacts the consistency of cancer signaling. Here, we present a novel photo-activated hydrogel tuned to the properties of the desmoplastic stroma in PDAC organoid cultures. Method: We designed multiple synthetic hydrogel materials with tunable mechanical properties, including SP-139 (Stem Pharm, Inc), a polyethylene glycol-based hydrogel functionalized with norbornene and formed with both degradable and non-degradable crosslinking peptides and a cell adhesion peptide (CRGDS). We used rheometry to measure the elastic modulus of the polymerized hydrogel after visible light photoactivation (395 nm) and expanded multiple cancer organoid cultures. RNAseq was performed from patient-derived xenografts to expanded organoids across matrix designs (Cultrex® v. SP-139) and analyzed by GSVA pathway analyses. Result: We optimized the ratio of non-degradable v. degradable crosslinking peptide to support culture expansion and enzymatic digestion with dispase II (125 µg/mL) and collagenase II (1 mg/mL). Using rheometry, SP-139 at 75% v/v had increased elastic modulus versus Cultrex RGF BME matrix Type 2 at 100% v/v (4992±76.3 v. 68.4±5.6 Pa, p<0.0001). Phenotypic growth was confirmed across serial passages (>8) and a diversity of gastrointestinal cancer types (n=5). Baseline growth rates were identical over 48h between SP-139 (75% v/v) and Cultrex (50% v/v) (+13.4% v. +13.0, p=0.75). Growth remained consistent for SP-139 yet increased with Cultrex at interval of 48-96h (+12.9% SP-139 v +22.4% Cultrex, p<0.005) and interval of 96-144h (+13.6% SP-139 v +24.0% Cultrex®, p<0.0001). Therapeutic response was assessed using 3D CellTiter-Glo® using gemcitabine 100 µM (24h) with comparable inhibition of normalized cell viability in SP-139 v. Cultrex® (35.4±1.9% v. 52.3±6.5%, n.s.) and qualitatively with viability staining using calcein AM and Caspase 3/7FITC. RNAseq revealed Cultrex, when compared to SP-139, yielded down regulation of epoxygenase p450 pathways (padj<0.012) and negative regulation of the p38 MAP kinase cascade (padj<0.048). Conclusions: Functionalized PEG-based synthetic hydrogel matrix materials can be tuned for physical properties to mimic cancer tissue microenvironments more accurately. SP-139, designed to mimic the desmoplastic stroma of the pancreatic cancer microenvironment, has favorable properties including controlled growth rates and compatibility with high content imaging by luminescence and fluorescence. RNAseq pathway analysis shows SP-139 maintains pathways of p450 and MAP kinase signaling of importance with therapeutic resistance. Citation Format: Md Shahadat Hossan, Austin Stram, Ethan Samuel Lin, Sean McIlwain, Connie Lebakken, William Richards, Jeremy D. Kratz. Bioinspired synthetic hydrogel in pancreatic cancer organoid matrix modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 305.

Dehydration-Toughing Dual-Solvent Gels with Viscoelastic Transition for Infectious Wound Treatment.

The modulus of traditional biomedical hydrogels increases exponentially meditated by dehydration-stiffing mechanism, which leads to the failure of interface matching between hydrogels and soft tissue wounds. It is found in the study that the dual-solvent gels exhibit dehydration-toughening mechanism with the slowly increasing modulus that are always match the soft tissue wounds. Therefore, dual-solvent glycerol hydrogels (GCFen-gly DGHs) are prepared with hydrophobically modified catechol chitosan (hmCSC) and gelatin based on the supramolecular interactions. GCFen-gly DGHs exhibit excellent water retention capacity with a total solvent content exceeding 80%, permanent skin-like modulus within a range of 0.45 to 4.13kPa, and stable photothermal antibacterial abilities against S, aureus, E. coli, as well as MRSA. Infectious full-thickness rat skin defect model and tissue section analysis indicate that GCFen-gly DGHs are able to accelerate infectious wound healing by alleviating the inflammatory response, promoting granulation tissue growth, re-epithelialization, collagen deposition, and vascular regeneration. As a result, GCFen-gly DGHs is expected to become the next-generation biological gel materials for infectious wound treatment.

Reinforced hydrogel building via formation of alginate-chitosan double network with pH & salt-responsiveness and electric conductivity for soft actuators

Aiming at green and friendly environmental protection, polyvinyl alcohol/sodium alginate/chitosan (PSCS) double network hydrogel was successfully prepared through diffusing the high molecular weight chitosan into PVA/sodium alginate (PS) hydrogel without any other toxic reagents. The polyanion hydrogels could be significantly enhanced by immersing the polyanion hydrogel in high molecular weight chitosan solution without requiring specific structure. The PSCS hydrogel had a compact and rough surface structure with the smaller porosities and larger crystallization degree compared with polyvinyl alcohol/sodium alginate hydrogels and polyvinyl alcohol/sodium alginate/Ca2+ (PSCa) hydrogels. The PSCS hydrogel possessed excellent hydrolysis resistance, the significant pH-sensitive and salt-sensitive swelling. In addition, the flexibility, Young's modulus and mechanical properties of PSCS hydrogel can be adjusted through the changing the content of sodium alginate. Moreover, PS, PSCa and PSCS had electric conductivity, and PSCS showed twice the conductivity compared to PS hydrogel. Based on differences of swelling ratio, a PSCS bilayer hydrogel was designed and showed excellent pH-driven deformation ability. The PSCS hydrogel is expected to expand the application of hydrogels in conditions involving stimulus response, and might serve as a promising intelligent actuators or soft robots.

Antibacterial adhesive based on oxidized tannic acid-chitosan for rapid hemostasis

Currently, bacterial infections and bleeding interfere with wound healing, and multifunctional hydrogels with appropriate blood homeostasis, skin adhesion, and antibacterial activity are desirable. In this study, chitosan-based hydrogels were synthesized using oxidized tannic acid (OTA) and Fe3+ as cross-linkers (CS-OTA-Fe) by forming covalent, non-covalent, and metal coordination bonds between Fe3+ and OTA. Our results demonstrated that CS-OTA-Fe hydrogels showed antibacterial properties against Gram-positive bacteria (Staphylococcus aureus)and Gram-negative bacteria (Escherichia coli), low hemolysis rate (< 2 %), rapid blood clotting ability, in vitro (< 2 min), and in vivo (90 s) in mouse liver bleeding. Additionally, increasing the chitosan concentration from 3 wt% to 4.5 wt% enhanced cross-linking in the network, leading to a significant improvement in the strength (from 106 ± 8 kPa to 168 ± 12 kPa) and compressive modulus (from 50 ± 9 kPa to 102 ± 14 kPa) of hydrogels. Moreover, CS-OTA-Fe hydrogels revealed significant adhesive strength (87 ± 8 kPa) to the cow's skin tissue and cytocompatibility against L929 fibroblasts. Overall, multifunctional CS-OTA-Fe hydrogels with tunable mechanical properties, excellent tissue adhesive, self-healing ability, good cytocompatibility, and fast hemostasis and antibacterial properties could be promising candidates for biomedical applications.

Atomistic insights into the mechanical properties of cross-linked Poly(N-isopropylacrylamide) hydrogel

Poly(N-isopropylacrylamide) (PNIPAM) is a highly versatile thermo-responsive hydrogel with immense potential for applications in biomedicine and tissue engineering. While PNIPAM has been extensively researched, there remains a significant gap in understanding its mechanical behavior at the atomistic scale. To address this challenge, this study employs molecular dynamics (MD) simulations to delve into the mechanical response of cross-linked PNIPAM hydrogels. The uniqueness of this research lies in our emphasis on providing atomic-level insights into the influence of chemical cross-linking and physical entanglements, as well as quantifying their effects during the application of strain. This represents a novel contribution to the study of hydrogels. MD simulations enable us to scrutinize the behavior of individual polymer chains and their intricate interactions in unprecedented detail, shedding light on microscale phenomena that are often inaccessible through experiments alone. To tackle the complexities associated with atomistic simulations of cross-linked hydrogels, we introduce a dynamic cross-linking algorithm. This innovative approach incorporates a nonreactive force field to construct realistic three-dimensional hydrogel microstructures, employing a stepwise bond formation strategy. Our findings underscore the remarkable impact of increasing the Degree of Cross-linking (DoC) and/or the Degree of Polymerization (DoP) on enhancing the robustness and elastic modulus of PNIPAM hydrogels. Additionally, we uncover the stochastic nature of chemical cross-linking, leading to the formation of anisotropic super-fragments when DoC exceeds a critical threshold. Furthermore, this research highlights the pivotal role of low strain rates on the order of 106 s−1 in accurately modeling the mechanical properties of hydrogels using MD simulations. This approach enables us to obtain meaningful quantitative mechanical properties that align with experimental results reported in the existing literature. In summary, this paper offers an unprecedented level of insight into the intricate interplay of chemical cross-linking and physical entanglements, providing a foundation for future research in this domain.

Hybridized cellulose nanocrystals enhanced the temperature resistance and viscoelasticity of the fracturing fluid network

This study aimed to fabricate a novel, low-cost, and environmental-friendly cellulose composite hydrogels based on cellulose nanocrystals (CNCs) and carboxymethyl cellulose (CMC-Na) via hybridizing methods. The performance of composite hydrogels was characterized and the nanocrystals enhancing hydrogels performance mechanism was analyzed, which showed that the apparent viscosity, temperature tolerance, elastic modulus, and tensile strength of cellulose hydrogels were improved by CNCs. Compared with the cellulose hydrogels, the viscosity of the cellulose composite hydrogels at 120 °C reached 195 mPa·s, with an increase of 200 %, and the elastic modulus was 30 Pa, with an increase of about 253 %. Furthermore, the microscopic analysis revealed that CNCs can play the role of nucleus and skeleton in the network structure of cellulose composite hydrogels and obviously enhanced the strength of the network structure. It is obvious to improve the performance of cellulose hydrogels by adding CNCs into the cellulose composite hydrogels. This method provides a new idea for the development of fracturing fluids suitable for unconventional reservoirs.

Regulation of Cell Adhesion on Physically Crosslinked Hydrogels Composed of Amino Acid‐Based Polymers by Changing Elastic Modulus Using Shape Fix/Memory Properties

AbstractThe elastic modulus of hydrogels is one of the most important factors for controlling cell fate. In this study, hydrogels composed of poly(N‐acryloylglycinamide) (PNAGAm) grafted with arginine (R)–glycine (G)–aspartic acid (D)–serine (S) peptide is designed without a chemical crosslinker. The hydrogels are prepared by the conventional radical copolymerization of N‐acryloylglycinamide with a polymerizable RGDS peptide. The peptide grafting ratio is easily controlled by adjusting the feed composition for polymerization. The hydrogels exhibit thermo‐responsiveness of the upper critical solution temperature type based on the PNAGAm moiety. This characteristic reflects the shape fix/memory properties of hydrogels because of the reversible formation of multiple hydrogen bonds. The cell adhesiveness of the hydrogels drastically improves in the presence of a small amount of the peptide graft. The hydrogels exhibit good biocompatibility; the adhered cells proliferate on the hydrogels, and macrophages do not show activation or inflammation. Surfaces with different elastic modulus regions are successfully constructed on the same hydrogel by using shape fix/memory properties, allowing the regulation of cell adhesion. This hydrogel system offers promising opportunities for the design and application of functional cell scaffolds.

Injectable Peptide Hydrogels Loaded with Murine Embryonic Stem Cells Relieve Ischemia In Vivo after Myocardial Infarction.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide, especially in aging and metabolically unhealthy populations. A major target of regenerative tissue engineering is the restoration of viable cardiomyocytes to preserve cardiac function and circumvent the progression to heart failure post-MI. Amelioration of ischemia is a crucial component of such restorative strategies. Angiogenic β-sheet peptides can self-assemble into thixotropic nanofibrous hydrogels. These syringe aspiratable cytocompatible gels were loaded with stem cells and showed excellent cytocompatibility and minimal impact on the storage and loss moduli of hydrogels. Gels with and without cells were delivered into the myocardium of a mouse MI model (LAD ligation). Cardiac function and tissue remodeling were evaluated up to 4 weeks in vivo. Injectable peptide hydrogels synergized with loaded murine embryonic stem cells to demonstrate enhanced survival after intracardiac delivery during the acute phase post-MI, especially at 7 days. This approach shows promise for post-MI treatment and potentially functional cardiac tissue regeneration and warrants large-scale animal testing prior to clinical translation.

Ovalbumin amyloid-like fibrils/resveratrol self-assembling hydrogel: Preparation, characterization and formation mechanism

Food protein amyloid-like fibrils can significantly increase solution viscosity and promote the formation of entangled gel network due to its high stiffness and extreme aspect ratios. In this study, the ability of hydrophobic resveratrol (RES) deposited on the surface of the ovalbumin (OVA) amyloid-like fibrils (OVAF) to form a new self-assembling hydrogel was explored. The results showed that the simple mixing of RES and OVAF at pH 6.5 can successfully drive the formation of hybrid hydrogels through molecular self-assembly. The interactions between OVAF and RES were confirmed by the results of transmission electron microscope and fluorescence spectra. Non-covalent interactions including hydrophobic interactions and hydrogen bonds played an important role in the formation of the OVAF/RES self-assembling hydrogels. Furthermore, the OVAF/RES hydrogel showed a dense structure, high water holding capacity and remarkable rheological properties. The viscosity and storage modulus of the hybrid hydrogels increased with the increase of the RES and OVAF concentrations. After gastrointestinal digestion, some fibrous structures in the OVAF/RES hydrogels remained, which allowed for continuous release of RES. In summary, the OVAF/RES hybrid hydrogels with tunable structures, encapsulation ability and self-assembly characteristics are expected to be candidates for the delivery of hydrophobic active polyphenols in the food industry.

Effect of polymerization on free water in polyacrylamide hydrogels observed with Brillouin spectroscopy.

Brillouin spectroscopy is used to determine the effects of polymer concentration, crosslinking density, and polymerization on the longitudinal storage and loss moduli of polyacrylamide hydrogels. The model established by Chiarelli et al. is implemented to calculate the speed of sound in the free water [Chiarelli et al., The Journal of the Acoustical Society of America, 2010, 127(3), 1197-1207]. The polymer concentration has the greatest effect on the moduli of the polymer matrix. We determined that the crosslink density has no measurable effect on the logitudinal storage or loss modulus of polyacrylamide hydrogels when measurements are made at GHz frequencies, in contrast to measurements made at kHz frequencies as documented by other studies. However, the moduli are independent of monomer concentration if the acrylamide is not polymerized. We show at the GHz frequency that the incorporation of acrylamide polymer chains affects the mechanical properties of the free water. The speed of sound in the free water is reduced by the introduction of polymerized acrylamide. The long polymer chains and their interactions with the bounded water disrupt the bonding organization of the unbound water, causing a reduction of the average hydrogen bond strength between free water molecules. This results in a decreased speed of sound in the free water and an increase in the longitudinal storage modulus of the hydrogel.

Effect of the shape of hydrogel samples on their stretch‐fracture properties

AbstractHydrogels have broad application prospects, but the measurement of their mechanical properties often lacks stability. This study investigates the mechanical properties of hydrogels, with a specific focus on the influence of sample geometry on the tensile‐fracture testing results. In the process of stretching the hydrogel along its length, increasing the width and thickness will result in uneven stress distribution. When the width of PAM hydrogel is three times that of initial sample (5 mm of width), the elastic modulus, maximum stress, and maximum strain of PAM hydrogel are reduced by about 16.8%, 69.2%, and 26.5%, respectively. Similarly, compared to the initial sample (1 mm of thickness), the elastic modulus of the triple thickness sample was reduced by about 6.5%, the maximum stress was reduced by 31%, and the maximum strain was reduced by 18.3%. In contrast, increasing the length of the hydrogel can improve the tensile properties of the hydrogel. Finite element calculations support these findings that the size increase in the loading direction improves the stress dispersion uniformity. These results indicate that the shape (length, width and thickness) of the hydrogel sample affects the tensile properties of the hydrogel and should be paid attention in related studies.

Porous Polylactide Microparticles as Effective Fillers for Hydrogels.

High-strength composite hydrogels based on collagen or chitosan-genipin were obtained via mixing using highly porous polylactide (PLA) microparticles with diameters of 50-75 µm and porosity values of over 98%. The elastic modulus of hydrogels depended on the filler concentration. The modulus increased from 80 kPa to 400-600 kPa at a concentration of porous particles of 12-15 wt.% and up to 1.8 MPa at a filling of 20-25 wt.% for collagen hydrogels. The elastic modulus of the chitosan-genipin hydrogel increases from 75 kPa to 900 kPa at a fraction of particles of 20 wt.%. These elastic modulus values cover a range of strength properties from connective tissue to cartilage tissue. It is important to note that the increase in strength in this case is accompanied by a decrease in the density of the material, that is, an increase in porosity. PLA particles were loaded with C-phycocyanin and showed an advanced release profile up to 48 h. Thus, composite hydrogels mimic the structure, biomechanics and release of biomolecules in the tissues of a living organism.

Stimuli-Responsive Pressure-Strain Sensor-Based Conductive Hydrogel for Alleviated Non-alcoholic Fatty Liver Disease by Scavenging Reactive Oxygen Species in Adipose Tissue.

A visible light- and reactive oxygen species (ROS)-responsive pressure/strain sensor based on carbon dot (CD)-loaded conductive hydrogel was developed for detecting high-fat diet (HFD) and preventing the risk of non-alcoholic fatty liver disease. The designed nanoparticle consisted of a diselenide polymer dot (dsPD) loaded with a visible light-responsive CD to form dsPD@CD (DSCD). The influence of visible light irradiation and ROS on DSCD facilitated the electron transport, enhancing the conductivity of DSCD-embedded hydrogel (DSCD hydrogel) from 1.3 to 35.9 mS/m. Alternatively, the tensile modulus of the DSCD hydrogel enhanced to 223% after light-induced ROS treatment, which simultaneously impacted the capacitive response (120%). The hydrogel implantation into inguinal white adipose tissue of HFD mice showed 82% higher conductivity and 83% enhanced pressure sensing response to HFD-generated high ROS levels compared with the normal diet-fed mice. Additionally, the ROS scavenging activity of DSCD hydrogel was confirmed by the downregulation of ROS-responsive genes, such as Sod2, Nrf2, and catalase (Cat) in murine primary hepatocytes isolated from fatty liver-induced mice. In addition, in vivo animal studies also confirmed the suppression of hepatic lipogenesis, as shown by decreased Pparγ and Fasn expression and hypertrophy of adipocytes in HFD mice. The distinguishable real-time wireless resistance response observed with pressure sensing indicates the potential application of the device for monitoring the risk of non-alcoholic fatty liver disease. STATEMENT OF SIGNIFICANCE: : A visible-light-induced ROS-responsive carbon dot-loaded conductive hydrogel was developed for the detection of HFD-induced alterations in ROS levels by evaluating the conductivity and electrochemical responses with applied pressure/strain. The implanted hydrogel facilitates the recovery of the inflated adipocytes induced by NAFLD, which reduces fat accumulation in the liver, preventing the risk of NAFLD. Real-time detection based on the resistance response during local compression of the hydrogel is possibly performed utilizing a wireless sensing device, demonstrating the ease of NAFLD monitoring.

Enhanced Mechanical Strength of Metal Ion-Doped MXene-Based Double-Network Hydrogels for Highly Sensitive and Durable Flexible Sensors.

Development of conductive hydrogels with high sensitivity and excellent mechanical properties remains a challenge for constructing flexible sensor devices. Herein, a universal strategy is presented for enhancing the mechanical strength of Mxene-based double-network hydrogels through metal ion coordination effects. Polyacrylamide (PAM)/sodium alginate (SA)/Mxene double-network (PSM-DN) hydrogels were prepared by metal ion impregnation of PAM/SA/Mxene (PSM) hydrogels. High electrical conductivity is achieved due to MXene nanosheets, while the strong coordination bond between metal ions and SA constructs a second network that increases the mechanical strength of the hydrogel by an order of magnitude. Mechanical tests demonstrated that the elastic modulus of hydrogels matches that of human tissues. Hence, they can be used as a highly sensitive electronic skin sensor to recognize the movement of different joints in humans and also as a pressure sensing interface to recognize characters for anticounterfeiting and information transfer. This work can promote the practical application of conductive hydrogels in high-tech fields, such as flexible electronic skin and interface interaction.

A systematic approach to improve printability and cell viability of methylcellulose-based bioinks

Printability in 3D extrusion bioprinting encompasses extrudability, filament formation, and shape fidelity. Rheological properties can predict the shape fidelity of printed hydrogels. In particular, tan(δ), the ratio between loss (G′′) and storage (G′) modulus (G′′/G′), is a powerful indicator of printability. This study explores the effect of different salt, sucrose, and MC concentrations on tan(δ), and therefore the printability of methylcellulose (MC) hydrogels. Salt and sucrose increased G′, lowering tan(δ) and enabling printing of scaffolds with high shape fidelity. Conversely, MC concentration increased G′′ and G′, having a lesser effect on tan(δ). Shape fidelity of three formulations with similar G′ but varying tan(δ) values were compared. Higher tan(δ) led to reduced height, while lower tan(δ) improved shape fidelity. Cell viability increased when reducing MC content, extrusion rate, and nozzle gauge. Higher MC concentration (G′ > 1.5 kPa) increased the influence of needle size and extrusion rate on cell viability. Hydrogels with G′ < 1 kPa could be extruded at high rates with small nozzles, minimally affecting cell viability. This work shows a direct relationship between tan(δ) and printability of MC-based hydrogels. Lowering the complex modulus of hydrogels, mitigates extrusion stress, thus improving cell survival.

Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair.

The application of hydrogels in bone repair is limited due to their low mechanical strength. Simulating bone extracellular matrix, methylacrylylated gelatin (GelMA)/methylacrylylated hyaluronic acid (HAMA)/nano-hydroxyapatite(nHap) composite hydrogels were prepared by combining the double network strategy and composite of nHap in this study. The precursor solutions of the composite hydrogels were injectable due to their shear thinning property. The compressive elastic modulus of the composite hydrogel was significantly enhanced, the fracture strength of the composite hydrogel nearly reached 1 MPa, and the composite hydrogel retained its high water content at above 88%. The composite hydrogels possess good compatibility with BMSCS and have the potential to be used as injectable hydrogels for bone defect treatment.

Carboxymethyl chitosan/polyvinyl alcohol double network hydrogels prepared by freeze-thawing and calcium chloride cross-linking for efficient dye adsorption

The discharge of dye wastewater resulting from rapid industrial development has become a serious environmental concern. Therefore, there is a pressing need to develop efficient methods and technologies for the removal of dye pollutants. This study introduced a double network hydrogel, with varying carboxymethyl chitosan (CMCS) contents and polyvinyl alcohol (PVA), employing a combination of freeze- thawing and calcium chloride cross-linking. The investigation focused on the rheological properties of the hydrogels and their removal ability of acidic blue 93 (AB). The results showed that the strength and viscoelastic modulus of composite hydrogels were positively correlated with the CMCS content, and all composite hydrogels exhibited the typical weak strain overshoot behavior. The pore size of the gel initially decreased and then increased, with the densest pores observed at 4 wt% CMCS, showing the optimal removal ability for AB. The adsorption process followed pseudo second-order kinetic model, dominated by external diffusion, and exhibited inhomogeneous multilayer adsorption. This study unveils the potential of CMCS/PVA gels as adsorbents, offering inspirations for the design and development of polyvinyl alcohol-based gels for applications in the food industry.

Development of Gelatin Methacryloyl/Sodium Alginate Interpenetrating Polymer Network Hydrogels for Bone Regeneration by Activating the Wnt/β-Catenin Signaling Pathway via Lithium Release.

Hydrogels have gained significant attention as biomaterials due to their remarkable properties resembling those of the extracellular matrix (ECM). In the present investigation, we successfully synthesized interpenetrating polymer network (IPN) hydrogels using gelatin methacryloyl (GelMA) and sodium alginate (SA), incorporating various concentrations of lithium chloride (LiCl; 0, 5, and 10 mM), aiming to develop a hydrogel scaffold for bone regeneration. Notably, the compressive modulus of the IPN hydrogels remained largely unaffected upon the inclusion of LiCl. However, the hydrogel with the high concentration of LiCl exhibited reduced fragmentation after compression testing. Intriguingly, we observed a significant improvement in cellular biocompatibility, primarily attributed to activation of the Wnt/β-catenin signaling pathway induced by LiCl. Subsequently, we evaluated the efficacy of the newly developed IPN-Li hydrogels in a rat cranial defect model and found that they substantially enhanced bone regeneration. Nevertheless, it is important to note that the introduction of high concentrations of LiCl did not significantly promote osteogenesis. This outcome can be attributed to the excessive release of Li+ ions into the extracellular matrix, hindering the desired effect. Overall, the IPN-Li hydrogel developed in this study holds great promise as a biodegradable material for bone regeneration applications.

Moduli of Mussel‐Inspired, Metal‐Coordinated Hydrogels Comprising Four‐, Six‐, and Eight‐Arm Polymers

AbstractMetal‐coordinated hydrogels can form a percolated network with transient bonds due to metal ions‐functional group coordination. Each metal ion can link with more than one ligand, leading to intricate speciation of bonding modes. While the mechanics of transient gels made with four‐arm polymers are often studied, less is known about how increasing the number of arms affects the modulus. Using shear rheology, the modulus of hydrogels prepared from four‐, six‐, and eight‐armed poly(ethylene glycols), functionalized with histidine ligands that complex with nickel (II) ions is measured. These gels have matched polymer wt.% and varied pH to compare their moduli. It is considered whether the modulus can be described by established polymer network models by calculating the speciation of metal‐coordinated cross‐links and then incorporating it into a phantom network prediction. This study finds that 1) increasing the number of polymer arms increases the modulus, 2) the phantom network allows reasonable modulus approximation for four‐arm and six‐arm gels, and 3) the modulus of eight‐arm gels exceeds the phantom network prediction. Since polymer cores act as chemical cross‐links and metal‐coordinated cross‐links form network strands, it is possible that increasing the number of metal‐coordinated linkages per molecule reinforces the chemical cross‐link at the polymer core.

Facile preparation and properties of porous poly(vinyl alcohol)/trehalose/nano-clay hydrogels with high mechanical strength for potential application in bone tissue engineering

Among various biomaterials, hydrogels are considered as the most attractive tissue engineering material due to their resemblances to extracellular matrix. However, due to the poor mechanical properties, poly(vinyl alcohol) hydrogels are restricted to be applied in load-bearing tissue repair and regeneration. In this work, we designed a series of porous biocompatible composite hydrogels with tough mechanical properties for bone tissue engineering, consisting of poly(vinyl alcohol), trehalose and nano-clay. These novelty hydrogels were prepared by a facile one-pot method. Compositions, microscopic structures, and mechanical properties of hydrogels were investigated in detail. The maximum compressive strength, compressive modulus, tensile strength, elastic modulus, and toughness of hydrogels attained about 2.71 MPa, 0.163 MPa, 0.741 MPa, 0.084 MPa, and 0.94 MJ/m3, respectively. These as-prepared hydrogels exhibited the excellent mechanical properties, which were ascribed to the hydrogen bond interactions between molecules and nano-enhancement effect of the nano-clay. Meanwhile, as-prepared hydrogels also exhibited a three-dimensional and interconnected porous microstructure, which facilitated the transport of nutrients to promote cells growth. In addition, the mechanical properties and microscopic structures of hydrogels could be controlled by adjusting the concentrations of trehalose and nano-clay. In vitro cell experiments demonstrated that the hydrogels had good biocompatibility. And hydrogels possessed the excellent ability to induce MC3T3-E1 cells osteogenesis to accelerate bone defects repair. Above illustrated results demonstrated that the potential applications of the hydrogels used as bone tissue engineering materials. Therefore, we anticipated this kind of poly(vinyl alcohol)-based composite hydrogel could develop a new strategy for bone tissue repair.