Viscous Hydrogel Research Articles

Identification of hyaluronic acid in seized samples by Hypercarb chromatography-high resolution mass spectrometry.

Hyaluronic acid (HA) has been commonly used to treat osteoarthritis and joint injuries in horses and dogs since the 1970s. HA is a polysaccharide made up of alternating N-acetyl-d-glucosamine and d-glucuronic acid residues, with polymeric molecules achieving molecular weights as high as 20 MDa. High molecular weight HA forms a viscous hydrogel when dissolved in water, making HA solutions distinct from most other pharmaceutical preparations. Clear viscous solutions are often encountered during stable and kennel inspections, but in the absence of an analytical method, it is not possible to identify if these substances contain HA or other unknown compounds. This paper presents a simple method for the identification of HA in seized materials based on chemical hydrolysis followed by Hypercarb chromatography and MS/MS analysis.

Quantitatively measuring the cytotoxicity of viscous hydrogels with direct cell sampling in a micro scale format “MicroDrop” and its comparison to CCK8

Tissue engineering holds promise for developing therapeutic applications using viscous materials e.g. hydrogels. However, assessing the cytotoxicity of such materials with conventional assays can be challenging due to non-specific interactions. To address this, we optimized a live/dead staining method for quantitative evaluation and compared it with the conventional CCK8 assay. Our MicroDrop method involved seeding droplets containing 5000 cells in 10 µl medium on 12-well plates. After allowing them to adhere for 4 h, various viscous samples were applied to the cells and measurements were conducted using a fluorescence microscope immediately and at daily intervals up to 72 h. A sodium dodecyl sulfate (SDS) dilution series compared the MicroDrop with the CCK8 assay. The findings revealed a cell-type specific pattern for 10 mg/ml hyaluronic acid (HA), wherein MC3T3-E1 cells maintained 95% viability until 72 h, while L929 cells experienced a gradual decline to 17%. 2 mg/ml HA exhibited consistent viability above 90% across all time points and cell lines. Similarly, fibrin demonstrated 90% viability across dilutions and time points, except for undiluted samples showing a decrease from 85% to 20%. Gelatin-methacrylol sustained viability above 70% across all time points at both 5% and 10% concentrations. The comparison of the SDS dilution series between viability (MicroDrop) and metabolic activity (CCK8) assay showed a correlation coefficient of 0.95. The study validates the feasibility of the established assay, providing researchers with an efficient tool for assessing cytotoxicity in viscous materials. Additionally, it holds the potential to yield more precise data on well-known hydrogels.Graphical

Bio-Inspired Screwed Conduits from the Microfluidic Rope-Coiling Effect for Microvessels and Bronchioles

Tubular microfibers have recently attracted extensive interest for applications in tissue engineering. However, the fabrication of tubular fibers with intricate hierarchical structures remains a major challenge. Here, we present a novel one-step microfluidic spinning method to generate bio-inspired screwed conduits (BSCs). Based on the microfluidic rope-coiling effect, a viscous hydrogel precursor is first curved into a helix stream in the channel, and then consecutively packed as a hollow structured stream and gelated into a screwed conduit (SC) via ionic and covalent crosslinking. By taking advantage of the excellent fluid-controlling ability of microfluidics, various tubes with diverse structures are fabricated via simple control over fluid velocities and multiple microfluidic device designs. The perfusability and permeability results, as well as the encapsulation and culture of human umbilical vein endothelial cells (HUVECs), human pulmonary alveolar epithelial cells (HPAs), and myogenic cells (C2C12), demonstrate that these SCs have good perfusability and permeability and the ability to induce the formation of functional biostructures. These features support the uniqueness and potential applications of these BSCs as biomimetic blood vessels and bronchiole tissues in combination with tissue microstructures, with likely application possibilities in biomedical engineering.

Showcasing water-based delivery of an amino acid targeting fingermark developer in a hydrogel

Most recommended methods for visualising fingermarks on paper rely on chemical developers that target and react with amino acids. Traditionally, these developers are sprayed onto paper substrates in solutions of per- and polyfluoroalkyl substances (PFAS), but now those same PFAS chemicals are undergoing phaseout or phasedown, which threatens to undermine forensic capabilities. This situation provides an opportunity to pivot towards greener approaches to fingermark visualisation. The ideal methodology would be a water-based treatment, as these provide superior safety for practitioners, combined with environmental sustainability. A major hurdle to implementing a water-based fingermark developer targeting amino acids is that water, as a universal solvent, can dissolve the eccrine components in fingermarks, as well as any optical or luminescent dyes that are created, causing the ridge detail to run or dissolve. This work circumvents this problem by delivering the amino acid developer alloxan in a hydrogel, which enables sharp fingermark ridge details to be observed despite it being a water-based treatment. Alloxan dissolved in a viscous hydrogel is shown here to react with the amino acids in fingerprint residues to form the coloured dye murexide, supported by optimisation and characterisation studies.

Micromechanical Indentation Platform for Rapid Analysis of Viscoelastic Biomolecular Hydrogels.

The advent of biomedical applications of soft bioinspired materials has entailed an increasing demand for streamlined and expedient characterization methods meant for both research and quality control objectives. Here, a novel measurement system for the characterization of biological hydrogels with volumes as low as 75µL was developed. The system is based on an indentation platform equipped with micrometer drive actuators that allow the determination of both the fracture points and Young's moduli of relatively stiff polymers, including agarose, as well as the measurements of viscosity for exceptionally soft and viscous hydrogels, such as DNA hydrogels. The sensitivity of the method allows differentiation between DNA hydrogels produced by rolling circle amplification based on different template sequences and synthesis protocols. In addition, the polymerization kinetics of the hydrogels can be determined by time-resolved measurements, and the apparent viscosities of even more complex DNA-based nanocomposites can be measured. The platform presented here thus offers the possibility to characterize a broad variety of soft biomaterials in a targeted, fast, and cost-effective manner, holding promises for applications in fundamental materials science and ensuring reproducibility in the handling of complex materials.

Evaluation of cellular viability in chitosan/L-arginine hydrogels.

There is a lack of studies evaluating the toxicity of nitric oxide (NO) precursors in chitosan/L-arginine hydrogels and their topical administration. However, clarifying the characteristics of these elements is essential for their possible use in non-surgical techniques of tooth movement acceleration. Such characteristics include interaction with different cell types, metabolism and drug safety. This in vitro study aimed to assess the cytotoxicity of chitosan hydrogels on human HeLa cells using different concentrations of L-arginine. The hydrogels were synthesized in a materials engineering laboratory, with a controlled environment, using 4 different L-arginine concentrations of 0%, 10%, 15%, and 20%. Once the hydrogels were prepared, their physical and chemical properties were characterized, and viability analysis was performed using 2 different methods, including a 48-h assay with Artemia salina nauplii and a 24-h cell culture with human HeLa cells followed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assay. Data analysis was performed using a Mann-Whitney U test to evaluate positive and negative controls in the cell culture, with a significance level of 0.01. A Wilcoxon paired test contrasted the 24-h compared to 48-h Artemia salina assays, with a Kruskal-Wallis and post hoc Dunn test used to compare groups using a significance level of 0.05. In the more viscous hydrogels, Artemia salina nauplii decreased drastically in 24 h, while the 15% and 20% hydrogels had no statistical differences from the negative control. The 10% and 20% hydrogels were statistically different from the negative control when comparing cell culture data. Our findings suggest that chitosan/L-arginine hydrogels could be used in humans without toxic effects. However, more trials and tests are needed to evaluate tooth movement rate during orthodontic treatment.

Saltwater-Induced Rapid Gelation of Photoredox-Responsive Mucomimetic Hydrogels.

Shear-thinning hydrogels represent an important class of injectable soft materials that are often used in a wide range of biomedical applications. Creation of new shear-thinning materials often requires that factors such as viscosity, injection rate/force, and needle gauge be evaluated to achieve efficient delivery, while simultaneously protecting potentially sensitive cargo. Here, a new approach to establishing shear-thinning hydrogels is reported where a host-guest cross-linked network initially remains soluble in deionized water but is kinetically trapped as a viscous hydrogel once exposed to saltwater. The shear-thinning properties of the hydrogel is then "switched on" in response to heating or exposure to visible light. These hydrogels consist of polynorbornene-based bottlebrush copolymers with porphyrin- and oligoviologen-containing side chains that are cross-linked through the reversible formation of β-cyclodextrin-adamantane inclusion complexes. The resultant viscous hydrogels display broad adhesive properties across polar and nonpolar substrates, mimicking that of natural mucous and thus making it easier to distribute onto a wide range of surfaces. Additional control over the hydrogel's mechanical properties (storage/loss moduli) and performance (adhesion) is achieved post-injection using a low-energy (blue light) photoinduced electron-transfer process. This work envisions these injectable copolymers and multimodal hydrogels can serve as versatile next-generation biomaterials capable of light-based mechanical manipulation post-injection.

Effect of konjac glucomannan on gelling and digestive properties of myofibrillar protein in Litopenaeus vannamei based on molecular docking

Konjac glucomannan (KGM) is commonly used as a texture enhancer due to its distinctive gelling properties. This study aimed to investigate the changes in gelling and digestive properties of myofibrillar protein (MP) in Litopenaeus vannamei when modified with varying KGM (1/40, 1/20, and 1/10 of the MP weight, respectively). The physicochemical properties of KGM-modified MP including secondary and tertiary structures, emulsibility, particle size, and protein aggregation were significantly affected. In contrast, the KGM treatment group (1/20 of MP weight, MK20) exhibited the highest storage modulus, loss modulus, and thermal stability of MP. This resulted in an improvement in the water holding capacity, the stability of the three-dimensional space network, and the strength of the heat-induced MP gels. In addition, the digestion behavior of MP gel could be regulated by modifying MP with KGM. When compared to control sample, the digestion rate and hydrolysis degree of MK20 increased by 16.63% and 1.32 times, respectively. However, it should be noted that excessive KGM could result in the formation of a viscous hydrogel that permeates with MP, causing a loose degradation structure and reducing sensitivity to digestive enzymes. The molecular docking results indicated that KGM interacted with MP through hydrogen bonding, primarily relying on its hydroxyl group. This interaction disrupted the α-spiral structure of MP and promoted the expansion of its structure, and ultimately affected the physicochemical properties of MP and its heat-induced gel.

Branched fructo-oligosaccharides from Polygonatum Cyrtonema Hua as crosslinking agents for cellulose: A novel injectable and on-demand dissolution hydrogel for diabetic wound

Oligosaccharide-containing macromolecular bio adhesives are emerging as highly promising eco-friendly materials to enhance the cytocompatibility of viscous hydrogels for wound healing applications. In our prior research, we extensively elucidated the properties of branch-structure fructo-oligosaccharides derived from Polygonatum Cyrtonema Hua (referred to as PCOS). However, the characteristics of hydrogels based on fructo-oligosaccharides remain to be fully explored. In present work, we developed an injectable, PCOS/carboxymethyl cellulose (CMC) hydrogel which is a dual ion-physical cross-linked hydrogel that can be considered as a potential diabetic wound dressing. The tests showed that the optimal ratios for hydrogel preparation were 2 % CBM 940 (Carbomer 940), 5 % CMC and 10 % PCOS. The resultant hydrogel was formulated into composite hydrogels that were then used for the treatment of full-thickness excisional wounds in a db/db diabetic mouse model. Wound closure and histological evaluation confirmed its beneficial effect on wound healing. Further morphological analysis through scanning electron microscopy images revealed a porous hydrogel structure, while Fourier-transform infrared spectroscopy provided structural insights on the crosslinking reaction. Physicochemical properties of the hybrid hydrogels determined by rheological properties, thermogravimetric, water loss rate, et al., indicated that the double crosslinking PCOS/CMC hybrid hydrogel showed enhanced dynamic mechanical properties and water retention capacity compared to the CMC cellulose matrix hydrogels. Thus, this novel PCOS-hybrid hydrogel exhibited good dissolvability and injectable properties, which was proved to facilitate for the diabetic wound healing both in vitro and in vivo test and holds a potential clinical application in the wound healing.

Application of a Radiopaque Viscous Hydrogel Spacer for Prostate Cancer Radiation Therapy: A Prospective Phase 2 Study

The aim of this study was to evaluate the application of a radiopaque viscous spacer (RVS) for prostate cancer radiation therapy (RT), including injection procedure, toxicity, treatment planning, image guidance, and imaging results up to 12 months after RT. RVS (median, 10 mL) was injected between prostate and rectal wall in 30 patients. Cone beam computed tomography (CT) was performed during the course of RT, a magnetic resonance imaging 3 and 12 months after RT. Injection and treatment tolerability were analyzed. The resulting distribution was compared with a control group of 30 patients with an initially fluid spacer. Procedure- or device-related adverse events were not observed. Signs of hydrogel migration were not found in any case. The volume decreased by 25% at 3 months after RT, and small residues were detected at 12 months after RT in 3 cases (10%). The median rectal volume percentage within the 90% isodose was 3.0% (interquartile range, 1.5%-4.5%). Acute and late gastrointestinal toxicities were found in 17% and 3%, respectively (all grade 1). The median distance between prostate and rectum at the base/midplane/apex was greater for RVS in comparison to initially fluid spacer (14/12/11 mm vs 12/10/10 mm, respectively), the gel symmetry (right vs left from midline) was comparable. The application was assessed to be easier to control by the users, and visibility in cone beam CT as good. The injection of a radiopaque viscous hydrogel spacer resulted in a prostate-rectum distance of >10 mm in most cases. The resulting rectum volume within the high-dose region and RT toxicity were very low. Advantages in comparison to the conventional hydrogel spacer are predominantly an improved placement control during the injection process and good visibility on CT.

Application of a Radiopaque Viscous Hydrogel Spacer for Prostate Cancer Radiotherapy - A Prospective Multi-Institutional Phase II Study.

Rectal dose can be significantly decreased after spacer application. An initially fluid spacer (FS) spreads in a predetermined space, whereas the positioning of a viscous spacer is determined by needle guidance. The aim of this study was to evaluate the application a radiopaque viscous spacer (RVS) for prostate cancer radiotherapy (RT). In 30 patients including three centers, 10ml (median) of a RVS was injected between the prostate and anterior rectal wall. The resulting distance and distribution were determined in different planes and compared with a control group of 30 patients with a FS. A cone beam computed tomography (CBCT) was performed at least at the end of RT, a magnetic resonance imaging (MRI) 3 months and 12 months after RT. Injection and treatment tolerability were analyzed. With a median prostate volume of 40cm3, no overlap was found between planning target volume and rectal volume in most cases (median = 0cm3, interquartile range, IQR 0-0.6cm3). The median contoured RVS before, at the end and 3 months after RT was 8.5cm3, 8.7cm3 und 6.4cm3. Signs of hydrogel migration were not found in any case. Hydrogel visibility in CBCT was rated with "4" on a scale between 1 (poor) and 5 (excellent). Small residues were detected in the MRI 12 months after RT in 3 cases (10%). The median distance between prostate and rectum at the base / midplane / apex was 14mm / 12mm / 11mm. The median rectal volume percentage within the 90% and 80% isodoses was 3.0% (IQR 1.5-4.5%) bzw. 5.9% (IQR 3.0-10.6%). On a scale between 1 (difficult) and 5 (very easy), ease of application was rated with "3-4". Procedure- or device related adverse events have not been observed in any case. Acute and late gastrointestinal toxicities were found in 17% and 3%, respectively (all grade 1). The control of gel distribution of RVS relative to FS was rated with "3-5" on a scale between 1 (much worse) and 5 (much better), the ease of application relative to FS with "2-3" on a scale between 1 (much harder) and 5 (much easier). With a median contoured FS volume of 9.9cm3, the prostate-rectum distance at the base / midplane / apex was 12mm / 10mm / 10mm (significantly smaller in comparison to RVS). However, the lateral gel extension of RVS was smaller in all planes, statistically significant for all comparisons (base: 28mm vs. 34mm, midplane: 28mm vs. 32mm, apex: 21mm vs. 26mm). The gel symmetry (right vs. left) was comparable. The application of a radiopaque viscous hydrogel spacer is harder in comparison to the initially fluid spacer. However, it can be better controlled and is achievable without any complications. Visibility in CBCT is good. The resulting prostate-rectum distance is >10mm in most cases and slightly larger at the base in comparison to FS. The resulting rectum volume within the high dose region and radiotherapy toxicity are very low.

Surface tension-induced biomimetic assembly of cell-laden fibrous bundle construct for muscle tissue engineering.

The field of tissue engineering has been long seeking to develop functional muscle tissue that closely resembles natural muscle. This study used a bio-inspired assembly based on the surface tension mechanism to develop a novel method for engineering muscle tissue. This approach enabled uniaxially ordered electrospun fibers to naturally collide into an aligned bundle without the need for manual handling, thereby reducing cell damage during the cell culture procedure. During the assembly procedure, C2C12 myoblasts were cultured in a viscous collagen hydrogel that caused wetting while providing adequate structural stability for the cell-fiber construct. In addition, gene expression analysis of the resulting muscle-like fibril bundle revealed improved myogenic differentiation. These findings highlight the potential of using a collagen hydrogel and the surface tension mechanism to construct biologically relevant muscle tissue, offering a promising strategy that may outperform existing approaches. Overall, this study contributes to the development of advanced tissue engineering methods and brings us a step closer to creating functional muscle tissue for therapeutic and regenerative medicine applications.

(Invited) Unique Size-Dependent Electrochemistry of Metal Nanoparticles in Aqueous and Hydrogel Environments

Metal nanoparticles (NPs) exhibit unique size-dependent physical and chemical properties, providing many potential applications including sensing, catalysis, optoelectronics, medical diagnostics and disease therapeutics, among others. Here we describe interesting size-dependent metal oxidation, metal reduction, and electrocatalytic properties for Au and other metal nanoparticles that are coated with relatively weak-binding stabilizers, which is necessary for effective electron transfer at the metal NP surface. Metal oxidation potentials decrease dramatically negative with decreasing NP size, especially below 4 nm down to ~1 nm in radius. Electrocatalytic seeded-growth kinetics also depend strongly on the metal NP size (seed size). The thermodynamics of other oxidation/reduction reactions, such as galvanic replacement, also depend dramatically on metal NP size, resulting in unique alloy nanostructures with improved electrocatalytic reactivity and stability. Size-dependent electrophoretic deposition of metal nanoparticles to form thin films also results from size-dependent electrocatalytic properties, allowing metal NP separations based on electrocatalytic activity. These oxidation, reduction, galvanic replacement, and electrocatalytic properties change dramatically when the metal NPs are coated with strong ligand stabilizers or when placed in a viscous hydrogel environment. The effect of the ligand and environment will be described here. A better understanding of size-dependent reactivity of metal NPs as a function of the type of stabilizer and environment is important to realize their potential for tuning the properties to optimize them for a specific application.

Zero-waste preparation of supramolecular hydrogels and films comprising tannic acid and ultra-high-molecular-weight polyethylene oxide

Recently, tannic acid (TA) has been attracting attention as a component for supramolecular hydrogels. In fact, TA was reported to form viscous hydrogels with polyethylene oxide (PEO) (∼10 kDa), a typical macromolecule; however, little is known about hydrogels consisting of TA with ultra-high-molecular-weight (UHMW) PEO (≥100 kDa). In this study, TA/PEO hydrogels containing PEO of various molecular weights are prepared to investigate the effects of the molecular weight of PEO on the structure and characteristic physical properties of TA/PEO hydrogels. Interestingly, UHMW PEOs (≥100 kDa) formed stretchable hydrogel aggregates (TaPeO Gel), which were completely different from existing viscous TA/PEO gels (∼10 kDa). The mechanical properties of the TaPeO Gel (500 kDa) include high elongation, strong adhesive ability, and anti-swelling properties. In addition, the TaPeO Gel dried at 40 °C for 8 days was a lightweight and rigid material that exhibited shape memory and self-healing properties. Furthermore, a highly stretchable film (TaPeO Film) was obtained during the preparation of the TaPeO Gel by drying the unwanted supernatant from the TA/PEO mixture. These results suggest that advanced supramolecular gels and films can be prepared simultaneously from TA and UHMW PEO in a zero-waste process.

Xanthan biopolymer-based soil treatment effect on kaolinite clay fabric and structure using XRD analysis

In this study, we evaluated the impact of xanthan gum biopolymer (XG) on kaolinite fabrics using X-ray diffraction (XRD) and the ensuing changes in the compaction behavior and shear resistance of kaolinite soils. The XRD peak analysis revealed that XG changed kaolinite fabrics into face-to-face associations. Moreover, environmental scanning electron microscopy showed the formation of XG-bridges between kaolinite particles, resulting in the change in fabrics and subsequently improving the resistance of kaolinite to external forces. Consequently, as XG content increased, the maximum dry density decreased, and the undrained shear strength increased. The viscous XG hydrogels produced a higher optimal moisture content and increased resistance to shear force. This study showed that XG affects the mechanical properties of kaolinite through changing kaolinite fabrics (up to 0.5% of the XG-to-kaolinite mass ratio) and absorbing pore-fluids (excess XG over 0.5% of the XG-to-kaolinite mass ratio).

Rechargeable pore-filled composite hollow fiber membranes for water vapor separation

We propose a new method of using high-density polyethylene (HDPE) ultrafiltration hollow fibers, which are inexpensive but difficult to use as a dehumidification membrane. Dehumidification membranes have a wide range of applications and can also offer the benefit of water recovery. Conventional membranes for gas separation consist of a substrate and a thin layer that selectively permeates a desired gas. However, low-cost substrates such as HDPE are limited in their application due to the presence of large pores that prevent defect-free thin layer formation. To address the issue of large pores, we utilized hydrogels made from viscous solutions, that can be stably positioned in large pores. Specifically, we filled the pores of the HDPE substrate with hydrogels consisting of glycerin, polyvinyl alcohol (PVA), and glutaraldehyde (GA). The pore-filled membranes capable of separating water vapor were 40GPGM and 50GPGM, which were filled with 40GPM (40 wt% glycerin/1 wt% PVA/0.5 wt% GA) and 50GPG (50 wt% glycerin/1 wt% PVA/0.5 wt% GA), respectively. Since the pore-filled membranes were filled with viscous hydrogels, they could be washed and recharged. Accordingly, they showed good rechargeability when measuring properties during multiple pore-filling and washing processes. The water vapor permeance/selectivity/water flux of the pore-filled membranes were measured at various temperatures and feed flow rates. The water vapor permeance/selectivity/water flux of 40GPGM and 50GPGM measured at 35 °C and 3.5 L/min were 3400 GPU/110/0.12 kg/m2∙hr and 2398 GPU/469/0.14 kg/m2∙hr, respectively. After continuous operation for 30 days, it was confirmed that the pore-filled membranes had good long-term stability.

A Novel Amphotericin B Hydrogel Composed of Poly(Vinyl Alcohol)/Borate Complex for Ophthalmic Formulation.

In this study, we developed a water-soluble complex-hydrogel viscosity-controlled formulation of amphotericin B (AmB). AmB is insoluble in water, but borax makes it soluble by forming a complex with AmB. Borax also forms complexes with poly(vinyl alcohol) (PVA) to produce viscous hydrogels. Furthermore, boric acid interacts with mucin expressed in corneal epithelial cells. Accordingly, by utilizing these properties of borax simultaneously, we prepared a water-soluble AmB complex-hydrogel with poly(vinyl alcohol)/borate (PVA-B-AmB), which is suitable for eye drops. PVA-B-AmB was easily prepared by simply mixing aqueous AmB solution dissolved in borax, PVA solution, and water. The 11B-NMR results suggested that PVA-B-AmB existed by bonding PVA and AmB via boronic acid. PVA-B-AmB (gel ratio = 0.55) has a viscosity of 18.3 ± 0.5 mPa·s and is suitable for ophthalmic formulations. This formulation exhibited sustained release of AmB of approximately 45% at 24 h. It was also shown that this formulation interacts with mucin. These results suggest that PVA-B-AmB can be used as a water-soluble AmB preparation suitable for ophthalmic use.

Intratympanic Substance Distribution After Injection of Liquid and Thermosensitive Drug Carriers: An Endoscopic Study.

In the treatment of inner ear conditions, intratympanic injection emerges as an important drug delivery method. Novel compounds designed for intratympanic injection are routinely loaded in viscous drug carriers. To date, it is unclear if they can freely distribute in the middle ear. The aims of this study were to investigate the middle ear distribution of different drug carriers during intratympanic injection and to determine an optimal injection method for thermosensitive hydrogels. Twenty-one human temporal bones were intratympanically injected with fluid drug carriers or poloxamer-407 hydrogels at different tympanic membrane injection sites (inferior, anterior-superior) using different needle types (Whitacre, Quincke). Fluid distribution was evaluated via an endoscopic view. Injection volume, duration, backflow, and overall safety were analyzed. Liquid drug carriers distribute effortlessly in the middle ear, whereas an additional ventilation hole is advantageous when applying thermosensitive hydrogels. The round window is coated with required volumes between 150 and 200 μl, irrespective of the injection position. Required volumes to also coat the stapedial footplate ranged from 310 to 440 μl. Use of the Whitacre-type needle reduced backflow to the ear canal and enabled longer tympanic membrane visibility when no additional ventilation hole was placed. Intratympanic injection is a safe and reliable method for the application of thermosensitive hydrogels. The round window niche is readily filled regardless of the injected formulation and injection position. Although fluid drug carriers distribute effortlessly in the middle ear, the placement of an additional ventilation hole might facilitate the application of viscous hydrogels.

Paper-Based Distance Sensor for the Detection of Lipase via a Phase Separation-Induced Viscosity Change.

Human pancreatic lipase is a symbolic biomarker for the diagnosis of acute pancreatitis, which has profound significance for clinical detection and disease treatment. Herein, we first demonstrate a paper-based lipase sensor via a phase separation-induced viscosity change. Lipase catalyzes triolein to produce oleic acid and glycerol. Adding an excess of Ca2+ produces calcium oleate. The remaining Ca2+ binds with sodium alginate, triggering hydrogelation with an "egg-box" structure. The viscosity change of the aqueous solution induced by the phase separation process can be quantified by measuring the solution flow distance on a pH test paper. The paper-based lipase sensor has high sensitivity with a detection limit of 0.052 U/mL and also shows excellent specificity. Additionally, it is also utilized for quantitative lipase analysis in human serum samples to exhibit its potency in acute pancreatitis detection. This method overcomes the drawbacks of low sensitivity, slow response, and poor reproducibility caused by the nonuniform distribution of the highly viscous hydrogel on the sensing interface in existing approaches. In conclusion, thanks to the prominent characteristics of high portability, low cost, and easy operation, it is prospective for simple quantitative detection of lipase and has great potential for commercialization.

Self-assembly and Hydrogelation Properties of Peptides Derived from Peptic Cleavage of Aggregation-prone Regions of Ovalbumin.

Egg white protein hydrolysate generated with pepsin was investigated for the presence of peptides with self-assembly and hydrogelation properties. Incubation of the hydrolysates for 16 h resulted in aggregates with significantly (p < 0.05) lower free amino nitrogen and sulfhydryl contents, and higher particle diameter and surface hydrophobicity compared to the hydrolysates. LC-MS/MS analysis of the aggregates resulted in identification of 429 ovalbumin-derived peptides, among which the top-six aggregation-prone peptides IFYCPIAIM, NIFYCPIAIM, VLVNAIVFKGL, YCPIAIMSA, MMYQIGLF, and VYSFSLASRL were predicted using AGGRESCAN by analysis of the aggregation “Hot Spots”. NIFYCPIAIM had the highest thioflavin T fluorescence intensity, particle diameter (5611.3 nm), and polydispersity index (1.0) after 24 h, suggesting the formation of β-sheet structures with heterogeneous particle size distribution. Transmission electron microscopy of MMYQIGLF, and VYSFSLASRL demonstrated the most favorable peptide self-assembly, based on the formation of densely packed, intertwined fibrils. Rheological studies confirmed the viscoelastic and mechanical properties of the hydrogels, with IFYCPIAIM, NIFYCPIAIM, VLVNAIVFKGL, and VYSFSLASRL forming elastic solid hydrogels (tan δ < 1), while YCPIAIMSA and MMYQIGLF formed viscous liquid-like hydrogels (tan δ > 1). The results provide valuable insight into the influence of peptide sequence on hydrogelation and self-assembly progression, and prospects of food peptides in biomaterial applications.