Elastic Modulus Of Hydrogels Research Articles

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.

Novel PLCL nanofibrous/keratin hydrogel bilayer wound dressing for skin wound repair

In this study, a novel poly(L-lactate-caprolactone) copolymer (PLCL) nanofibrous/keratin hydrogel bilayer wound dressing loaded with fibroblast growth factor (FGF-2) was prepared by the low-pressure filtration-assisted method. The ability of the keratin hydrogel in the bilayer dressing to mimic the dermis and that of the nanofibrous PLCL to mimic the epidermis were discussed. Keratin hydrogel exhibited good porosity and maximum water absorption of 874.09%. Compared with that of the dressing prepared by the coating method, the interface of the bilayer dressing manufactured by the low-pressure filtration-assisted method (filtration time: 20 min) was tightly bonded, and its bilayer dressing interface could not be easily peeled off. The elastic modulus of hydrogel was about 44 kPa, which was similar to the elastic modulus of the dermis (2–80 kPa). Additionally, PLCL nanofibers had certain toughness and flexibility suitable for simulating the epidermal structures. In vitro studies showed that the bilayer dressing was biocompatible and biodegradable. In vivo studies indicated that PLCL/keratin-FGF-2 bilayer dressing could promote re-epithelialization, collagen deposition, skin appendages (hair follicles) regeneration, microangiogenesis construction, and adipose-derived stem cells (ADSCs) recruitment. The introduction of FGF-2 resulted in a better repair effect. The bilayer dressing also solved the problems of poor interface adhesion of hydrogel/electrospinning nanofibers. This paper also explored the preliminary role and mechanism of bilayer dressing in promoting skin healing, showing that its potential applications as a biomedical wound dressing in the field of skin tissue engineering.

Construction of high-performance polymer hydrogel composite materials for artificial bionic organs

Hydrogel, with excellent hydrophilicity biocompatibility and stimuli responsive, has been widely used in biomedical and artificial organs fields. However, synthetic hydrogel usually displays poor gel strength, poor toughness and slow speed of absorbing water. Therefore, extensive exploratory research is still required to develop new composite materials for the application of bionic viscera. In this work, we constructed a new kind of composite hydrogel by a facile wet chemistry method to cross-link three kinds of polymer resin, polyvinyl alcohol, carboxymethyl cellulose, and carboxymethyl starch. The conductivity, moisture content and elastic modulus of hydrogel can be controlled by the dosage of potassium salt, sodium salt, water and glycerol. After molding and testing, the electrical conductivity, elastic modulus, and moisture content of the artificial liver and kidney organs were similar to those of the corresponding pig viscera, which is superior to most of the current research on hydrogels. This work provides a facile approach to synthesize highly efficient hydrogel, which accelerates the application of hydrogel in bionic organs.

Fabrication and evaluation of chitosan/gelatin/PVA hydrogel incorporating honey for wound healing applications: An in vitro, in vivo study

In this study, physically cross-linked hydrogels were developed by freezing-thawing method while different concentrations of honey were included into the hydrogels for accelerated wound healing. The hydrogel was composed of chitosan, polyvinyl alcohol (PVA), and gelatin with the ratio of 2:1:1 (v/v), respectively. Further, the effect of honey concentrations on antibacterial properties, and cell behavior was investigated. In vivo studies, including wound healing mechanism using rat model and histological analysis of section tissue samples were performed. The results illustrated that the incorporation of honey in hydrogels increased the ultimate strain of hydrogels approximately two times, while reduced the ultimate tensile strength and elastic modulus of hydrogels. Moreover, the antibacterial activities of samples were increased by increasing the concentration of honey. Regarding MTT assay, as the concentration of honey increased, the cell viability of hydrogels was enhanced until an optimal amount of honey. Further, the integration of honey into the hydrogel matrix results in the maintenance of a well-structured layer of epidermis containing mature collagen and accelerates the rate of wound healing. The 3D Chitosan/PVA/Gelatin hydrogel containing honey with appropriate mechanical, antibacterial activity, and biocompatibility could be a promising approach for wound healing.

Thermodynamic analysis and material design to enhance chemo-mechanical coupling in hydrogels for energy harvesting from salinity gradients

Coupling between solution salinity and the mechanics of charged hydrogels presents an opportunity to harvest osmotic energy in a clean and sustainable way. By applying mechanical pressure to retard the swelling or deswelling of hydrogels in saline solutions, the free energy of mixing is converted into mechanical work. This study developed a theoretical framework and experimentally investigated the potential of hydrogels for energy production from salinity gradients. Mathematical modeling revealed the effect of parameters including the charge and elastic modulus of hydrogels, applied pressure, and the solution salinity on energy conversion using different thermodynamic cycles. With proper material design and process control, the thermodynamic efficiency of an ideal process was predicted to exceed 5% with 10 mM and 600 mM NaCl solutions. Experiments with poly (styrene sulfonate) hydrogels verified the theoretically predicted trends and demonstrated more than 10% thermodynamic efficiency for moderate-salinity sources, due to the unique swelling-strengthened mechanical properties of the gels. The study suggests the potential of polyelectrolyte hydrogels in the extraction of energy from low- to moderate-salinity sources and provides a framework for their design.

The effect of water content on the elastic modulus and fracture energy of hydrogel

Both elastic and fracture behavior of hydrogel are affected by its water content. As shown by extensive experimental data, currently prevalent models, which are primarily based on the Flory–Rehner theory (F–R theory), are unable to correctly capture the effect of water content (or conversely polymer fraction) on the elastic modulus of hydrogels. Lake–Thomas theory cannot provide correct predictions on fracture toughness with different water content conditions as well. In this work, we carry out experiments on polyacrylamide (PAAm) gel and discover scaling-laws that differ significantly in the swollen and dehydrated state in addition to contradicting F–R model. We also derive scaling laws that are consistent with our experiments. Intriguingly, we find that the application of the scaling theory to fracture problems of the hydrogel can also provide a better theoretical prediction. An intriguing implication of this result is that the study of the fracture threshold of soft matter may be replaced to some extent by merely the studying of their elastic modulus.

Evaluating the effect of pH on mechanical strength and cell compatibility of nanostructured collagen hydrogel by the plastic compression method

Objective(s): One of the main constraints of collagen hydrogel scaffolds for using in tissue engineering is mechanical weakness. Plastic compression (PC) is a physical method to overcome the mechanical limitation of collagen hydrogel. Materials and Methods: In this study, the effects of pH on mechanical and biological properties of PC hydrogels were investigated. Collagen hydrogels were fabricated at neutral (pH=7.4) and alkaline pH (pH=8.5), and then underwent plastic compression to prepare final hydrogels. The stability, mechanical properties, morphology and cell compatibility of hydrogels were investigated. Results: The results illustrated that increasing in polymerization pH was associated with improvement in both tensile strength and elastic modulus of hydrogels. Furthermore, cell viability assay confirmed cell survival in both hydrogels prepared at alkaline and neutral pH. Conclusion: The results suggest that a slightly basic pH during hydrogel production is an appropriate approach to construct PC collagen hydrogels with an enhanced stability and mechanical properties as well as better handling before PC process.

Standardized Nanomechanical Atomic Force Microscopy Procedure (SNAP) for Measuring Soft and Biological Samples

We present a procedure that allows a reliable determination of the elastic (Young’s) modulus of soft samples, including living cells, by atomic force microscopy (AFM). The standardized nanomechanical AFM procedure (SNAP) ensures the precise adjustment of the AFM optical lever system, a prerequisite for all kinds of force spectroscopy methods, to obtain reliable values independent of the instrument, laboratory and operator. Measurements of soft hydrogel samples with a well-defined elastic modulus using different AFMs revealed that the uncertainties in the determination of the deflection sensitivity and subsequently cantilever’s spring constant were the main sources of error. SNAP eliminates those errors by calculating the correct deflection sensitivity based on spring constants determined with a vibrometer. The procedure was validated within a large network of European laboratories by measuring the elastic properties of gels and living cells, showing that its application reduces the variability in elastic moduli of hydrogels down to 1%, and increased the consistency of living cells elasticity measurements by a factor of two. The high reproducibility of elasticity measurements provided by SNAP could improve significantly the applicability of cell mechanics as a quantitative marker to discriminate between cell types and conditions.

A hyaluronic acid/graphene oxide hydrogel for enhanced ex vivo expansion of cord blood-derived CD34+ cells

HA/GO hydrogels were prepared by methacrylated GO (MeGO) and methacrylated HA (MeHA) via an in-situ free radical polymerization, and then a series of HA/GO hydrogels with highly porous structure were obtained. All hydrogels exhibited excellent water absorption ability. Additionally, the elastic moduli of hydrogels were clearly enhanced by GO. CD34+ cells cultured on HA/GO-0.05 hydrogel showed higher expansion of CD34+ cells and CD34+CD38− cells compared to the other three hydrogels. Therefore, HA/GO-0.05 hydrogels have a potential for clinical-applied ex vivo expansion of hematopoietic stem cells.

Composite alginate gels for tunable cellular microenvironment mechanics.

The mechanics of the cellular microenvironment can be as critical as biochemistry in directing cell behavior. Many commonly utilized materials derived from extra-cellular-matrix create excellent scaffolds for cell growth, however, evaluating the relative mechanical and biochemical effects independently in 3D environments has been difficult in frequently used biopolymer matrices. Here we present 3D sodium alginate hydrogel microenvironments over a physiological range of stiffness (E = 1.85 to 5.29 kPa), with and without RGD binding sites or collagen fibers. We use confocal microscopy to measure the growth of multi-cellular aggregates (MCAs), of increasing metastatic potential in different elastic moduli of hydrogels, with and without binding factors. We find that the hydrogel stiffness regulates the growth and morphology of these cell clusters; MCAs grow larger and faster in the more rigid environments similar to cancerous breast tissue (E = 4–12 kPa) as compared to healthy tissue (E = 0.4–2 kpa). Adding binding factors from collagen and RGD peptides increases growth rates, and change maximum MCA sizes. These findings demonstrate the utility of these independently tunable mechanical/biochemistry gels, and that mechanical confinement in stiffer microenvironments may increase cell proliferation.

In situ forming gelatin hydrogel by fenton reaction for biomedical application

Event Abstract Back to Event In situ forming gelatin hydrogel by fenton reaction for biomedical application Joo Young Son1, Dong Hwan Oh1, Yunki Lee1, Kyung Min Park2 and Ki Dong Park1 1 Ajou University, Department of Molecular Science and Technology, Korea 2 Incheon National University, Division of Bioengineering, Korea Introduction: In situ crosslinkable hydrogels have received tremendous attention as a promising platform for tissue engineering and drug delivery. They can be injected into the target site via minimal invasive procedure and fill any irregular shapes of defects and tissues. In general, these hydrogels can be generated by various physical and chemical crosslinking reactions, including ionic interactions, hydrophobic interactions, Michael-type addition, photo-crosslinking and enzymatic reactions[1]. Among them, photo-initiation method is most frequently employed for the generation of hydrogels, however, this crosslinking system has still some limitations such as reagent toxicity, curing depth, and control of elastic modulus. In this study, the gelatin hydrogels were prepared via fenton reaction using FeCl2, H2O2 and ascorbic acid. Fe2+ is approved from FDA, and H2O2 are safer and easily available than photo-initiation[2]. It was demonstrated that the gelation time and elastic modulus of hydrogels could be easily adjusted by FeCl2 and H2O2 concentrations. This hydrogel using fenton reaction is biocompatible enough to use biomedical applications. Materials and Methods: Fig 1. Synthetic route and crosslinking of GelMA. Methacrylate grafted gelatin (GelMA) conjugates were synthesized by “epoxy-amine” click reaction between amine groups on gelatin and epoxy moiety on glycidyl methacrylate. The chemical structure of the GelMA was characterized by 1H NMR. The GelMA hydrogels were prepared in the presence of FeCl2, H2O2 and ascorbic acid. Thereafter, the physico-chemical properties (e.g., gelation time, mechanical strength and degradability) of hydrogels were characterized using a vial tilting method, rheological analysis and enzymatic degradation assay. In addition, in vitro cyto-compatibilty studies were carried out to evaluate cell viability using extracted solutions from the GelMA hydrogels. Results and Discussion: Fig 2. The picture of hydrogelation using fenton reaction (A) and the gelation time of GelMA hydrogels at various FeCl2 concentration (0.08~12.5 mmol/L) (B). The chemical structure of GelMA was confirmed by 1H NMR, demonstrating glycidyl methacrylate was sucessfully conjugated into gelatin. We evaluated the physico-chemical properties of the GelMA hydrogels, such as gelation time and mechanical strength. The gelation time (5 sec-22 mins) and the mechanical strength (1-8.4 kPa) were easily tuned, depending on the concentrations of FeCl2 and H2O2. When collagenase (2 U/mL) was treated, increaing H2O2 resulted in a faster degradation rate. It may be probably due to the higher crosslinking density. Furthemore, in vitro cell study was carried out to investigate the cyto-compatiblity of the GelMA hydrogels formed by fenton reaction (FeCl2 concentration; 3.13-12.5 mM). exhibiting excellent cyto-compatibility (cell viability; 88-94 %, TCPS; 100%). Conclusions We have developed in situ crosslinkable gelatin hydrogels. produced by crosslinking using fenton reaction. It was demonstrated that crosslinking density and rate of hydrogels were controlable by varying FeCl2 and H2O2 concentrations. The prepared GelMA hydrogels were shown to have exellent degradability and cyto-compatibility. We expect that the fenton reaction have potential as a crosslinking system to fabricate injectable biocompatible hydrogels for biomedical applications. This work was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) grant funded by the Ministry of Science, ICT & Future Planning (NRF-2015M3A9E2028577, 2015R1A2A1A14027221)

Determination of Elastic Modulus of Gelatin Gels by Indentation Experiments

Mechanical characterization of hydrogels is a challenging task because they are much softer than metals, ceramics or polymers. The elastic modulus of hydrogels is within 100-102kPa range. Because they easily break and slump under their own weight, tensile and bending tests are not suitable configurations to assess elastic modulus. This work reports on the determination of elastic modulus of a gelatin gel by indentation experiments. Indentation is very simple configuration, it is of technological importance and it can be applied at different length scales with high accuracy. The gelatin hydrogel behavior is first calibrated by uniaxial compression and low strain rheological measurements. It behaves as a hyperelastic solid with strain hardening capability at large strains and shows no dependence with frequency in the linear viscoelastic range. It can be properly characterized by the First order Ogden material model. Indentation experiments are carried out at macro and nanoscales using spherical and flat-ended cylindrical punches. Elastic contact solutions and inverse analysis accounting for hyperelasticity are used to extract the elastic modulus from experimental force-depth curves. Adhesion between punch and hydrogel influences the indentation response and affects the accuracy of elastic modulus determination in a larger extent than the assumption of linear elasticity. Adhesion leads to overestimation of elastic modulus values. The influence of adhesive forces increases with decreasing the length scale. A markedly decay of elastic modulus with increasing maximum load is observed at nanoscale. A hybrid model based on Hertz elastic contact solution and Johnson-Kendal-Roberts model for adhesion is used to determine elastic modulus. This model yields an elastic modulus in good agreement with that obtained from uniaxial compression test.

Swelling behaviours and mechanical properties of silk fibroin–polyurethane composite hydrogels

Abstract Silk fibroin–polyurethane (SF–PU) hydrogels combining advantages of the natural/synthetic materials were fabricated. FTIR was applied to characterize the structure of hydrogels. It was found that cross-linking network formed through chemical reactions between NCO groups on PU chain and NH 2 , OH groups on SF chains, in addition to the hydrogen bonding interactions. SEM was taken to observe the morphology of hydrogels, which exhibited a porous structure. Hydrogels demonstrated impressive swelling–deswelling behaviours and good sensitivities to temperature, ionic strength and pH. The swelling ratio of hydrogel could be as high as 4.37 and it decreased with the increase of SF contents. Due to that the diffusion exponent ( n ) was about 0.45, the initial swelling stage was thought to be controlled by the Fickian diffusion. For the whole swelling process, experimental results well fitted into the Schott second-order kinetic equation. Mechanical tests showed that the elastic modulus of hydrogels were about 0.558 MPa. Properties of hydrogels could be finely controlled so as to fulfill these potential biomedical applications, such as in Nucleus Pulposus Replacement or controlled drug release.

Anisotropy in elastic modulus of hydrogel containing magnetic particles

We derive the analytic expression of elastic modulus for a gel containing magnetic particles with a magnetic dipole moment. The obtained elastic modulus is anisotropic and the modulus increases and decreases with the density of magnetic particle when the direction of strain is perpendicular and parallel to the direction of magnetization, respectively. This behavior is qualitatively in good agreement with previous experimental data [T. Mitsumata, et al., Macromol. Rapid Commun. 23, (2002) 178].

Charge density dependence of elastic modulus of strong polyelectrolyte hydrogels

The mechanical behavior of a series of strong polyelectrolyte hydrogels based on acrylamide and 2-acrylamido-2-methylpropane sulfonic acid sodium salt (AMPS) was investigated. The hydrogels were prepared at a fixed crosslinker ratio and monomer concentration, but at various charge densities, i.e. AMPS contents between 0 and 100mol%. The elastic modulus of the hydrogels after their preparation first increases with increasing charge density but then decreases continuously. Investigation of the swollen state properties of the hydrogels shows existence of a large number of ionic groups inside the gel that are ineffective in gel swelling. The results indicate two opposite effects of charged groups on the elastic modulus of the hydrogels: formation of multiplets acting as additional crosslinks in the gel increases the elastic modulus of ionic hydrogels, whereas the effect of the electrostatic interaction of charged groups on elastic free energy decreases the modulus.