Storage Modulus Of Hydrogels Research Articles

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.

Tailoring the rheological properties of biosynthesized Copper oxide nanoparticles decorated Carboxymethyl cellulose hydrogels for biomedical applications

Nanoparticle-decorated hydrogels have seized substantial momentum in recent years, exclusively in biomedical research. In this investigation, Copper oxide nanoparticles decorated carboxymethyl cellulose hydrogels were prepared in an eco-friendly approach without using toxic cross-linkers. Initially, Copper oxide nanoparticles were prepared by biosynthesis approach to diminish the harmful effects of chemicals and to improve the biological activities using the leaf extract of Justicia adhatoda. The prepared nanoparticles were incorporated into the Carboxymethyl solution and carbopol to form a hydrogel by non-covalent interactions. X-ray diffraction analysis of CuO nanoparticles revealed a monoclinic crystalline structure without impurity. Rheological investigation of the pure hydrogel and CuO-decorated hydrogels revealed that CuO contributed to the enhancement of the hydrogel's mechanical performance. All the hydrogels demonstrated shear thinning behavior and better flow behavior index with the addition of CuO nanoparticles. The yield stress of the hydrogels was improved and found to be in the range of 61–79 Pa, which matches the ideal yield stress values in transdermal drug delivery. Storage moduli of hydrogels as a function of frequency was doubled (14–47.5 Pa), endorsing the involvement of CuO nanoparticles in crosslinking the polymeric matrix. Temperature and time sweep measurements revealed that the stability of the hydrogels also improved with the addition of CuO nanoparticles. The antibacterial activity of the hydrogels was evaluated using biofilm inhibition and showed better inhibition of 70 ± 0.5%, 75 ± 0.9%, 86 ± 0.8%, and 83 ± 0.8% against Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Enterococcus faecalis, respectively with increased concentration of CuO nanoparticles. The cell viability of the CuO-decorated hydrogels against MCF-7 and A431 was found to be 39% and 42%, respectively. Therefore, the eco-friendly biosynthesized CuO nanoparticles decorated hydrogels with improved mechanical properties can be employed in injectable and transdermal drug delivery systems.

Sustained neurotrophin-3 delivery from hyaluronic acid hydrogels for neural tissue regeneration.

The goal of this work was to design a polymer-based platform capable of localized, long-term delivery of biologically active neurotropic factors using an affinity-based approach. Here, we synthesized hyaluronic acid-methylfuran (HA-mF) hydrogels that provide sustained, affinity-based release of neurotrophin-3 (NT-3), a growth factor that promotes axon growth for 28 days. A Diels-Alder crosslinking reaction between HA-mF and polyethylene glycol (PEG)-dimaleimide occurs within 15 min under physiological conditions, resulting in hydrogels that can be polymerized in the presence of cells and growth factors. We also tuned the hydrogel's storage modulus to match that of native rat spinal cord tissue, providing a platform not only for localized drug delivery but also a suitable vehicle for cellular transplantation. The NT-3 released from the HAmF hydrogels remains bioactive for at least 14 days, promoting axonal growth from primary sensory neurons as well as stem cell-derived V2a interneurons and motoneurons in vitro. The hydrogels also supported cell growth allowing for 3-dimensional axonal extensions within the scaffold matrix. Here we confirm the protective role of HA-mF on matrix-bound NT-3 activity and show that these hydrogels are an excellent platform for growth factor delivery for neural applications.

Non-enzymatic glucose detection using free-standing gold nanoparticle loaded carrageenan hydrogel electrodes

The current manuscript reports the development of free-standing nanomaterial-modified hydrogels that can be explored for sensing applications. Most of the nanomaterial-hydrogel systems developed till now rely on the modification of an electrode as the supporting substrate on which the electrochemical reactions can take place. These substrates can be pencil electrodes and or screen-printed electrodes. This widely limits the use of hydrogels which can be used as scaffolds and can be explored for the fabrication of free-standing electrodes. Since the functionality of only hydrogel is quite limited the current manuscript reports the loading of gold nanoparticles inside the hydrogel matrix which makes it functionally active. The successful synthesis of the modified hydrogel was confirmed with Scanning Electron Microscopy (SEM) and elemental analysis. The rheological data confirmed the positive effect of gold loading on the hydrogel storage modulus. As a proof of concept, the work reports the non-enzymatic electrochemical detection of glucose using gold nanoparticle loaded carrageenan hydrogel. The sensor showed a linear response towards varying glucose concentrations (0 to 2.5 mM). The hydrogel systems can be incorporated into wearables and implantable sensors and can be extended for the detection of other biomarkers in bodily fluids.

Magneto-responsive hyaluronan hydrogel for hyperthermia and bioprinting: Magnetic, rheological properties and biocompatibility.

Magneto-responsive soft hydrogels are used for a number of biomedical applications, e.g., magnetic hyperthermia, drug delivery, tissue engineering, and neuromodulation. In this work, this type of hydrogel has been fabricated from hyaluronan (HA) filled with a binary system of Al2O3 nanoparticles and multicore magnetic particles (MCPs), which were obtained by clustering of superparamagnetic iron oxide FeOx NPs. It was established that the presence of diamagnetic Al2O3 has several positive effects: it enhances the hydrogel storage modulus and long-term stability in the cell cultivation medium; prevents the magnetic interaction among the MCPs. The HA hydrogel provides rapid heating of 0.3 °C per min under exposure to low amplitude radio frequency alternating magnetic field. Furthermore, the magneto-responsive hydrogel was successfully used to encapsulate cells and extrusion-based 3D printing with 87±6% cell viability, thus providing a bio-ink. The combination of high heating efficiency, softness, cytocompatibility, and 3D printability of magnetic HA hydrogel leads to a material suitable for biomedical applications.

Reinforcing supramolecular hyaluronan hydrogels via kinetically interlocking multiple-units strategy

Supramolecular hydrogels exhibit promising potential in biological and clinical fields due to their special dynamic properties. However, most existing supramolecular hydrogels suffer from poor mechanical strength, which severely limits their applications. Here in this study, the Kinetically Interlocking Multiple-Units (KIMU) strategy was applied to the hyaluronan networks by introducing different supramolecular interaction motifs in an organized and alternative manner. Our strategy successfully elevated the energy barrier of crosslinker dissociation to 103.0 kJ mol-1 and increased the storage modulus of hydrogels by 78 % with the intrinsic dynamic properties preserved. It can be expected that this method would bring a convenient and effective route to fabricate novel supramolecular materials with excellent mechanical properties.

Crosslinker structure modulates bulk mechanical properties and dictates hMSC behavior on hyaluronic acid hydrogels.

Synthetic hydrogels are attractive platforms due in part to their highly tunable mechanics, which impact cell behavior and secretory profile. These mechanics are often controlled by altering the number of crosslinks or the total polymer concentration in the gel, leading to structure-property relationships that inherently couple network connectivity to the overall modulus. In contrast, the native extracellular matrix (ECM) contains structured biopolymers that enable stiff gels even at low polymer content, facilitating 3D cell culture and permeability of soluble factors. To mimic the hierarchical order of natural ECM, this work describes a synthetic hydrogel system in which mechanics are tuned using the structure of sequence-defined peptoid crosslinkers, while fixing network connectivity. Peptoid crosslinkers with different secondary structures are investigated: 1) a helical, molecularly stiff peptoid, 2) a non-helical, less stiff peptoid, and 3) an unstructured, relatively flexible peptoid. Bulk hydrogel storage modulus increases when crosslinkers of higher chain stiffness are used. In-vitro studies assess the viability, proliferation, cell morphology, and immunomodulatory activity of human mesenchymal stem cells (hMSCs) on each hydrogel substrate. Matrix mechanics regulate the morphology of hMSCs on the developed substrates, and all of the hydrogels studied upregulate IDO production over culture on TCP. Softer substrates further this upregulation to a plateau. Overall, this system offers a biomimetic strategy for decoupling hydrogel storage modulus from network connectivity, enabling systematic study of biomaterial properties on hMSC behavior and enhancement of cellular functionality for therapeutic applications. STATEMENT OF SIGNIFICANCE: Various strategies to tune hydrogel mechanics have been developed to control human mesenchymal stem cell (hMSC) behavior and regulate their immunomodulatory potential. However, these strategies typically couple mechanics to network connectivity, which in turn changes other hydrogel properties such as permeability that may have unintended effects on hMSC behavior. This work presents a strategy to tune hydrogel mechanics using crosslinkers with different secondary structure and molecular rigidity. This strategy successfully decouples hydrogel moduli from crosslinker stoichiometry and mimics the hierarchical nature of the native extracellular matrix. The moduli of the developed hydrogels led to significant impacts on hMSC morphology and proliferation, and increased immunomodulatory potential, indicating that molecular rigidity is a promising avenue to control engineered ECM mechanics for therapeutic applications.

Porous synthetic hydrogel carrying basic fibroblast growth factor with controllable and rapid degradation rate to promote wound healing

Porous hydrogel dressings show breathability and possibility to carry and release basic fibroblast growth factor (bFGF) to promote wound healing. However, the difficult replacement may lead to the secondary damage. Thus, there is an urgent need to develop a method platform to control the degradation rate of hydrogel, so as to realize the on-demand replacement. The present study fabricated a porous hydrogel from co-polymized N,N′-bis(acryloyl) cystamine (BAC), allyl polyethylene glycol 500 (APEG500) and acrylic acid (AA) with the presence of polycaprolactone (PCL). BAC contains disulfide bond, which crosslinked the hydrogel. The pore size of the porous hydrogel was 400–600 μm. Higher content of BAC indicated higher crosslinking density, which reduced swelling ratio of hydrogel, while promoted hydrogel storage modulus. At the same time, the presence of PCL reduced swelling ratio of hydrogel, while promoted hydrogel mechanical properties, endowing hydrogel with tough feature. Porous hydrogels that crosslinked by disulfide bonds immersed in glutathione solution were found to degrade spontaneously and quickly due to the response to glutathione. Both crosslinking density and PCL content affected the degradation rate. The porous hydrogel carrying bFGF was applied to wound, promoting angiogenesis, thus accelerating wound healing within 12 d. Due to the spontaneous and rapid degradation of optimized porous hydrogel on wound within 3 days, there was no operation of removing dressing during treatment, avoiding damage during dressing replacement.

Laponite-Doped Poly(acrylic acid-co-acrylamide) Hydrogels

Electroacoustic characterization of soft nanocomposites has provided unique insights into the microstructure of soft nanocomposites, including nanoparticle (NP)-doped hydrogels and polyelectrolyte hydrogels without NPs. An outstanding problem is how to interpret the electrokinetic sonic amplitude (ESA) of charged hydrogels bearing charged NPs because both components generate an acoustic response to the electrical forcing. To this end, we study a series of Laponite XLG-doped, neutralized poly(acrylic acid-co-acrylamide) hydrogels, drawing principally on the ESA, electrical conductivity, and linear viscoelastic rheology. The hydrogel charge density was varied by the fraction of acrylic acid monomer fAAc = 0–1 while maintaining the total monomer concentration ≈8 wt % with Laponite concentration ≈0.85 wt %. Upon comparison of data from this study to those in a recent benchmark study of charged hydrogels without NPs, Laponite doping increased the electroacoustic signal and ionic conductivity but decreased the hydrogel storage modulus. Mechanistic theoretical models predicting how the real part of the ESA (at low frequency) and ionic conductivity of polyelectrolyte hydrogels depend on fAAc were extended to Laponite-doped hydrogels, together furnishing an estimate of the partial molar volume of acrylamide (in polymer form) that is close to the value for pure acrylamide (based on its density and molecular weight). The generally lower storage modulus with Laponite doping contrasts with previous studies of Laponite-doped polyacrylamide and poly(acrylic acid) hydrogels and solutions. This seems to reflect the high degree of neutralization, which transforms an attraction between protonated carboxyl moieties and Laponite to an electrostatic repulsion. The hindering effects of polymerization and cross-linking on acrylic acid-co-acrylamide networks were also investigated by comparing the ESA and conductivity of hydrogels with their monomer solution counterparts. Systematically varying the ratio of charged to uncharged monomers, with and without chemical cross-linking, provides insights to benefit a broad range of technological applications for hydrogel nanocomposites.

Ultrasound-triggered transglutaminase-catalyzed egg white-bovine gelatin composite hydrogel: Physicochemical and rheological studies

The present paper investigated gel properties and secondary structures of egg white-bovine gelatin composite hydrogels with different mass ratios upon ultrasound and transglutaminase pretreatment. The free sulfhydryl content increased with increasing gelatin in proteins mass ratio; however, longer probe sonication had an opposite effect on free sulfhydryl content and hydrogel solubility. The hydrogel solubility data revealed that proteins ratio and the pretreatment conditions (ultrasound duration and transglutaminase concentration) determined the contribution of non-covalent bonds (including electrostatic bonds, hydrogen bonds, and hydrophobic interactions) and covalent bonds (i.e., SS bridges) in the formation of composite hydrogels. Moreover, the hardness and storage modulus of hydrogels were improved with increasing gelatin in proteins mass ratio and ultrasound duration. Based on Fourier transform infrared spectroscopy and rheological data, helical structures had a great portion in composite hydrogels. Finally, the microstructure investigations showed that hydrogels formed the most porous structures at 50E:50G and 40E:60G (E: egg, G: gelatin) mass ratios.

Tannic acid/clay hydrogel with time-dependent mechanical and adhesive performance enabled by molecular interaction evolution

The investigation on dynamic molecular mechanisms is of importance for developing smart materials for various applications. Herein, we report a dynamic tannic acid (TA)/clay hydrogel with time-dependent mechanical and adhesive performance, in which clay plays an important role in regulating the molecular interaction evolution of hydrogels. Specifically, TA mediated the assembly of clay to form networked hydrogels driven by TA-clay dynamic interactions. Afterwards, clay served as a pro-oxidant component accelerated covalent crosslinking reactions of TA. Consequentially, the hydrogel transitioned from reversible dynamic networks to irreversible covalent networks over the time. Owing to the molecular interaction evolution, storage modulus of hydrogels gradually increased from 22 Pa to 3235 Pa in 4 days. Adhesive strength between hydrogels and iron substrates increased from 3 MPa to 23 MPa in 12 h and then decreased to 5 MPa. This finding will be a general principle for designing dynamic materials with time-dependent physicochemical properties and will enable various applications such as customized temporary adhesives.

Fast and Highly Efficient Adsorption Removal of Toxic Pb(II) by a Reusable Porous Semi-IPN Hydrogel Based on Alginate and Poly(Vinyl Alcohol).

A porous semi-interpenetrating network (semi-IPN) hydrogel adsorbent with excellent adsorption properties and removal efficiency towards Pb(II) was prepared by a facile grafting polymerization reaction in aqueous medium using natural biopolymer sodium alginate (SA) as the main chains, sodium acrylate (NaA) as the monomers, and poly(vinyl alcohol) (PVA) as the semi-IPN component. FTIR, TGA and SEM analyses confirm that NaA monomers were grafted onto the macromolecular chains of SA, and PVA chains were interpenetrated and entangled with the crosslinked network. The incorporation of PVA facilitates to form pores on the surface of hydrogel adsorbent. The semi-IPN hydrogel containing 2 wt% of PVA exhibits high adsorption capacity and fast adsorption rate for Pb(II). The best adsorption capacity reaches 784.97 mg/g, and the optimal removal rate reaches 98.39% (adsorbent dosage, 2 g/L). In addition, the incorporation of PVA improved the gel strength of hydrogel, and the storage modulus of hydrogel increased by 19.4% after incorporating 2 wt% of PVA. The increase of gel strength facilitates to improve the reusability of hydrogel. After 5 times of regeneration, the adsorption capacity of SA-g-PNaA decreased by 23.2%, while the adsorption capacity of semi-IPN hydrogel only decreased by 10.8%. The adsorption kinetics of the hydrogel in the initial stage (the moment when the adsorbent contacts solution) and the second stage are fitted by segmentation. It is intriguing that the adsorption kinetics fits well with both pseudo-second-order kinetic model and pseudo-first-order model before 60 s, while only fits well with pseudo-second-order adsorption model in the whole adsorption process. The chemical complexing adsorption mainly contribute to the efficient capturing of Pb(II).

Controlling Nucleopeptide Hydrogel Self-Assembly and Formation for Cell-Culture Scaffold Applications.

Hydrogels made from self-assembling peptides have significant advantages in tissue engineering, namely a biocompatible nature and large molecular repertoire. Short peptides in particular allow for straightforward synthesis, self-assembly, and reproducibility. Applications are currently limited, however, due to potential toxicity of the chemical modifications that drive self-assembly and harsh gelation conditions. Peptides conjugated to nucleobases present one opportunity for a naturally derived species to minimize cytotoxicity. We have developed a hydrogel-formation environment for nucleopeptide gelation modulated entirely by biological buffers and salts. Self-assembly in this system is dependent on buffer and ion identity mediated by pKa and formulation in the former and by valency and ionicity in the latter. Solutions at physiological pH and osmolarity, and in turn compatible with cell culture, initiate hydrogel formation and analytical and computational methods are used to explore pH and salt effects at the molecular and structural level. The mechanism of nucleopeptide self-assembly enables tuning of mechanical properties through the addition of divalent cations and one order of magnitude increase in hydrogel storage modulus. The stability of these constructs therefore provides an opportunity for long-term cell culture, and we demonstrate survival and proliferation of fibroblasts on hydrogel surfaces. This novel, biological buffer-mediated gelation methodology expands opportunities for tissue engineering applications of short peptides and their derivatives.

Alginate-magnetic short nanofibers 3D composite hydrogel enhances the encapsulated human olfactory mucosa stem cells bioactivity for potential nerve regeneration application

The design of 3D hydrogel constructs to elicit highly controlled cell response is a major field of interest in developing tissue engineering. The bioactivity of encapsulated cells inside pure alginate hydrogel is limited by its relatively inertness. Combining short nanofibers within a hydrogel serves as a promising method to develop a cell friendly environment mimicking the extracellular matrix. In this paper, we fabricated alginate hydrogels incorporating different magnetic short nanofibers (M.SNFs) content for olfactory ecto-mesenchymal stem cells (OE-MSCs) encapsulation. Wet-electrospun gelatin and superparamagnetic iron oxide nanoparticles (SPIONs) nanocomposite nanofibers were chopped using sonication under optimized conditions and subsequently embedded in alginate hydrogels. The storage modulus of hydrogel without M.SNFs as well as with 1 and 5 mg/mL of M.SNFs were in the range of nerve tissue. For cell encapsulation, OE-MSCs were used as a new hope for neuronal regeneration due to their neural crest origin. Resazurin analyses and LIVE/DEAD staining confirmed that the composite hydrogels containing M.SNFs can preserve the cell viability after 7 days. Moreover, the proliferation rate was enhanced in M.SNF/hydrogels compared to alginate hydrogel. The presence of SPIONs in the short nanofibers can accelerate neural-like differentiation of OE-MSCs rather than the sample without SPIONs.

Self-healable soft shield for \u03b3-ray radiation based on polyacrylamide hydrogel composites

With the growing risk of radiation exposure, there are growing interests in radiation shielding. Because most radiation shields are made from heavy metals, a need to develop a soft shield is raised to protect human body. However, because the shield can easily undergo a mechanical damage by an impact, it would be better to have self-repairing system in the shield. Here, we have fabricated an intrinsic self-healable soft shield for gamma ray by making acrylamide based hydrogel composite. The composite contains lead dioxide nanoparticles for gamma ray shielding and Laponite clays for self-repairing. Although the hydrogel contained a large amount of lead dioxide nanoparticles (3.23 M), the fabricated composites stretched beyond 1400% while showing a high attenuation coefficient of 0.1343 cm−1 against gamma ray from a cobalt-60 source. Then a systematic study was performed to analyze self-healing properties and the 96.55% of maximum self-healing efficiency was obtained. We also analyzed a storage modulus of hydrogel and molecular weight of polyacrylamide to study an effect of gamma ray on the self-healing. The self-healing efficiency was decreased by a gamma ray because the radiation induces scissioning or covalent crosslinking in the chains.

Real-time monitoring of hydrogel rheological property changes and gelation processes using high-order modes of cantilever sensors

Here, we report that high-order modes of dynamic-mode piezoelectric cantilever sensors near 1 MHz persist in hydrogels and enable sensitive characterization of hydrogel viscoelastic properties and real-time monitoring of rheological property changes. Continuous tracking of the resonant frequency (fn), phase angle and impedance at resonance, and quality factor (Qn) of low- and high-order modes in piezoelectric-excited milli-cantilever (PEMC) sensors enabled the characterization of hydrogel viscoelastic properties and real-time monitoring of gelation processes (fair, low = 38.1 kHz and fair, high = 836.9 kHz). Various spectral features of the sensor's impedance response, including changes in fn, phase angle, Qn, and impedance, enabled sensing of changes in alginate and polyethylene glycol dimethacrylate (PEGDMA) hydrogel composition and low-frequency viscoelastic properties characterized by DMA across the 0.5–4 wt. % and 8–18 wt. % concentration ranges, respectively. The phase angle and impedance responses exhibited the highest sensitivities to changes in alginate and PEGDMA hydrogel storage modulus (E′) and loss factor [tan(δ)]. High-order modes exhibited an increased dynamic range upper limit (33.2 kPa) and reduced limit of detection (90 Pa) for the detection of changes in E′ relative to low-order modes (23.4 kPa and 230 Pa, respectively). This work suggests that high-order modes of PEMC sensors near 1 MHz compliment low-order modes in the 1–100 kHz frequency range for sensitive characterization and real-time monitoring of hydrogel rheological properties across a wide frequency range. Millimeter-scale piezoelectric cantilever sensors appear to be a promising characterization and processing tool for hydrogel materials research.

All-Polysaccharide, Self-Healing Injectable Hydrogels Based on Chitosan and Oxidized Hydroxypropyl Polysaccharides.

Polysaccharide-based hydrogels are attractive materials for biomedical applications for reasons that include their polyfunctionality, generally benign nature, and biodegradability. However, the use of polysaccharide-based hydrogels may be limited by toxicity arising from small-molecule crosslinkers, or may involve undesired chemical modification [Hennink, W. E.; et al. Adv. Drug Delivery Rev. 2012, 64, 223-236]. Here, we report a green, simple, efficient strategy for the preparation of polysaccharide-based, in situ forming hydrogels. The Edgar group reports in the accompanying manuscript that chemoselective oxidation of oligo(hydroxypropyl)-substituted polysaccharides introduces ketone groups at the termini of the side chains [Nichols, B. L. B.; et al]. Amine-containing moieties can condense with ketones to form imines. The imine linkage is dynamic in the presence of water, providing the potential for self-healing [Wei, Z.; et al. Adv. Funct. Mater. 2015, 25, 1352-1359], injectability [Wei, Z.; et al. Adv. Funct. Mater. 2015, 25, 1352-1359], and pH responsiveness [Yao, K.; et al. J. Appl. Polym. Sci. 1993, 48, 343-354]. In this work, we designed and prepared two different types of hydrogels, oxidized hydroxypropyl cellulose/chitosan (Ox-HPC-Chitosan) and oxidized hydroxypropyl dextran/chitosan (Ox-HPD-Chitosan), each cross-linked by imine bonds. The mechanical properties of these hydrogels were characterized by rheometry, revealing that hydrogel storage modulus could be tuned from 300 Pa to 13 kPa simply by controlling the degree of substitution (DS) of ketone groups. Rheological characterization also illustrated the rapid self-healing property of these all-polysaccharide hydrogels. Moreover, these hydrogels exhibited high swelling rates and facile injectability. Therefore, this work reveals a potential strategy for the construction of hydrogels that require no small-molecule crosslinkers and are therefore highly attractive for biomedical, agricultural, controlled release, and other applications.

Real-time characterization of hydrogel viscoelastic properties and sol-gel phase transitions using cantilever sensors

Here, we report for the first time that resonance in dynamic-mode cantilever sensors persists in hydrogels and enables the real-time characterization of hydrogel viscoelastic properties and the continuous monitoring of sol-gel phase transitions (i.e., gelation and dissolution processes). Real-time tracking of piezoelectric-excited millimeter cantilever (PEMC) sensor resonant frequency (fair = 55.4 ± 8.8 kHz; n = 5 sensors) and quality factor (Q; Qair = 23.8 ± 1.5) enabled continuous monitoring of high-frequency hydrogel shear storage and loss moduli (G′f and G″f, respectively) calculated by sensor data and fluid–structure interaction models. Changes in the sensor phase angle, quality factor, and high-frequency shear moduli obtained at the resonant frequency (G′f and G″f) correlated with low-frequency moduli obtained at 1 Hz using dynamic mechanical analysis. Characterization studies were performed using physically and chemically crosslinked hydrogel systems, including gelatin hydrogels (6–10 wt. %) and alginate hydrogels (0.25–0.75 wt. %). The sensor exhibited a dynamic range from the rheological properties of inviscid solutions to hydrogels with high-frequency moduli of 80 kPa and low-frequency moduli of 26 kPa. The sensor exhibited a limit of detection of 260 Pa and 1.9 kPa for changes in hydrogel storage modulus (E′) based on the sensor’s phase angle and quality factor responses, respectively. We also show that sensor data enable quantitative characterization of gelation process dynamics using a modified Hill model. This work suggests that cantilever sensors provide a promising platform for the sensor-based characterization of hydrogels, such as quantification of viscoelastic properties and real-time monitoring of gelation processes.

Mechanical Characteristics of SPG-178 Hydrogels: Optimizing Viscoelastic Properties through Microrheology and Response Surface Methodology

Background:SApeptides have growing applications in tissue engineering and regenerative medicine. The application of SApeptide-based hydrogels depends strongly on their viscoelastic properties. Optimizing the properties is of importance in tuning the characteristics of the hydrogels for a variety of applications. Methods:In this study, we employed statistical modeling, conducted with the RSM and particle tracking microrheology, to investigate the effects of self-assembling SPG-178 peptide and added NaCl salt concentrations and milieu type (DI water or blood serum) on the viscoelastic properties of SPG-178 hydrogels. A central composite RSM model was employed for finding the optimum value of the parameters to achieve the highest storage modulus and the lowest tan δ. Results:Viscoelastic properties of each sample, including storage modulus, loss modulus, and tan δ, were determined. Storage modulus and tan δ were modeled, accounting for the impact of the SPG-178 peptide and NaCl concentrations and milieu type on the viscoelastic properties. It was found that the SPG-178 hydrogel storage modulus was positively influenced by the SPG-178 peptide concentration and the serum.Conclusion:A combination of microrheology and RSM is a useful test method for statistical modeling and analysis of rheological behavior of solid-like gels, which could be applied in various biomedical applications such as hemostasis.

Biodegradable biopolymer network structures to create delayed burst digestive release of encapsulated lipids

This study sought to investigate whether encapsulation of lipids in core-shell hydrogel structures of tailored shell porosity could create a delayed burst release of encapsulated lipids, and examined the underpinning mechanisms. We demonstrated that gastrointestinal digestion of core-shell structures resulted in a delay in the onset of lipid digestion, without affecting lipid digestion kinetics. Systematic increase in hydrogel protein content above 65 g/L lead to an exponential increase in digestive delay (250 min). Whilst an increase in xanthan content between 5 and 9 g/L lead to a modest decrease in digestive delay (40 min). Rheological investigations revealed a linear relationship between hydrogel storage modulus G′ and digestive breakdown delay (T1/2). Given that G’ is directly related to hydrogel mesh size, this result suggests that the main factor controlling the timing of digestive release is the average mesh size of the outer protein hydrogel. A kinetic model was created to describe the delayed burst release behaviour of encapsulated lipids and successfully predicted the influence of shell thickness, shell protein density on the timing of gastro-intestinal release (in vitro). By combining microstructural/rheological experiments with in vitro digestive studies we have understood the main factors controlling the digestive breakdown of hierarchical biopolymer hydrogels. We could successfully miniaturise these core-shell structures so they would easily empty from the stomach whilst maintaining programmable delayed burst release. We have created a novel family of core-shell hydrogel oral dosage forms for the delivery of poorly soluble drugs and the programmed delivery of lipids within the gut.