Hydrogel Mesh Size Research Articles

Matrix metalloproteinase 9-activatable peptide-conjugated hydrogel-based fluorogenic intraocular-lens sensor

The eye is an extension of the central nervous system (CNS) and contains aqueous humor (AH), which is a fluid rich in biomolecules secreted from intraocular tissues; thus, this organ allows for non-invasive visualization of early changes in CNS disorders. There is a growing interest in developing implantable devices, such as intraocular-lens (IOL), for specific medical uses, including intraocular monitoring. We describe a novel IOL-sensing system for detecting AH biomarkers via biocompatible enzyme-activatable fluorogenic hydrogel sensors. Matrix-metalloproteinase-9, a biomarker of degenerative CNS and eye disorders, was selected as a target. A peptide-probe-incorporated fluorogenic IOL (FIOL) was developed using diacrylamide-group-modified poly(ethyleneglycol) (PEGDAAm) biocompatible hydrogels, adjusting the hydrogel mesh size to allow selective penetration of the target while blocking non-targets, using label-free detection with semi-permanently implantable sensors, and demonstrating the clinical feasibility of FIOL through in vivo testing. This novel FIOL-based sensing system represents a promising approach for liquid biopsy of intraocular fluids.

Hydrogel compression and polymer osmotic pressure

Controlling the elastic modulus of simple synthetic hydrogels like polyacrylamide is essential to their use in many areas of biotechnology, including tissue engineering, medical device development, and drug delivery applications. Indentation-based methods for measuring hydrogel elastic moduli are preferred over measurements in shear rheometers or tensile testing instruments when the freedom to choose sample volume and shape are restricted; contact lenses represent such an example. It is often believed that the local application of indentation loads will volumetrically compress hydrogels, increasing the sample's polymer concentration even when the applied pressure is less than the hydrogel's osmotic pressure. Here, we test this idea by volumetrically compressing polyacrylamide hydrogels of different compositions while measuring the degree of compression with increasing applied pressure. Our results reveal that at applied pressures below the hydrogel osmotic pressure, the gels exhibit only marginal compression, while above the osmotic pressure the gels compress as predicted by classical polymer physics theory. Combining measurements of osmotic pressure and polymer mesh size, we determine the scaling relationships between hydrogel composition, mesh size, and osmotic pressure. By demonstrating agreement between experiment and theory, we use our measurements to determine the Kuhn length of the individual polymer chains constituting the hydrogels.

Computational-Based Design of Hydrogels with Predictable Mesh Properties.

Hydrogel systems are an appealing class of therapeutic delivery vehicles, though it can be challenging to design hydrogels that maintain desired spatiotemporal presentation of therapeutic cargo. In this work, we propose a different approach in which computational tools are developed that creates a theoretical representation of the hydrogel polymer network to design hydrogels with predefined mesh properties critical for controlling therapeutic delivery. We postulated and confirmed that the computational model could incorporate properties of alginate polymers, including polymer content, monomer composition and polymer chain radius, to accurately predict cross-link density and mesh size for a wide range of alginate hydrogels. Additionally, the simulations provided a robust strategy to determine the mesh size distribution and identified properties to control the mesh size of alginate hydrogels. Furthermore, the model was validated for additional hydrogel systems and provided a high degree of correlation (R2 > 0.95) to the mesh sizes determined for both fibrin and polyethylene glycol (PEG) hydrogels. Finally, a full factorial and Box-Behnken design of experiments (DOE) approach utilized in combination with the computational model predicted that the mesh size of hydrogels could be varied from approximately 5 nm to 5 μm through controlling properties of the polymer network. Overall, this computational model of the hydrogel polymer network provides a rapid and accessible strategy to predict hydrogel mesh properties and ultimately design hydrogel systems with desired mesh properties for potential therapeutic applications.

Influence of Loading Conditions and Temperature on Static Friction and Contact Aging of Hydrogels with Modulated Microstructures.

Biological tribosystems enable diverse functions of the human body by maintaining extremely low coefficients of friction via hydrogel-like surface layers and a water-based lubricant. Although stiction has been proposed as a precursor to damage, there is still a lack of knowledge about its origin and its relation to the hydrogel's microstructure, which impairs the design of soft matter as replacement biomaterials. In this work, the static friction of poly(acrylamide) hydrogels with modulated composition was investigated by colloidal probe lateral force microscopy as a function of load, temperature, and loading time. Temperature-dependent studies enable to build a phase diagram for hydrogel's static friction, which explains stiction via (polymer) viscoelastic and poroelastic relaxation, and a subtle transition from solid- to liquid-like interfacial behavior. At room temperature, the static friction increases with loading time, a phenomenon called contact aging, which stems from the adhesion of the polymer to the colloid and from the drainage-induced increase in contact area. Contact aging is shown to gradually vanish with increase in temperature, but this behavior strongly depends on the hydrogel's composition. This work scrutinizes the relation between the microstructure of hydrogel-like soft matter and interfacial behavior, with implications for diverse areas of inquiry, not only in biolubrication and biomedical applications but also in soft robotics and microelectromechanical devices, where the processes occurring at the migrating hydrogel interface are of relevance. The results support that modulating both the hydrogel's mesh size and the structure of the near-surface region is a means to control static friction and adhesion. This conceptual framework for static friction will foster further understanding of the wear of hydrogel-like materials.

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.

Thaw-Induced Gelation of Alginate Hydrogels for Versatile Delivery of Therapeutics.

Alginate hydrogels have been extensively used and successfully validated as delivery vehicles of bioactive factors in many tissue engineering applications. This work describes and characterizes a singular alternative method to create alginate hydrogels designated as thaw-induced gelation (TIG). The TIG method involves gelation through the time-dependent release of the polymer or crosslinker by melting into solution. Alginate TIG hydrogels were validated for spatial-temporal control delivery of different cargos including albumin, dextran, and doxorubicin. Chitosan was incorporated into TIG hydrogels to investigate the electrostatic interactions between alginate and the tested cargos. Interestingly, while 90% of doxorubicin was released after 8h from hydrogels formed with frozen calcium, hydrogels formulated from frozen alginate took 72h. In addition, the storage modulus of TIG hydrogels prepared from frozen alginate was double that of a hydrogel formed without freezing alginate. Therefore, the utility of TIG strategies are particularly promising for the delivery of therapeutic cargos smaller than the mesh size of the alginate hydrogel, as it enables controlled release of these cargos without any further chemical modifications of the hydrogels. These TIG alginate hydrogels with tunable mechanical properties and control over the delivery of smaller cargos could be useful in many tissue engineering applications.

Characterization of the microstructure of hydrazone crosslinked polysaccharide-based hydrogels through rheological and diffusion studies

Microstructure plays an essential role in the control of hydrogel properties. It is also an important factor when cells or drugs are encapsulated inside the hydrogel. In this work, the microstructures of hydrazone crosslinked hyaluronan-, alginate- and gellan gum-based hydrogels were evaluated thoroughly for the first time by using rheology- and diffusion (fluorescence recovery after photobleaching, FRAP)-based methods. The effect of gel parameters on the viscoelastic and diffusion properties of hydrogels, and further on their structural parameters (mesh size, average molecular weight of the polymer chain between neighboring crosslinks, crosslinking density) are shown. Results further show that diffusivity decreased when larger dextran sizes were used, which were equivalent to the mesh sizes of hydrogels (15 nm to 47 nm) evaluated by the rheological method. This mesh size range allows the transportation of smaller molecules, but also peptides and most of the proteins. A correlation between the storage modulus and the structural parameters was also shown. Overall, hydrazone crosslinking offers an easy way to produce polysaccharide-based hydrogels with variable microstructures by altering the gel parameters.

Heating efficiency of magnetic nanoparticles decreases with gradual immobilization in hydrogels

Abstract Magnetic nanoparticles (MNP) applied in magnetic fluid hyperthermia cancer treatment interact with cancerous tissue in various ways. The impact of these interactions on MNP heating efficiency is hard to quantify and strongly depends on the MNP mobility inside the cancerous environment. There, this MNP mobility is inhibited by cell attachment and internalization. In this study, we model this impact and analyze the MNP heating under gradual immobilization of MNP in acrylamide hydrogels with tailored mesh size. Our results confirm a clear particle heating dependency on the state of immobilization of MNP. This state is related to the mean mesh size of the respective hydrogel. From this, the contributions of Brownian and Neel relaxation mechanisms to the overall particle heating are estimated. In fact, the heating efficiency decreases by up to 35% for the highest immobilization state of MNP. This result is discussed in the context of the field-dependent Brownian and Neel relaxation time, showing that the former significantly contributes to the heating efficiency even for small particles under the field parameters employed in this study.

SERS-Active-Charged Microgels for Size- and Charge-Selective Molecular Analysis of Complex Biological Samples.

Surface-enhanced Raman scattering (SERS) provides a dramatic increase of Raman intensity for molecules adsorbed on nanogap-rich metal nanostructures, serving as a promising tool for molecular analysis. However, surface contamination caused by protein adsorption and low surface concentration of small target molecules reduce the sensitivity, which severely restricts the use of SERS in many applications. Here, charged microgels containing agglomerates of gold nanoparticles (Au NPs) are designed using droplet-based microfluidics to provide a reliable SERS substrate with molecular selectivity and high sensitivity. The limiting mesh size of hydrogel enables the autonomous exclusion of large proteins and the charged matrix concentrates oppositely charged small molecules through electrostatic attraction. As nanogaps among Au NPs in the agglomerates enhance Raman intensity, Raman spectrum of the adsorbed molecules is selectively measured with high sensitivity in the absence of interruption from adhesive proteins. Therefore, the SERS-active-charged microgels can be used for direct analysis of pristine biological samples without the pretreatment steps of separation and concentration, which are commonly a prerequisite for Raman analysis. For the purpose of demonstration, a direct detection of fipronil sulfone with partial negative charges, a metabolite of toxic insecticide, dissolved in eggs using the positively charged microgels without any pretreatment of the samples, is shown.

Chemically Modified Hydrogel-Filled Nanopores: A Tunable Platform for Single-Molecule Sensing.

Label-free, single-molecule sensing is anideal candidate for biomedical applications that rely on the detection of low copy numbers in small volumes and potentially complex biofluids. Among them, solid-state nanopores can be engineered to detect single molecules of charged analytes when they are electrically driven through the nanometer-sized aperture. When successfully applied to nucleic acid sensing, fast transport in the range of 10-100 nucleotides per nanosecond often precludes the use of standard nanopores for the detection of the smallest fragments. Herein, hydrogel-filled nanopores (HFN) are reported that combine quartz nanopipettes with biocompatible chemical poly(vinyl) alcohol hydrogels engineered in-house. Hydrogels were modified physically or chemically to finely tune, in a predictable manner, the transport of specific molecules. Controlling the hydrogel mesh size and chemical composition allowed us to slow DNA transport by 4 orders of magnitude and to detect fragments as small as 100 base pairs (bp) with nanopores larger than 20 nm at an ionic strength comparable to physiological conditions. Considering the emergence of cell-free nucleic acids as blood biomarkers for cancer diagnostics or prenatal testing, the successful sensing and size profiling of DNA fragments ranging from 100 bp to >1 kbp long under physiological conditions demonstrates the potential of HFNs as a new generation of powerful and easily tunable molecular diagnostics tools.

DNA molecules deviate from shortest trajectory when driven through hydrogel.

Dynamic fluorescence-based single-molecule imaging of λ-DNA molecules driven through agarose hydrogels by DC electric fields reveals that passage through the hydrogel (98.5% water content) induces mobility orthogonal to the external field. Tortuous paths followed by the DNA molecules, which are heavily entangled in the hydrogel mesh as their contour length is nearly 100 times the hydrogel mesh size of 200 nm, cause them to appear to diffuse orthogonal to the driving force. The higher the driving field, from 2 to 16 V/cm, the higher the off-axis dispersion is, over the same time interval. We measure the off-axis displacement distribution over 3 orders of magnitude of probability density and find a master curve after normalizing for time (t) elapsed, but the power of time for normalizing increases with the external field, from t0.25 to t0.6 with increasing field. Comparing trajectories over the same distance traveled in the electric field direction, we observe whereas for the highest field strengths DNA molecules come closest to taking the shortest trajectory between two points in space, deviations from the shortest trajectory grow larger and larger (up to 40% larger) as one approaches the case of small yet finite external field strength.

Adjustable Tribological Behavior of Glucose-Sensitive Hydrogels.

Stimuli-responsive hydrogels have been considered to have various applications in numerous fields. In the present work, a double-network (DN) hydrogel has been synthesized. The copolymers of 2-acrylamide-2-methylpropane sulfonic acid (AMPS) and acrylamide (AM) [P(AMPS- co-AM)] are prepared as the 1st network and poly(acrylic acid) as the 2nd network. This DN hydrogel is sensitive to glucose by introducing the glucose-sensitive group phenylboronic acid to the network. The tribological properties of this glucose-sensitive DN hydrogel have been investigated using a universal mechanical tester (UMT-5). The tribological results show that the friction coefficient varied with the glucose solution. The friction coefficient increased to a maximum of 0.06, and finally decreased to 0.025 with the increase in the glucose concentration. An adjustable friction coefficient of the hydrogel, between 0.025 and 0.056, was achieved along with the change of lubricant. According to the tribological experimental results and the analysis of the DN structure, it can be deduced that a hydrated layer exists in the interface of the hydrogel. The hydrated layers consisting of water molecules are bounded with the hydrophilic group of the hydrogel network by hydrogen bonds. The change in the number of water molecules leads to the difference in the water content of the hydrogel, which further resulted in the various tribological properties. In addition, the hydrogel's mesh size also has an impact on the change in friction coefficient. In general, the adjustable friction of the hydrogel in a glucose environment is achieved.

An improved correlation to predict molecular weight between crosslinks based on equilibrium degree of swelling of hydrogel networks.

Accurate characterization of hydrogel diffusional properties is of substantial importance for a range of biotechnological applications. The diffusional capacity of hydrogels has commonly been estimated using the average molecular weight between crosslinks (Mc ), which is calculated based on the equilibrium degree of swelling. However, the existing correlation linking Mc and equilibrium swelling fails to accurately reflect the diffusional properties of highly crosslinked hydrogel networks. Also, as demonstrated herein, the current model fails to accurately predict the diffusional properties of hydrogels when polymer concentration and molecular weight are varied simultaneously. To address these limitations, we evaluated the diffusional properties of 48 distinct hydrogel formulations using two different photoinitiator systems, employing molecular size exclusion as an alternative methodology to calculate average hydrogel mesh size. The resulting data were then utilized to develop a revised correlation between Mc and hydrogel equilibrium swelling that substantially reduces the limitations associated with the current correlation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1339-1348, 2018.

Design of nonionic micelle-laden polysaccharide hydrogels for controlled delivery of hydrophobic drugs

The incorporation of micelle self-assembly in hydrogels has been used to produce self-healing materials, materials with tunable mechanical properties, and hydrophilic or hydrophobic drug delivery systems. However, little is known about the connection among formulation – structure – properties (particularly transport) in these systems. This connection is explored in alkyl ethoxylate micelle-laden gellan gum hydrogels used as delivery system for the hydrophobic drug dexamethasone. Phase behavior maps and rheological characterization of the micelle-laden hydrogels indicate that their properties are largely dominated by the concentration and cloud point (CP) of the alkyl ethoxylate nonionic surfactant. The sol-gel temperature of the hybrid hydrogels was found to be close to the CP of the surfactant, and their storage modulus (G’) was found to increase with increasing surfactant concentration. A detailed analysis of the phase behavior maps, and evaluations of the mesh size of the hybrid hydrogels suggest a novel mechanism whereby micelles associate with gellan gum strands during high temperature hydration, hindering the double-helix assembly of the strands upon cooling. This increases the number of single strands and the density of physical cross-links, reducing the mesh size of the hydrogel. This mesh size reduction led to a decrease in the effective diffusion coefficient of micelles in the gel, and extended the release time of dexamethasone from 2h in surfactant-free hydrogel to more than 2days in the micelle-laden hydrogel.

Establishment of a Physical Model for Solute Diffusion in Hydrogel: Understanding the Diffusion of Proteins in Poly(sulfobetaine methacrylate) Hydrogel.

Prediction of the diffusion coefficient of solute, especially bioactive molecules, in hydrogel is significant in the biomedical field. Considering the randomness of solute movement in a hydrogel network, a physical diffusion RMP-1 model based on obstruction theory was established in this study. The physical properties of the solute and the polymer chain and their interactions were introduced into this model. Furthermore, models RMP-2 and RMP-3 were established to understand and predict the diffusion behaviors of proteins in hydrogel. In addition, zwitterionic poly(sulfobetaine methacrylate) (PSBMA) hydrogels with wide range and fine adjustable mesh sizes were prepared and used as efficient experimental platforms for model validation. The Flory characteristic ratios, Flory-Huggins parameter, mesh size, and polymer chain radii of PSBMA hydrogels were determined. The diffusion coefficients of the proteins (bovine serum albumin, immunoglobulin G, and lysozyme) in PSBMA hydrogels were studied by the fluorescence recovery after photobleaching technique. The measured diffusion coefficients were compared with the predictions of obstruction models, and it was found that our model presented an excellent predictive ability. Furthermore, the assessment of our model revealed that protein diffusion in PSBMA hydrogel would be affected by the physical properties of the protein and the PSBMA network. It was also confirmed that the diffusion behaviors of protein in zwitterionic hydrogels can be adjusted by changing the cross-linking density of the hydrogel and the ionic strength of the swelling medium. Our model is expected to possess accurate predictive ability for the diffusion coefficient of solute in hydrogel, which will be widely used in the biomedical field.

Scaling laws of gelatin hydrogels for steady dynamic friction

In this article, we use population balance based dynamic friction model for steady sliding to develop scaling laws in the terms of mesh size of gelatin hydrogels. First of all, it is observed in the sliding experiments that shear modulus of gelatin hydrogels depends on sliding velocity. This dependence is more evident in the case of low sliding velocity. Moreover, relaxation time constant of a dangling chain at the sliding interface scales with the same exponent as its stiffness. The scaling law is also developed for chain density and viscous retardation at the sliding interface. It is also established that the Hookean-based dynamic friction model is sufficient to study frictional behaviour of hydrogels. The reason for this observation is attributed to the weak bonding between a gelatin hydrogel and glass interface.

Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties

Gelatin‐based hydrogels offer various biochemical cues that support encapsulated cells and are therefore suitable as cell delivery vehicles in regenerative medicine. However, besides the biochemical signals, biomechanical cues are crucial to ensure an optimal support of encapsulated cells. Hence, we aimed to correlate the cellular response of encapsulated cells to macroscopic and microscopic elastic properties of glycidylmethacrylate (GMA)‐functionalized gelatin‐based hydrogels. To ensure that different observations in cellular behavior could be attributed to differences in elastic properties, an identical concentration as well as degree of functionalization of biopolymers was utilized to form covalently crosslinked hydrogels. Elastic properties were merely altered by varying the average gelatin‐chain length. Hydrogels exhibited an increased degree of swelling and a decreased bulk elastic modulus G′ with prolonged autoclaving of the starting solution. This was accompanied by an increase of hydrogel mesh size and thus by a reduction of crosslinking density. Tougher hydrogels retained the largest amount of cells; however, they also interfered with cell viability. Softer gels contained a lower cell density, but supported cell elongation and viability. Observed differences could be partially attributed to differences in bulk properties, as high crosslinking densities interfere with diffusion and cell spreading and thus can impede cell viability. Interestingly, a microscopic elastic modulus in the range of native soft tissue supported cell viability and elongation best while ensuring a good cell entrapment. In conclusion, gelatin‐based hydrogels providing a soft tissue‐like microenvironment represent adequate cell delivery vehicles for tissue engineering approaches. Copyright © 2016 John Wiley & Sons, Ltd.

Diffusion Behavior of Microbial Transglutaminase to Induce Protein Crosslinking in Oil-in-Water Emulsions

Food-grade hydrogel particles composed of sodium alginate were used to investigate the diffusion behavior of microbial transglutaminase (mTG) to induce crosslinking of interfacially adsorbed protein. For this purpose, mTG-loaded hydrogel beads were mixed with caseinate-stabilized oil-in-water emulsions, whereas Bradford assay and ammonia measurements were utilized to monitor the enzyme-induced interfacial protein crosslinking. Different alginate (0.5–1.5%) and gelling concentrations (50–500 mM CaCl2) were used to modulate the hydrogel mesh size and number of junction zones. The results indicated that mTG was able to diffuse out of alginate beads. However, a decrease in NH3 concentration with increasing alginate and CaCl2 levels was observed due to the formation of tight and dense bead structures. These results illustrate that the spatial distribution of molecules in complex matrices plays a key role on the enzyme accessibility

A revised correlation between molecular weight between crosslinks and equilibrium degree of swelling of hydrogel networks

Event Abstract Back to Event A revised correlation between molecular weight between crosslinks and equilibrium degree of swelling of hydrogel networks Dany J. Munoz-Pinto1 and Mariah S. Hahn2 1 Trinity University, Engineering Science, United States 2 Rensselaer Polytechnic Institute, Biomedical Engineering, United States Introduction: Among hydrogels properties, characterization of their capacity to transport solutes of different sizes is of great relevance for the biomedical community. Their diffusional capacity has been commonly estimated using the average molecular weight between crosslinks (Mc) which is calculated using equilibrium degree of swelling data[1]. However, the current correlation lacks of sensitivity and fails to accurately reflect the diffusional properties of more highly crosslink hydrogel networks[2]. To address this limitation, the present work first evaluated the robustness of the standard swelling correlation using poly(ethylene glycol) diacrylate (PEGDA) as a material model. The strength of the correlation was assessed by contrasting swelling and mechanical behavior as functions of hydrogel crosslink density (ρx).Second, an independent assessment of hydrogel mesh size (ξ) by molecular size exclusion (MSE) was utilized to calculate ρx. The resulting set of data followed more general trends for swelling and modulus. Finally, using the MSE data, an improved correlation between Mc and degree of swelling was generated. Material and Methods: Hydrogel Preparation. Hydrogels were prepared by the photopolymerization of aqueous solutions of 3.4, 6.0, 10.0 and 20.0 kDa PEGDA. For each PEGDA MW, six distinct polymer concentrations ranging from 8 to 30 wt% were characterized. Swelling Measures. The volumetric swelling ratios at the swollen and relaxed states (Q and Q’) were calculated from the hydrogel initial, swollen and dry weights. Mc and ρx for each hydrogel formulation were then determined using swelling data correlations[1]. Mesh Size Evaluation. Mesh size was independently estimated by molecular size exclusion experiments[3],[4]. The measured ξ was then used to back calculate Mc and ρx. Tensile Modulus (E) Evaluation. The modulus of each formulation was determined from the slope of the linear portion of the stress-strain curve using a ring test method and an Instron 3342 mechanical tester[5]. New Swelling Correlation Model. To generate a new model to correlate Mc and swelling data, the value 1/Mc from the MSE data and the effective number of chain per unit volume (Vc) from swelling data were fit to the linear model: 1/Mc=a+bVc'. Where Vc'=f(Q,Q')*Vc. Results and Discussion: As expected, Q and E of PEGDA hydrogels as functions of ρx exhibited a tradeoff behavior for both sets of data (Fig. 1A and 1B).However only the ρx estimates based on MSE-based mesh size measures (Fig. 1B) resulted in a general ρx-Q trend, which was independent of PEGDA MW. Furthermore, the data from MSE model was used to derive an improved correlation between Mc and degree of swelling of hydrogel networks (Fig. 1C). Conclusions: The current data shows that the values of 1/Mc can potentially be calculated from swelling data using a modified version of the current correlation. Although in this work we used PEGDA as a model, this correlation can potentially be extended to other polymer networks.

Long-Term Controlled Protein Release from Poly(Ethylene Glycol) Hydrogels by Modulating Mesh Size and Degradation.

Poly(ethylene glycol) (PEG)-based hydrogels are popular biomaterials for protein delivery to guide desirable cellular fates and tissue repair. However, long-term protein release from PEG-based hydrogels remains challenging. Here, we report a PEG-based hydrogel platform for long term protein release, which allows efficient loading of proteins via physical entrapment. Tuning hydrogel degradation led to increase in hydrogel mesh size and gradual release of protein over 60 days of with retained bioactivity. Importantly, this platform does not require the chemical modification of loaded proteins, and may serve as a versatile tool for long-term delivery of a wide range of proteins for drug-delivery and tissue-engineering applications.