Formation of pH-responsive hydrogel beads and their gel properties: Soybean protein nanofibers and sodium alginate.

Hydrogel beads prepared from protein nanofibers are popular because of their safety, sleek appearance, and protection of biologically active substances. However, extreme external environmental variations, such as pH and temperature, can limit their practical application. To meet the application requirements of hydrogel beads in different environments, non-covalent mixtures of CaCl2 cross-linked soybean protein nanofibers (SNF) and sodium alginate (SA) were used to prepare hydrogel beads. In the present study, the hardness (782.48 g) and elasticity of hydrogel beads formed at SNF/SA = 7:3 and CaCl2 concentration of 0.1 mol/L were the maximum. Furthermore, the water content and pH swelling also reached a peak (98.68 %, 43.85 g/g) due to the best morphology and regular internal network structure. Meanwhile, the pH-responsive hydrogel beads with added anthocyanins were able to respond to the ambient pH under different temperatures and pH conditions and maintained color stability during 96 h of storage (ΔE < 5). In this experiment, a pH-responsive hydrogel bead based on soybean protein nanofiber (SNF) and sodium alginate (SA) was prepared by simple ionic crosslinking. It provides a theoretical and experimental basis for the future application of plant protein nanofibers as pH-responsive hydrogel materials.

Widely distributable and retainable in-situ gelling material for treating myocardial infarction.

Intramyocardial hydrogel injection is a promising therapy to prevent negative remodeling following myocardial infarction (MI). In this study, we report a mechanism for in-situ gel formation without external stimulation, resulting in an injectable and tissue-retainable hydrogel for MI treatment, and investigate its therapeutic outcomes. A liquid-like polymeric solution comprising poly(3-acrylamidophenylboronic acid-co-acrylamide) (BAAm), polyvinyl alcohol (PVA), and sorbitol (S) increases the viscous modulus by reducing the pre-added sorbitol concentration is developed. This solution achieves a sol-gel transition in-vitro in heart tissue by spontaneously diffusing the sorbitol. After intramyocardial injection, the BAAm/PVA/S with lower initial viscous modulus widely spreads in the myocardium and gelate compared to a viscoelastic alginate (ALG) hydrogel and is retained longer than the BAAm/S solution. Serial echocardiogram analyses prove that injecting the BAAm/PVA/S into the hearts of subacute MI rats significantly increases the fraction shortening and ejection shortening and attenuates the expansion of systolic LV diameter for up to 21 d after injection compared to the saline injection as a control, but the ALG injection does not. In addition, histological evaluation shows that only the BAAm/PVA/S decreases the infarct size and increases the wall thickness 21 d after injection. The BAAm/PVA/S intramyocardial injection is better at restraining systolic ventricular dilatation and cardiac failure in the rat MI model than in the control groups. Our findings highlight an effective injectable hydrogel therapy for MI by optimizing injectability-dependent distribution and retention of injected material. STATEMENT OF SIGNIFICANCE: In-situ gelling material is a promising strategy for intramyocardial hydrogel injection therapy for myocardial infarction (MI). Since the sol-gel transition of reported materials is driven by external stimulation such as temperature, pH, or ultraviolet, their application in vivo remains challenging. In this study, we first reported a synthetic in-situ gelling material (BAAm/PVA/S) whose gelation is stimulated by spontaneously reducing pre-added sorbitol after contacting the heart tissue. The BAAm/PVA/S solution spreads evenly, and is retained for at least 21 d in the heart tissue. Our study demonstrated that intramyocardial injection of the BAAm/PVA/S with more extensive distribution and longer retention had better effects on preventing LV dilation and improving cardiac function after MI than that of viscoelastic ALG and saline solution. We expect that these findings provide fundamental information for the optimum design of injectable biomaterials for treating MI.

A Case of Migration of a Hydrogel Spacer for Radiotherapy into the Pulmonary Artery.

A 67-year-old man was referred to our hospital for the diagnosis and treatment of prostate cancer. Multidisciplinary discussion led to intensity-modulated radiotherapy preceded by hormone therapy. Before radiotherapy, a biodegradable hydrogel spacer (HS) was placed between the prostate and rectum to reduce radiation injury risk. Three weeks postplacement, pelvic magnetic resonance imaging revealed HS migration into the pelvic vein. Subsequent whole-body contrast-enhanced computed tomography (CECT) revealed HS migration into the pulmonary artery. The patient showed no symptoms or clinical signs. Radiotherapy was completed uneventfully. Complete absorption of the migrated HS was confirmed using CECT images 5 months postplacement.

Increasing rectum-prostate distance using a hydrogel spacer to reduce radiation exposure during proton beam therapy for prostate cancer.

SpaceOAR, a polyethylene-glycol hydrogel, reduces rectal radiation exposure during radiation therapy for prostate cancer. Previously, our group reported the modified technique of hydrogel insertion, which achieves greater separated distance at prostate-apex. This study aimed to investigate the impact of separated distance at prostate-apex and our modifier technique, on radiation exposure reduction during proton beam therapy (PBT). We included 330 patients undergoing PBT with the relative biological effectiveness (RBE) of 63 Gray (Gy) for localized prostate cancer, and categorized them into groups 0 (no spacer, n = 141), 1 (separated distance of spacer at the prostate-apex level < 7.5 mm, n = 81), and 2 (distance ≥ 7.5 mm, n = 108). The rectal volumes to receive 30-60 Gy (RBE), was estimated and described as Rectal V30-60 (ml) in 10 Gy increments. The Rectal V30-60 (ml) was significantly lower in group 2 than in group 1, and in group 1 than in group 0. After propensity score matching, the multivariate logistic regression analysis revealed that the most significant factor to reduce radiation exposure was our modified technique of hydrogel insertion. Therefore, using a hydrogel spacer to expand the prostate-rectum distance not only at prostate-mid to prostate-base level but also at the prostate-apex level can reduce the radiation exposure in PBT for prostate cancer.

SpaceOAR hydrogel distribution and early complications in patients undergoing radiation therapy for prostate cancer.

OBJECTIVES: Hydrogel spacers aim to separate the rectum from the prostate during radiation therapy for patients with prostate cancer to decrease the radiation dose and thus toxicity to the rectum. The aim of this study was to evaluate the distribution of the hydrogel spacer between the rectum and the prostate, to assess for hydrogel rectal wall infiltration and to assess for immediate complications. METHODS: Retrospective study of 160 patients who had undergone hydrogel spacer placement. Distribution of the hydrogel was assessed on MRI. MRI images were reviewed for rectal wall injection or other malplacement of gel. Early post-procedure complications were recorded. RESULTS: 117 (73.1%) patients had a symmetrical distribution of the hydrogel spacer. The mean anteroposterior rectoprostatic separation was 10.2 ± 3.7 mm (range 0-27 mm). Seven (4.3%) patient had minimal rectal wall infiltration and one (0.6%) patient had moderate infiltration. One (0.6%) patient had an intraprostatic injection of hydrogel. Two (1.3%) patients required treatment in the emergency department: one for urinary retention and one for pain. CONCLUSIONS: Transperineal hydrogel placement separates the prostate from the rectum with a symmetrical distribution in the majority of cases prior to radiation therapy with a low rate of rectal wall injection and immediate complications. ADVANCES IN KNOWLEDGE: SpaceOAR hydrogel can be safely injected into radiation naive patients with low- or intermediate-risk organ-confined prostate cancer. The spacer separates the prostate from the rectum with a symmetrical distribution in the majority of cases prior to radiation therapy.

Study of silicone hydrogel contact lenses' surface reflection characteristics using confocal microscopy.

The physical and chemical properties of contact lenses (CLs) differ significantly from one another. This is already covered by the FDA classification, which divides soft lenses into groups and subgroups for additional characteristics. The differences relate to both the interior and surface of the lens. Several differences in the surface characteristics of individual contact lenses have been studied and demonstrated to date. However, one of their fundamental physical properties, that is light reflection or, quantitatively, reflectance has not been compared. This paper describes the surface differences of a range of silicone-hydrogel (SiHy) lenses using reflectance confocal microscopy. It shows the relationship between the amount of light reflected from the lens surface and the material parameters. Common SiHy lens materials were used in the study, including two lenses with surface modifications. Light incident at the interface between two media (phosphate-buffered saline and lens) with different refractive indices is partially reflected. The normalized results show significant differences between the reflection signals (1 vs 0.07), and that they are not correlated with the refractive index (R2 = 0.5536). For the water content (%H2O), a general trend was observed that the higher the %H2O, the lower the reflection signal is (R2 = 0.8105). The reflection signal and surface modulus show the best correlation. (R2 = 0.9883). The proposed CLs analysis method, using reflectance confocal microscopy, provides data to differentiate between lenses with and without surface modifications.

Assessment of friction in aged soft contact lenses by an innovative method.

In the present research work, we intend to evaluate the effect of aging of CL (contact lenses) on friction and, in case there are alterations in the value of the coefficient of friction after aging, to understand which modifications in the material incite these variations. For this, a simulation of the aging process to which the CL are subject in vivo is carried out and the friction and stiffness of the CL are characterized, before and after aging. The aging procedure of SCLs (soft contact lenses) was simulated by a cycling process considering that the main parameter influencing the material surface is the transition between the closed and open eye and the exposure to environmental aggressions, particularly ultraviolet radiation. The values of the coefficient of friction and elastic modulus before and after the aging process were compared and was verified the increase of both parameters for all contact lenses. The hydrogel lens was the least affected by aging and the silicone - hydrogel lens based on delefilcon A was the one that showed the least stability of properties.

pH-sensitive gallol-rich chitosan hydrogel beads for on-off controlled drug delivery.

Malignant tumors have emerged as a serious health issue, and the interest in developing pH-sensitive polymers for site-specific drug delivery has increased. The physical and/or chemical properties of pH-sensitive polymers depend on the pH, and thus, drugs can be released by cleaving dynamic covalent and/or noncovalent bonds. In this study, gallic acid (GA) was conjugated to chitosan (CS) to prepare self-crosslinked hydrogel beads containing Schiff base (imine bond) crosslinks. The CS-GA hydrogel beads were formed by the dropwise addition of the CS-GA conjugate solution into a Tris-HCl buffer solution (TBS, pH 8.5). The pH-sensitivity of pristine CS was significantly enhanced following the introduction of GA moiety, and as a result, the CS-GA hydrogel beads swelled more than approximately 5000 % at pH 4.0, indicating an excellent swelling/deswelling ability of the beads at different pH (pH 4.0 and 8.5). The reversible breakage/recovery of the imine crosslinks in the CS-GA hydrogel beads was confirmed through X-ray photoelectron spectroscopic and rheological studies. Finally, Rhodamine B was loaded onto the hydrogel beads as a model drug to investigate the pH-sensitive drug release behavior. At pH 4, the drug was released up to approximately 83 % within 12 h. The findings indicate that the CS-GA hydrogel beads have great potential as a drug delivery system that is sensitive to acidic tumor sites in the body.

Physical Properties and Interaction With the Ocular Surface of Water-Gradient Contact Lenses.

ABSTRACT: Since the introduction of silicone hydrogel contact lenses, many silicone-hydrogel materials have been produced, including water-gradient contact lenses with a silicone hydrogel core and a thin hydrogel outer layer (e.g., delefilcon A, verofilcon A, and lehfilcon A). Their properties have been investigated in various studies assessing both the chemical-physical characteristics and the comfort, but the overall picture is not always consistent. In this study, water-gradient technology is reviewed by looking at basic physical properties both in vitro and in vivo and at the interaction with the human ocular surface. Surface and bulk dehydration, surface wetting and dewetting, shear stress, interaction with tear components and with other environmental compounds, and comfort are discussed.

Safety of hydrogel spacers for rectal wall protection in patients with prostate cancer: A retrospective analysis of 200 consecutive cases.

OBJECTIVE: To evaluate the safety and complications of hydrogel spacer implantation. METHODS: This single-center historical cohort study retrospectively analyzed cases of hydrogel spacer implantation between October 2018 and March 2022. The survey items were the rates of possible hydrogel injection implementation, the success rate of hydrogel implantation including asymmetry, higher position, rectal wall infiltration, subcapsular injection, and other adverse events, and width created by the spacer. To investigate the learning curve, 1, 2, and 3 points were assigned to adverse event grades G1, G2, and G3, respectively. Spacer effectiveness obstruction, such as asymmetry was assigned 3 points. A Mann-Whitney U test was performed to assess statistically significant differences. RESULTS: The study included a total of 200 patients with a median (range) age of 70 (44-85) years. In 10 (5%) patients, hydrogel injection implementation was not possible. Of 190 patients who underwent hydrogel spacer placement, 168 (88%) received a satisfactory placement. The median (range) width of hydrogel spacers was 13.1 (4.4-18.7) mm. Spacer asymmetry, higher position, rectal wall infiltration, and prostate subcapsular infiltration occurred in 7 (3.7%), 5 (2.6%), 12 (6.3%), and 1 (0.5%) patients, respectively. G1 and G3 adverse events occurred in 13 (7%) and 4 (2%) patients, respectively. Practitioner #1 who performed the highest number of procedures had significantly (p = 0.04) lower total scores in group B. CONCLUSION: Spacer implantation yielded favorable outcomes with a high percentage of appropriate spacer implantation, and few major complications.

Improvement of Soft Contact Lens Wettability After the Instillation of Hyaluronic Acid Eye Drops.

PURPOSE: To evaluate the effect of the topical instillation of hyaluronic acid eye drops with different viscosity on soft contact lens wettability and comfort. METHODS: A randomized and participant-masked study was performed, involving 20 participants (25.4±2.6 years). One eye wore hydrogel (ocufilcon D) contact lenses, and another eye wore silicone-hydrogel (somofilcon A) contact lenses. The in vivo wettability tear film surface quality (TFSQ) index and comfort were measured before and after the instillation of different eye drops: saline solution (control) and 0.1%, 0.2%, and 0.3% hyaluronic acid. RESULTS: Compared with saline solution, the instillation of 0.1%, 0.2%, and 0.3% hyaluronic acid improved the in vivo wettability of the hydrogel contact lenses by decreasing their TFSQ mean for 5, 10, and 30 min, respectively ( P <0.05). During silicone-hydrogel contact lens wear, the hyaluronic acid did not affect wettability because there were no changes in TFSQ mean ( P ≥0.05), but the 0.3% hyaluronic acid produced a decrease in comfort for the first 3 min ( P <0.05). CONCLUSIONS: The instillation of hyaluronic acid eye drops increased the in vivo wettability of the hydrogel contact lens, and the duration of this effect was directly related to its concentration and viscosity.

Silicone hydrogel contact lenses retain and document ocular surface lipid mediator profiles.

CLINICAL RELEVANCE: A leading reason for patients to abandon their contact lenses is discomfort. Mechanisms and biomarkers for lens discomfort remain to be elucidated. BACKGROUND: Physical stress and tear film interaction are likely factors for lens discomfort. Lipid mediators are generated from polyunsaturated fatty acids. They regulate ocular surface physiology and pathophysiology, are constituents of human tears and may interact with contact lenses. This study set out to determine if hydrogel lenses and silicone hydrogel lenses interact with tear film polyunsaturated fatty acids and polyunsaturated fatty acids-derived mediators. METHODS: In vitro incubations, rat experiments and analysis of worn human lenses assessed polyunsaturated fatty acids and lipid mediator interactions with lenses. Silicone hydrogel and hydrogel lenses were incubated with lipid mediators and polyunsaturated fatty acids up to 24 hours. Rats were fitted with custom silicone hydrogel lenses and basal tears collected. Silicone hydrogel lenses worn for 2 weeks were obtained from 57 human subjects. Tear and lens lipidomes were quantified by mass spectrometry. RESULTS: Silicone hydrogel lenses retained polyunsaturated fatty acids and lipid mediators within 15 minutes in vitro. Lenses contained 90% of total polyunsaturated fatty acids and 83-89% of total monohydroxy fatty acids by 12 hours. Retention correlated with polarity of lipid mediators and lipophilic properties of silicone hydrogel lenses. Polyunsaturated fatty acids and lipid mediators such as lipoxygenase- and cyclooxygenase-derived eicosanoids were present in tears and worn lenses from rats. Worn silicone hydrogel lenses from human subjects established robust and lens-type specific lipidomes with high levels of polyunsaturated fatty acids, lipoxygenase-pathway markers and subject-specific differences in lipoxin A4 and leukotriene B4. CONCLUSION: Worn silicone hydrogel lenses rapidly retain and accumulate tear polyunsaturated fatty acids and lipid mediators. Marked subject and lens type differences in the lipidome may document changes in ocular surface physiology, cell activation or infection that are associated with lens wear. If contact lens discomfort and adverse events induce specific tear and lens fatty acid and lipid mediator profiles warrants further studies.

An Intrapericardial Injectable Hydrogel Patch for Mechanical-Electrical Coupling with Infarcted Myocardium.

Although hydrogel-based patches have shown promising therapeutic efficacy in myocardial infarction (MI), synergistic mechanical, electrical, and biological cues are required to restore cardiac electrical conduction and diastolic-systolic function. Here, an injectable mechanical-electrical coupling hydrogel patch (MEHP) is developed via dynamic covalent/noncovalent cross-linking, appropriate for cell encapsulation and minimally invasive implantation into the pericardial cavity. Pericardial fixation and hydrogel self-adhesiveness properties enable the MEHP to highly compliant interfacial coupling with cyclically deformed myocardium. The self-adaptive MEHP inhibits ventricular dilation while assisting cardiac pulsatile function. The MEHP with the electrical conductivity and sensitivity to match myocardial tissue improves electrical connectivity between healthy and infarcted areas and increases electrical conduction velocity and synchronization. Overall, the MEHP combined with cell therapy effectively prevents ventricular fibrosis and remodeling, promotes neovascularization, and restores electrical propagation and synchronized pulsation, facilitating the clinical translation of cardiac tissue engineering.

Replica-mold nanopatterned PHEMA hydrogel surfaces for ophthalmic applications.

Biomimicking native tissues and organs require the development of advanced hydrogels. The patterning of hydrogel surfaces may enhance the cellular functionality and therapeutic efficacy of implants. For example, nanopatterning of the intraocular lens (IOL) surface can suppress the upregulation of cytoskeleton proteins (actin and actinin) within the cells in contact with the IOL surface and, hence, prevent secondary cataracts causing blurry or opaque vision. Here we introduce a fast and efficient method for fabricating arrays consisting of millions of individual nanostructures on the hydrogel surface. In particular, we have prepared the randomly distributed nanopillars on poly(2-hydroxyethyl methacrylate) hydrogel using replica molding and show that the number, shape, and arrangement of nanostructures are fully adjustable. Characterization by atomic force microscopy revealed that all nanopillars were of similar shape, narrow size distribution, and without significant defects. In imprint lithography, choosing the appropriate hydrogel composition is critical. As hydrogels with imprinted nanostructures mimic the natural cell environment, they can find applications in fundamental cell biology research, e.g., they can tune cell attachment and inhibit or promote cell clustering by a specific arrangement of protrusive nanostructures on the hydrogel surface.

Multipurpose Lens Care Systems and Silicone Hydrogel Contact Lens Wettability: A Systematic Review.

PURPOSE: To provide a relationship between materials developed for silicone hydrogel contact lenses and multipurpose care solutions to identify improvements in wettability, for prelens noninvasive break-up time and subjective score. METHODS: This systematic review was completed according to the updated PRISMA 2020 statement recommendations and followed the explanation and elaboration guidelines. The PubMed, Web of Science, and Scopus scientific literature databases were searched from January 2000 to November 2021. RESULTS: A total of four clinical trials published between 2011 and 2017 were included in this investigation. All included studies were randomized clinical trials. The success of contact lenses is related to the comfort of their use and therefore to the stability of the tear film and the wettability of its surface. The relationship between these parameters and changes in the ocular surface and inflammatory and infectious processes has been demonstrated. CONCLUSION: Hyaluronan and propylene glycol multipurpose solution (MPS) wetting agents achieved slightly higher prelens noninvasive break-up times than poloxamine. Polyquaternium-1 achieved better wettability and patient comfort than polyhexamethylene biguanide in medium-term studies. Short-term studies did not demonstrate differences between MPSs in their effect on contact lens wettability.

Electrodeposition induced covalent cross-linking of chitosan for electrofabrication of hydrogel contact lenses.

To meet the requirement of personalization, there is an urgent need to develop a simple, efficient and versatile manufacturing method for customized contact lens manufabrication. Here, we report a novel electrofabrication methodology (i.e., electrodeposition) for the fabrication of hydrogel contact lenses, which can induce covalent cross-linking between chitosan and epichlorohydrin simultaneously. The transmittance and toughness of hydrogels are improved by electrochemical cross-linking without affecting their oxygen permeability. Furthermore, the geometry of the chitosan based hydrogel contact lenses can be customized simply by the electrode template, and its characteristics can be regulated by electrical signals and electrochemical cross-linking. The electrodeposited hydrogel contact lenses have good optical properties, mechanical properties and biocompatibility, and their anti-adhesion properties to Staphylococcus aureus are close to commercial contact lenses. This work reveals the mechanism of electrochemical cross-linking between chitosan and epichlorohydrin and provides an alternative method for contact lens fabrication.

Controlled release of naringenin from soft hydrogel contact lens: An investigation into lens critical properties and in vitro release.

The naringenin (NAR)-impregnated hydrogel lenses (nesofilcon A material) were manufactured in this study with the feasibility to achieve controlled daily drug release. The lenses were fabricated using a comparable commercial-standard process, utilizing injection molding and thermal curing approaches. NAR-loaded lenses were prepared by both direct entrapment and 'soak and release' methods. Their critical properties were tested to ISO standards and comparable to the commercial lenses. NAR was fully characterized by studying its physical and chemical stability throughout the manufacturing processes using thermal analysis, high performance liquid chromatography and X-ray diffraction analysis. The NAR-loaded lenses showed > 97% light transmission, >75% water content, 0.50-0.53 ± 0.06 MPa tensile strength, with a lens diameter of 14.1 ± 0.1 mm. Lens polymerization kinetics were studied using differential scanning calorimetry. NAR released from the lens, prepared by a direct entrapment approach, followed a diffusion-controlled mechanism, and provided a controlled drug release of 72-82% for 24 h. A faster release rate was observed for NAR-loaded lenses prepared by a soak and release method, with over 90% of NAR was releasedin the first five hours.

Orbital and Sinonasal Complications of Hydrogel Scleral Buckle: A Case Report.

The hydrogel scleral buckle is a hydrophilic implant that is characterized by progressive expansion and can present with secondary orbital changes. The authors present a unique case of hydrogel-induced erosion of the orbital roof into the frontal sinus, with formation of a sino-orbital communication that resulted in frontal sinusitis and adjacent cerebritis. The hydrogel material is radiologically characterized as a fluid-filled hypertense T2 mass with rim enhancement and peripheral calcification. Awareness of late orbital complications from the hydrogel material is important to distinguish this entity from other mimicking orbital pathologies.