Hydrogel Volume Research Articles

Ultrasensitive Surface-Enhanced Raman Scattering Platform for Protein Detection via Active Delivery to Nanogaps as a Hotspot.

Surface-enhanced Raman scattering (SERS) is an attractive technique in molecular detection with high sensitivity and label-free characteristics. However, its use in protein detection is limited by the large volume of proteins, hindering its approach to the narrow spaces of hotspots. In this study, we fabricated a Au nanoTriangle plate Array on Gel (AuTAG) as an SERS substrate by attaching a Au nanoTriangle plate (AuNT) arrangement on a thermoresponsive hydrogel surface. The AuTAG acts as an actively tunable plasmonic device, on which the interparticle distance is altered by controlling temperature via changes in hydrogel volume. Further, we designed a Gel Filter Trapping (GFT) method as an active protein delivery strategy based on the characteristics of hydrogels, which can absorb water and separate biopolymers through their three-dimensional (3D) polymer networks. On the AuTAGs, fabricated with AuNTs modified with charged surface ligands to prevent the nonspecific adsorption of analytes to particles, the GFT method helped the delivery of proteins to hotspot areas on the AuNT arrangement. This combination of a AuTAG substrate and the GFT method enables ultrahigh sensitivity for protein detection by SERS up to a single-molecule level as well as a wide quantification concentration range of 6 orders due to their geometric advantages.

Assessment of three-dimensional large-scale deformations during drying of hydrogels via a structure from motion photogrammetry

A low-cost, efficient and accurate structure from motion (SfM) photogrammetry is used to reconstruct the complex morphologies of unevenly deforming hydrogels during the drying process. The primary setups comprise a camera and rotary platform, which are low-cost and works stably for most drying conditions. The dynamic three-dimensional (3D) reconstruction of cylindrical hydrogel samples is achieved by SfM through the generation of point clouds, and the 3D morphologies are calculated by a Poisson reconstruction algorithm based on these point clouds. The accuracy of SfM in quantitatively measuring large-scale deformation is validated, and its applications in drying studies are explored. The results show that as drying proceeds, the maximum measurement deviation of the hydrogel volume between SfM and the traditional buoyancy force method is 1.93% at a volume shrinkage of 69%, confirming the accuracy of the current method for measuring large-scale drying shrinkage. Based on SfM, the temporal evolution of the cross section of the hydrogel is obtained. Comparing to conventional drying experiments that assess the dryness of deformed materials based on overall moisture content changes, SfM enables the evaluation of localized complete drying by quantitative analysis of deformation parameter variations.

EUS-guided hydrogel injection to separate pancreatic head carcinoma from duodenum for enhanced radiotherapy: Multi-site feasibility study.

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and the head of the pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration.

Smart Hydrogel Swelling State Detection Based on a Power-Transfer Transduction Principle.

Stimulus-responsive (smart) hydrogels are a promising sensing material for biomedical contexts due to their reversible swelling change in response to target analytes. The design of application-specific sensors that utilize this behavior requires the development of suitable transduction concepts. The presented study investigates a power-transfer-based readout approach that is sensitive to small volumetric changes of the smart hydrogel. The concept employs two thin film polyimide substrates with embedded conductive strip lines, which are shielded from each other except at the tip region, where the smart hydrogel is sandwiched in between. The hydrogel's volume change in response to a target analyte alters the distance and orientation of the thin films, affecting the amount of transferred power between the two transducer parts and, consequently, the measured sensor output voltage. With proper calibration, the output signal can be used to determine the swelling change of the hydrogel and, consequently, to quantify the stimulus. In proof-of-principle experiments with glucose- and pH-sensitive smart hydrogels, high sensitivity to small analyte concentration changes was found along with very good reproducibility and stability. The concept was tested with two exemplary hydrogels, but the transduction principle in general is independent of the specific hydrogel material, as long as it exhibits a stimulus-dependent volume change. The application vision of the presented research is to integrate in situ blood analyte monitoring capabilities into standard (micro)catheters. The developed sensor is designed to fit into a catheter without obstructing its normal use and, therefore, offers great potential for providing a universally applicable transducer platform for smart catheter-based sensing.

Photothermally responsive and durable polydopamine-modified MXene-PNIPAM hydrogels for smart friction regulation

In this study, a polydopamine (PDA)-modified MXene-PNIPAM (pMP) hydrogel is prepared using a soap-free emulsion polymerization method, which shows enhanced anti-oxidative, photo-thermal, and tribological properties. The introduction of PDA not only inhibits the oxidation of MXene but also enhances the photo-thermal conversion efficiency of the hydrogel. Even after 50 days, it can still maintain good photo-thermal conversion performance. Moreover, compared with PNIPAM hydrogel, the friction coefficient (COF) and wear volume of pMP hydrogel as lubricant were reduced by 33% and 85%, respectively. Interestingly, the control of COF with excellent reversibility and durability is achieved using pMP hydrogel modulated by near-infrared light. The pMP composite hydrogel exhibits promising prospects in the fields of intelligent robots and biomedical devices.

RSM optimized chitosan based composite hydrogel for sustained drug delivery applications

Hybrid hydrogels with good biocompatibility have practical applications in the field of drug delivery. However, it remains challenging to formulate the hybrid hydrogels for sustained drug release by regulating their pore size and degradation rates. Herein, a hybrid chitosan-alginate hydrogel (superabsorbent) was synthesized using maleic acid as a cross-linker and acrylamide as a grafting agent. The composite hydrogel exhibited a good swelling percentage of 1246% (at pH 10), analysed using response surface methodology (RSM). The hybrid hydrogel system was hemocompatible as well as biocompatible and utilized for drug delivery applications. Pantoprazole sodium was taken as a model drug and it was loaded in the superabsorbent using the swelling diffusion method. The composite hydrogel showed excellent encapsulation efficiency for pantoprazole sodium (99.74%). The intermolecular interactions between hydrogel and drug were examined using different analytical techniques including XRD (X-Ray Diffraction), FTIR (Fourier transform infrared), SEM (Scanning electron microscope), thermal analysis and EDX (Energy dispersive X-ray) mapping. The swelling percentage of the drug loaded hydrogel under simulated gastrointestinal conditions was recorded as 917.80% (at stomach pH 1.2) and 756.95% (at intestinal pH 7.4) where protonation/deprotonation of the drug in the hydrogel matrix played an important role. In vitro drug release from the drug-loaded hydrogel was sustained up to 10 days and correlated with its swelling tendency, displaying higher release profiles at pH 1.2 (99.69%) than at pH 7.4 (72.16%). The pore volume of hydrogel was tuned varying the cross-linker amount during synthesis. BET (Brunauer-Emmett-Teller) results revealed that the pore volume of the hydrogel varied between 0.01775–0.01327 cm3/g for the cross-linker amount between 0.18–0.26 g, respectively. The impact of various factors including amount of cross-linker, pore volume, and drug loading percentage on drug release at pH 1.2 and 7.4 was studied statistically as well as experimentally and these factors significantly controlled the drug release percentage. The drug release from the hydrogel followed the Makoid-Banakar model with Fickian diffusion mechanism. The synthesized composite chitosan-alginate hydrogel could be a promising candidate for its utilization as a sustained drug delivery system.

Chitosan based hybrid superabsorbent for controlled drug delivery application.

In the present study, a hybrid chitosan-alginate superabsorbent is prepared using maleic acid as a cross-linker and acrylamide as a grafting agent using the free radical mechanism. The composite hydrogel shows good swelling capacity along with hemocompatibility and biocompatibility and hence it is utilized as a drug delivery device. The characterization techniques including x-ray diffraction, Fourier transform infrared, x-ray photoelectron spectroscopy, and thermal analysis indicate the successful synthesis of stable hydrogel with rich functionalities. Metformin hydrochloride is used as a model drug which is used to treat diabetes. The drug encapsulation is done using the swelling diffusion method after the synthesis of hydrogel. The release of metformin from the drug-loaded hydrogel at physiological pH highlights the role of non-covalent interactions between the drug and hydrogel. In vitro release studies of Metformin from the drug-loaded hydrogel show higher release profiles at intestinal pH (7.4) compared to stomach pH (1.2). The observed cumulative release is 82.71% at pH 7.4 and 45.67% at pH 1.2 after 10 h. Brunauer-Emmett-Teller analysis reveals the effect of surface area, pore size, and pore volume of hydrogel on the drug release. The drug release from the hybrid chitosan-alginate hydrogel is found to be more sustained in comparison to the pure chitosan hydrogel. For the present drug delivery system, the swelling-controlled release is found to be more dominating than the pH-controlled release. The synthesized hydrogel can be successfully employed as a potential drug delivery system for controlled drug delivery.

Thermoresponsive injectable self-healing hydrogel containing polydopamine-coated Fe/Mo-doped TiO2 nanoparticles for efficient synergistic sonodynamic-chemodynamic-photothermal-chemo therapy

A smart hydrogel loading multifunctional nanoparticles and anticancer drugs was designed to achieve synergistic therapy against tumors with high efficiency and specificity. The thermoresponsive injectable self-healing hydrogel was prepared through the Schiff base between aldehyde-functionalized poly(2-(2-methoxyethoxy) ethyl methacrylate)–co-oligo(ethylene glycol) methacrylate-co-2-hydroxyethyl methacrylate) (P(MEO2MA-co-OEGMA-co-HEMA), APMOH) and hydroxypropyl chitosan (HPCS). The polydopamine-coated Fe/Mo-doped titanium dioxide nanoparticles (PDA@dTiO2 NPs) were prepared and dispersed into the hydrogel with anticancer drug doxorubicin (DOX). PDA@dTiO2 NPs as sonosensitizers can convert oxygen into singlet oxygen (1O2) under ultrasound (US) irradiation, achieving sonodynamic therapy (SDT). They were also considered nanoenzymes, generating oxygen to supply an oxygen source for SDT, producing hydroxyl radical (·OH) to achieve chemodynamic therapy (CDT), and eliminating glutathione (GSH) to enhance the level of oxidative stress. After near-infrared (NIR) irradiation, the temperature of the hydrogel increased due to the photothermal ability of the polydopamine (PDA) layer. When the temperature reached the hydrogel's lower critical solution temperature (LCST), the hydrophilic-hydrophobic transformation occurred, and the hydrogel volume contracted. Consequently, the release rate of PDA@dTiO2 NPs and DOX increased, improving the therapeutic effects. The nanocomposite hydrogel system can achieve synergistic sonodynamic-chemodynamic-photothermal-chemo therapy (SDT-CDT-PTT-CT) for tumors, providing a novel platform for synergistic tumor treatment.

Cryosectioning of Hydrogels as a Reliable Approach to Increase Yield and Further Tune Mechanical Properties.

Decellularized extracellular matrix (dECM) hydrogels have emerged as promising materials in tissue engineering. The steps to produce dECM hydrogels containing the bioactive epitopes found in the native matrix are often laborious, including the initial harvesting and decellularization of the animal organ. Furthermore, resulting hydrogels often exhibit weak mechanical properties that require the use of additional crosslinkers such as genipin to truly simulate the mechanical properties of the desired study tissue. In this work, we have developed a protocol to readily obtain tens of thin dECM hydrogel cryosections attached to a glass slide as support, to serve as scaffolds for two-dimensional (2D) or three-dimensional (3D) cell culture. Following extensive atomic force microscopy (AFM)-based mechanical characterization of dECM hydrogels crosslinked with increasing genipin concentrations (5 mM, 10 mM, and 20 mM), we provide detailed protocol recommendations for achieving dECM hydrogels of any biologically relevant stiffness. Given that our protocol requires hydrogel freezing, we also confirm that the approach taken can be further used to increase the mechanical properties of the scaffold in a controlled manner exhibiting twice the stiffness in highly crosslinked arrays. Finally, we explored the effect of ethanol-based short- and long-term sterilization on dECM hydrogels, showing that in some situations it may give rise to significant changes in hydrogel mechanical properties that need to be taken into account in experimental design. The hydrogel cryosections produced were shown to be biocompatible and support cell attachment and spreading for at least 72 h in culture. In brief, our proposed method may provide several advantages for tissue engineering: (1) easy availability and reduction in preparation time, (2) increase in the total hydrogel volume eventually used for experiments being able to obtain 15-22 slides from a 250 µL hydrogel) with a (3) reduction in scaffold variability (only a 17.5 ± 9.5% intraslide variability provided by the method), and (4) compatibility with live-cell imaging techniques or further cell characterization of cells.

Same-day versus delayed simulation imaging after placement of a perirectal hydrogel spacer for prostate radiotherapy.

Placement of a perirectal hydrogel spacer has been demonstrated to reduce the risk of rectal toxicity from prostate radiation. Practices vary regarding the timing of CT simulation after hydrogel placement, and the ideal schedule remains unknown. Thirty patients with localized prostate adenocarcinoma underwent transrectal ultrasound-guided placement of an iodinated SpaceOAR™ hydrogel prior to radiotherapy. Per evolving practice, 15 completed same-day simulation and 15 returned for simulation 1-2 weeks later. Hydrogel volume, perirectal distance, air-void volume, and rectal dosimetry per NRG GU005 were compared between CT simulation, 1st fraction Cone-Beam-CT (CBCT), and final CBCT. CT simulation occurred 8.8 ± 2.4 days after placement in the delayed group, with no significant difference in the interval between simulation and 1st fraction between groups (p = 0.165). Greater observed de-creases in hydrogel volume (0.57 cc vs. 0.04 cc, p = 0.0002), and perirectal distance at both mid-gland (1.32mm vs. 0.17mm) and tallest point (2.40mm vs. 0.04mm) were seen on 1st-fraction CBCT in the same-day group (p = 0.0039; p = 0.0002). Per dosimetry recalculated on 1st fraction CBCT, five (D3 cc and D50%) versus one (D50%) rectal dose parameters were exceeded in the same-day and delayed groups, respectively, and 10 versus one parameters had a relative increase of ≥ 20%. Due to the evolving anatomic changes in the days following hydrogel placement, same-day simulation scanning may introduce unintended variability in rectal dosimetry at the time of prostate radiotherapy.

Building a tissue: gingiva- and adipose-derived mesenchymal cell spheroids’ survivability and functionality after 3D extrusion bioprinting

While being the most extensively used cell type for spheroid-based 3D extrusion bioprinting, mesenchymal stromal cells (MSCs) provide a wide spectrum of biological properties depending on their origin. Understanding the specifics of each heterogeneous MSCs population subgroup would allow one to increase the survivability and functionality of the constructed tissue analogues. To answer this need, this study assessed the survivability, metabolic activity, proliferation, sprouting, migration, and differentiation capacity of MSCs spheroids depending on the cell source (adipose tissue, AT-MSCs/gingiva, G-MSCs) and on the tissue construct's geometry (bioprinted/manually mixed). This study has demonstrated that the cell origin defines the dynamics of spheroid reactivation, resulting in a varying construct's morphology after a 14-days-long cultivation period. AT-MSCs migrate in the hydrogel faster, forming clusters of wide and short sprouts. G-MSCs, oppositely, produce thin, long, and branched sprouts. Hence, AT-MSCs can quickly populate the hydrogel volume, achieving a high cell density, while G-MSCs can cover larger areas, but with a more sprout-like phenotype.

The thermal performance and mechanical stability of methacrylic acid porous hydrogels in an aqueous medium at different initial temperatures and hydrogel volume fraction using the molecular dynamics simulation

Hydrogels are insoluble and often in the form of a three-dimensional polymer network and can absorb body fluids in the biological environment. Such materials are created from hydrophilic monomers and sometimes from another type of monomers called hydrophobic monomers for use in special applications. Synthetic polymers are inherently hydrophobic and have better chemical stability than natural polymers. In this research, the TP (thermal properties) and MP (mechanical properties) of methacrylic acid porous hydrogels in an aqueous medium have been studied using molecular dynamics (MD) simulation. The results showed the hydrogel's thermal conductivity (TC) increased from 0.103 to 0.114 W/m.K by increasing the volume fraction (VF) from 5 to 15%. Also, Young’s modulus (YM) and ultimate strength (US) increased from 247 MPa and 131 to 274 MPa and 146 MPa, respectively. The TC of hydrogel increased from 0.103 to 0.116 W/m.K with increasing initial temperature (IT) from 300 to 350 K. The strength of the sample decreased from 131.78 to 115.97 MPa by increasing the IT to 350 K at a stress of 32%. It is expected that various medical and industrial applications will be improved by investigating and optimizing the investigated parameters in hydrogels.

Creatinine Imprinted Photonic Crystals Hydrogel Sensor

There is a demand for simple, selective, and efficient assays for the determination of clinically important metabolites such as creatinine for healthcare. Creatinine is the by-product of muscle energy metabolism and is excreted by the kidneys. To measure creatinine in the human serum, a creatinine imprinted photonic crystal hydrogel (CIPC hydrogel) for naked-eye detection is developed. CIPC hydrogel utilizes polystyrene-based two-dimensional (2D) photonic crystal colloidal arrays (PCs-array) embedded in the polyacrylamide hydrogel containing methacrylic acid which imprinted the creatinine template. The nanocavities in the hydrogel produced after the removal of the template bind to and recognize creatinine in the serum samples. The binding is selective and specific for creatinine. The binding is observed as shrinkage of the hydrogel volume and a decrease in the particle spacing which is monitored through changes in the Debye diffraction ring diameter and a visible blue-green to blue color shift. The binding event and the mechanism are investigated by molecular dockings. The CIPC sensor demonstrates a limit of detection (LOD) of 2.45 ± 1.6 µM, a linear detection range (25–500 µM), and recovery from 85.6 % to 99.9 % in the serum samples. CIPC hydrogel is available for the rapid and quantitative onsite detection of creatinine in the human serum sample.

In vitro исследование динамики элюции антибактериальных препаратов, импрегнированных в матрицы на основе полимерного гидрогеля

The objective was to explore the dynamics and duration of antibiotic elution in samples based on polymer hydrogel and PMMA. Material and methods The samples impregnated with vancomycin, rifampicin and cefazolin at various concentrations were placed in phosphate-buffered saline and incubated at 37 °C. The medium was completely replaced at 1, 3, 7, 14, 21 and 28 days. Spectrophotometry was used to measure concentration of drugs in solution and the release profiles. The median and 95 % CI were employed to statistically describe data obtained from 5 parallel studies. Results Concentrations of the antibiotics eluted from the polymer hydrogel were 7 times greater than those released from PMMA on day 1; 15 times greater on days 2 and 3; 6.6 times greater on day 7 and 3 times or more in the following days of observation. The rate of antibiotic release from hydrogel volumes also differed markedly. Discussion The drug release was more than 70% of the total amount for all hydrogel samples in contrast to PMMA with elution not exceeding 10 %. Despite the fact that a burst release was observed with 80 % of the antibiotic released in the first 5 days as seen in the case of bone cement, the concentration of the drug eluted from hydrogels was several times higher and exceeded the MIC throughout the observation period. The release of the antimicrobial agent from hydrogels was caused by diffusion of the particles from the entire volume of the matrix demonstrating an important advantage over PMMA with the potential being limited by surface depletion. Conclusion At this point, we have shown the possibility of creating potential depot systems based on unsaturated PVA derivatives with controlled release of antibiotics and characteristics being superior to PMMA.

Implantable and in-vivo shape-recoverable nanocellulose-hyaluronic acid composite hydrogel

Hydrogels have been used as a filling material in medical cosmetology, but current injection hydrogels have poor shaping ability due to its fluidity, while the hydrogels with fixed shape are easy to cause large wound size, resulting in rarely used in clinical practice. An implantable and in-vivo shape-recoverable hyaluronic acid (HA) based hydrogel is developed for tissue filling. In this work, complexes were made by hydrogen bonding between two natural polysaccharides: HA and TEMPO-oxidation cellulose nano-fiber. The elastic modulus of the HA/TOCN physical crosslinking hydrogel was maintained at 2500 G′ in Pa, while, when ethylene glycol diglycidyl ether was introduced in the hydrogel, the elastic modulus could reach 60,000 G′ in Pa. The volume of shrunk hydrogel reduced 80 ± 6 % of initial state, importantly, it can recover the shape in vivo inducing by extracellular moisture environment. Facts have proved that these shape recovery hydrogels were non-toxic to mammalian cells.

Rapid self-sealing of macro cracks of cementitious composites by in-situ alginate crosslinking

Despite the development of several self-healing concrete techniques, only micro cracks can be effectively self-repaired. To achieve self-healing of macro cracks (>1 mm), a strategy by in-situ calcium alginate crosslinking within cracks was proposed herein. This strategy was accomplished by encapsulating sodium alginate in polyethylene glycol granules coated with epoxy resin and calcium sulphoaluminate cement as protective shells. The capsules can release alginates and leach calcium in water once broken and subsequently the gelation can be conducted, thereby generating hydrogels. By incorporating the capsules in mortar specimens, hydrogels were successfully formed through calcium alginate crosslinking after cracking, which led to closures of 1–4 mm wide cracks and significant reduction of water permeability mainly in 1 day. The crack sealing due to crosslinking generation was further simulated by a modified model in terms of hydrogel volume growth and the predicted crack sealing evolutions were consistent with the experimental results.

Distributed pH sensing based on hydrogel coated single mode fibers and optical frequency domain reflectometry.

We propose a distributed pH sensor based on an optical frequency domain reflectometry using a PEGDA-based pH-sensitive hydrogel coated on a single mode fiber. The volume of hydrogel increased as pH value of the surrounding fluid decreased, which converts the pH value to the axial strain in the fiber. Taking capacity of distributed strain measurement with high spatial resolution in optical frequency domain reflectometry, the pH value of the external medium is distributed measured by the wavelength shifts of the local Rayleigh backscattering spectra. The basic hydrogel with different molecular weight was optimized to balance the sensitivity, the response time and also the stability. In the experiment, the range of the pH value from 2 to 6 was measured with a sampling resolution of 1.7 mm, a sensitivity of -199 pm/pH and a response time of 14 min when the hydrogel coating diameter is 2 mm. Such a distributed pH sensing system has a potential to detect and locate some chemical or biological substances in a large-scale environment.

Physics-Based Circuit Modeling of the Impedance Characteristics of a Smart Hydrogel-Actuated Bending Sensor.

Smart hydrogels are stimuli-responsive polymers which exhibit a volume-phase transition in response to external influences. This makes them promising candidates for sensing elements, especially in a biomedical context due to their easily achievable biocompatibility. The main challenge in harnessing the smart polymer's potential for sensor applications lies in a reliable transduction of the swelling change into an electrical signal. A novel platform approach is based on a bending sensor where the smart hydrogel acts as an actuator on a thin film with embedded metal traces. Mechanical deformation due to the hydrogel volume change alters the traces' electric impedance. However, besides deformation, the medium surrounding the sensor structure will also affect the impedance. For sensor design it is therefore crucial to understand the complex interdependencies between electric sensor properties, influences of the surrounding medium and mechanical deformation. Here, an electric circuit model is presented which considers all these contributions through a minimum number of lumped elements and is strictly based on physical considerations. By employing measured impedance spectra from an experimental sensor implementation subjected to different surrounding media and mechanical deformation, the validity of the simplified model is demonstrated. A detailed analysis and discussion give insights into the determination of the different model parameters and how external influences can clearly be attributed to specific circuit elements. This work provides a general approach for deducing minimalistic but strictly physics-based circuit models which can still adequately replicate the actual behavior of such types of impedance-based bending sensors.

Aptamer-functionalized 2D photonic crystal hydrogels for detection of adenosine.

Aptamer-functionalized two-dimensional photonic crystal (2DPC) hydrogels are reported for the detection of adenosine (AD). As a molecular recognition group, an AD-binding aptamer was covalently attached to 2DPC hydrogels. This aptamer selectively and sensitively binds AD, changing the conformation of the aptamer from a long single-stranded structure (AD-free conformation) to a short hairpin loop structure (AD-bound conformation). The AD-binding-induced changes of aptamer conformation reduced the volume of the 2DPC hydrogels and decreased the interparticle spacing of the 2DPC embedded in the hydrogel network. The particle spacing changes being dependent on AD concentration were determined by measuring 2DPC light diffraction using a simple laser pointer. The 2DPC hydrogel sensor showed a large particle spacing decrease of ~ 110nm in response to 1mM AD in phosphate-buffered saline (PBS). The linear range of determination of AD was 0.1nM to 1mM and the limit of detection was 0.09nM. The hydrogel sensor response for real samples was then validated in diluted fetal bovine serum (FBS) and human urine. The average % difference in particle spacing changes measured between diluted FBS and pure PBS was only 3.99%. In diluted human urine, the recoveries for the detection of AD were 95-101% and the relative standard deviations were 4.9-7.8%. The results demonstrate the potential applicability of the hydrogel sensor for real samples. This sensing concept, using the aptamer-functionalized 2DPC hydrogels, allows for a simple, sensitive, selective, and reversible detection of AD. It may enable sensor development for a wide variety of analytes by simply changing the aptamer recognition group.

Elastin-like Polypeptide Hydrogels for Tunable, Sustained Local Chemotherapy in Malignant Glioma.

Glioblastoma (GBM) is a primary brain tumor that carries a dismal prognosis, which is primarily attributed to tumor recurrence after surgery and resistance to chemotherapy. Since the tumor recurrence appears near the site of surgical resection, a concept of immediate and local application of chemotherapeutic after initial tumor removal could lead to improved treatment outcome. With the ultimate goal of developing a locally-applied, injectable drug delivery vehicle for GBM treatment, we created elastin-like polypeptide (ELP) hydrogels. The ELP hydrogels can be engineered to release anti-cancer drugs over an extended period. The purpose of this study was to evaluate the biomechanical properties of ELP hydrogels, to characterize their ability to release doxorubicin over time, and to investigate, in vitro, the anti-proliferative effect of Dox-laden ELP hydrogels on GBM. Here, we present microstructural differences, swelling ratio measurements, drug release characteristics, and in vitro effects of different ELP hydrogel compositions. We found that manipulation of the ELP–collagen ratio allows for tunable drug release, that the released drug is taken up by cells, and that incubation with a small volume of ELP-Dox hydrogel drastically reduced survival and proliferation of GBM cells in vitro. These results underscore the potential of ELP hydrogels as a local delivery strategy to improve prognosis for GBM patients after tumor resection.