Transparent Hydrogel Research Articles

A versatile high-throughput assay based on 3D ring-shaped cardiac tissues generated from human induced pluripotent stem cell-derived cardiomyocytes

We developed a 96-well plate assay which allows fast, reproducible, and high-throughput generation of 3D cardiac rings around a deformable optically transparent hydrogel (polyethylene glycol [PEG]) pillar of known stiffness. Human induced pluripotent stem cell-derived cardiomyocytes, mixed with normal human adult dermal fibroblasts in an optimized 3:1 ratio, self-organized to form ring-shaped cardiac constructs. Immunostaining showed that the fibroblasts form a basal layer in contact with the glass, stabilizing the muscular fiber above. Tissues started contracting around the pillar at D1 and their fractional shortening increased until D7, reaching a plateau at 25±1%, that was maintained up to 14 days. The average stress, calculated from the compaction of the central pillar during contractions, was 1.4±0.4 mN/mm2. The cardiac constructs recapitulated expected inotropic responses to calcium and various drugs (isoproterenol, verapamil) as well as the arrhythmogenic effects of dofetilide. This versatile high-throughput assay allows multiple in situ mechanical and structural readouts.

A versatile high-throughput assay based on 3D ring-shaped cardiac tissues generated from human induced pluripotent stem cell-derived cardiomyocytes.

We developed a 96-well plate assay which allows fast, reproducible, and high-throughput generation of 3D cardiac rings around a deformable optically transparent hydrogel (polyethylene glycol [PEG]) pillar of known stiffness. Human induced pluripotent stem cell-derived cardiomyocytes, mixed with normal human adult dermal fibroblasts in an optimized 3:1 ratio, self-organized to form ring-shaped cardiac constructs. Immunostaining showed that the fibroblasts form a basal layer in contact with the glass, stabilizing the muscular fiber above. Tissues started contracting around the pillar at D1 and their fractional shortening increased until D7, reaching a plateau at 25±1%, that was maintained up to 14 days. The average stress, calculated from the compaction of the central pillar during contractions, was 1.4±0.4 mN/mm2. The cardiac constructs recapitulated expected inotropic responses to calcium and various drugs (isoproterenol, verapamil) as well as the arrhythmogenic effects of dofetilide. This versatile high-throughput assay allows multiple in situ mechanical and structural readouts.

Amorphous Tungsten Oxide Nanodots for Chromatic Applications

AbstractAmorphous tungsten oxide (WO3) is widely exploited in the fields of photochromism and electrochromism. Despite its widespread use, the tractable synthesis of amorphous WO3 nanodots is still on the drawing board, even though the WO3 nanodots possess superior chromatic performance owing to their large surface‐to‐volume ratio. Therefore, a new efficient strategy to synthesize amorphous WO3 nanodots, which exhibit both excellent electrochromic and photochromic properties, is reported. For the first time, the ligand effects of the amorphous WO3 nanodots on chromatic applications are elucidated. The presence of the ligand on amorphous WO3 nanodots inhibits the electrochromic color switching, while promoting photochromic performance. As a proof of concept, zinc‐WO3 electrochromic devices, WO3‐polyvinyl alcohol (PVA) transparent hydrogels, and PVA/WO3 textiles are prepared for diverse rapid‐switching chromatic applications. These results present a new strategy for the synthesis of widely used amorphous WO3 nanodots and open new opportunities for the development of WO3‐based chromatic applications.

High‐Adhesion, Weather Resistance, Reusable PAM/Gly/Gel/TA/Fe3+ Biopolymer Dual‐Network Conductive Hydrogel for Flexible Bioelectrode

AbstractConductive hydrogel is considered a promising wearable sensor material. Developing flexible conductive hydrogel sensors with stretchability, adhesion, and stability remains challenging. In this study, a transparent, self‐adhesive, antifreeze, anti‐UV, stretchable, conductive, and reusable hydrogel with polyacrylamide/glycerol/gelatin/tannic acid/Fe3+ (PGGT‐Fe3+) structure is successfully constructed through a simple one‐pot polymerization method. The PGGT‐Fe3+ hydrogel is composed of dual networks of polyacrylamide and gelatin for organic cross‐linking, using water/glycerol as the dispersion medium, and incorporates a viscous substance: tannic acid, and a conductive substance: metal ions (Fe3+). Due to the introduction of the abundant amino, carboxylic acid, and hydroxyl functional groups on gelatin and tannic acid, the PGGT‐Fe3+ hydrogel exhibits excellent and repeatable adhesion capabilities on various surfaces (including glass, metal, plastic, and pigskin) with maximum adhesion strength of 98 kPa when attached to pigskin. Furthermore, based on the stable conductive network and high conductivity, the hydrogel not only exhibits strain sensitivity, fast response, and stability but also can stably collect epidermal bio signals. In conclusion, this work provides a new approach to the design and development of next‐generation multifunctional conductive hydrogels and opens up vast possibilities for their applications in the flexible electronics field.

Transparent injectable sericin-honey hydrogel with antioxidant and antibacterial activities combined with feeding sericin accelerates diabetic wound healing.

Wound healing in diabetics is often impaired or delayed due to the presence of high reactive oxygen species and low antioxidant levels. Here, a sericin-honey semi-interpenetrating network hydrogel with excellent antioxidant activity was prepared. Besides, the sericin-honey hydrogel is transparent, injectable, sticky, highly porous, and has good swelling properties, antibacterial activity, and cell compatibility. Based on its good performance in vitro, sericin-honey hydrogel achieved effective in vivo treatment on a mouse diabetic wound model, significantly accelerating the wound healing process. Furthermore, the combined effect of feeding sericin solution played a positive role in strengthening the effect of diabetic wound repair.

Antibacterial Micelles-Loaded Carboxymethyl Chitosan/Oxidized Konjac Glucomannan Composite Hydrogels for Enhanced Wound Repairing.

Antibacterial hydrogels have emerged as a promising approach for effective wound treatment. However, despite extensive research on the fabrication of antibacterial hydrogels, it remains challenging to develop injectable, biocompatible, transparent, and mass-producible hydrogels with antibacterial properties. In this study, we successfully fabricated an antibacterial drug-loaded composite hydrogel, named CC45/OKG40/HS, through a Schiff base reaction between carboxymethyl chitosan (CC) and oxidized konjac glucomannan (OKG), followed by the encapsulation of stevioside-stabilized honokiol (HS) micelles. The CC45/OKG40/HS hydrogel exhibited several favorable properties, including a short gel time (<10 min), high water content (>92%), injectability, good adhesiveness, self-healing ability, and high transparency. In vitro experiments confirmed its excellent antibacterial properties, antioxidant activities, and high biocompatibility (no cytotoxicity, hemolysis ratio <5%). Furthermore, in vivo evaluation demonstrated that the CC45/OKG40/HS0.5 hydrogel accelerated wound healing by relieving inflammatory responses and enhancing re-epithelization. Given its feasibility for mass production, the findings showed that the CC45/OKG40/HS hydrogel has the potential as an advanced antibacterial wound dressing for commercial use.

A Multifunctional, Tough, Stretchable, and Transparent Curcumin Hydrogel with Potent Antimicrobial, Antioxidative, Anti-inflammatory, and Angiogenesis Capabilities for Diabetic Wound Healing.

The treatment of diabetic chronic wounds is still faced with great challenges, mainly due to wound infection, excessive inflammation, and peripheral vascular disease in the wound area. Therefore, it is of great importance to develop a novel multifunctional hydrogel with high efficiency to accelerate diabetic wound healing. Curcumin (Cur), a Chinese herbal, has shown great potential in enhancing the healing of diabetic chronic wounds because of its immunomodulatory and pro-angiogenic properties. However, its low aqueous solubility, poor bioavailability, and chemical instability have limited its clinical applications. To address these current bottlenecks, novel poly(vinyl alcohol) (PVA)-chitosan (CS)/sodium alginate (SA)-Cur (PCSA) hydrogels were prepared for the first time, and they demonstrated all of the above intriguing performances by the Michael addition reaction of CS and Cur. PCSA hydrogels show multiple dynamic bonds, which possess strong mechanical properties (tensile stress: ∼0.980 MPa; toughness: ∼258.45 kJ/m3; and compressive strength: ∼7.38 MPa at strain of 80%). These intriguing performances provided an optimal microenvironment for cell migration and proliferation and also promoted the growth of blood vessels, leading to early angiogenesis. Importantly, the experimental results demonstrated that PCSA hydrogels can effectively transform pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages without the need for additional ingredients in vitro. Benefiting from these characteristics, a full-thickness diabetic wound in a rat model demonstrated that PCSA hydrogels can effectively accelerate wound healing via ROS-scavenging, downregulation of IL-1β, and upregulation of CD31 expression, resulting in angiogenesis and collagen deposition. This strategy not only provides a simple and safe Cur-based hydrogel for diabetic wound healing but also highlights the significant potential for the development of high-performance biomaterials for promoting diabetic wound healing using traditional Chinese medicine.

Experimental Study on Rapid Hemostasis Using Peptide Hydrogels.

Uncontrolled hemorrhaging resulting from trauma, surgery, and disease-associated or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Self-assembling peptide nanofibers are particularly attractive due to their rapid and efficient hemostasis, biocompatibility, and wound-healing properties. In this study, we designed two types of 12-residue peptides by using a strong fishnet-like peptide sequence and a pro-cell adhesion sequence (Arg-Gly-Asp, RGD). The peptides are HN2-X-Ser-Phe-Cys-Phe-Lys-Phe-Glu-X-Arg-Gly-Asp-OH (where X is Pro or Tyr), which dissolve in deionized (DI) water and form stable and transparent functional hydrogels. Transmission electron microscopy and scanning electron microscopy demonstrated that the two peptides self-assemble into nanowebs and nanofibers, forming a fishnet-like and three-dimensional network structure. Circular dichroism and Fourier transform infrared spectroscopy analysis demonstrated that the self-assembled peptides mainly adopt a β-sheet structure with β-turn and α-helix as auxiliary assembly growth. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and SEM analysis showed that the cell survival rates were very good, delivering an obvious promotion of cell proliferation of fibroblasts and hepatocytes. Importantly, in vivo hemostasis delivered that the self-assembled peptide nanowebs and nanofibers had a good hemostatic effect on rat saphenous vein and liver bleeding, achieving 38 s faster hemostasis, which was better than commercial "Instantaneous" hemostatic powder. Accoupling the fast hemostasis and effective promotion of liver defect rapid repair, the peptide self-assembly strategy offers a clinically promising treatment option for life-threatening liver bleeding and serves as a renewed impetus for the development of peptide hydrogels as effective hemostatic agents.

One-pot construction of degradable, stretchable, cytocompatible and transparent hydrogel for potential fresh-keeping film alternatives

Fresh postharvest fruits and vegetables are severely wasted due to quality deterioration, such as moisture loss or microbial infection. The widely used plastic fresh-keeping film has been questioned for its environmental and food safety concerns, so it is urgent to develop green plastic alternatives. In this paper, carboxymethyl cellulose/polyvinyl alcohol hydrogel was efficiently prepared by a one-pot method at room temperature driven by multiple covalent crosslinking and hydrogen bonding. The results showed that the hydrogel exhibited uniform and regular porous structure, satisfactory tensile strength (7934 Pa), tensile elongation (483.27 %), soil degradability (complete degradation within 45 days), transparency and cytocompatibility. Considering the advantages of simple preparation, biodegradability and excellent performance, CMC/PVA hydrogel is expected to attract wide attention as a novel degradable fresh-keeping film in fruit and vegetable preservation.

Block Sequence Effects on the Self-Assembly Behaviors of Polypeptide-Based Penta-Block Copolymer Hydrogels.

Peptide-based hydrogels have great potential for applications in tissue engineering, drug delivery, and so on. We systematically synthesize, characterize, and investigate the self-assembly behaviors of a series of polypeptide-based penta-block copolymers by varying block sequences and lengths. The copolymers contain hydrophobic blocks of poly(γ-benzyl-l-glutamate) (PBG, Bx) and two kinds of hydrophilic blocks, poly(l-lysine) (PLL, Ky) and poly(ethylene glycol) (PEG, EG34), where x and y are the number of repeating units of each block, where PBG and PLL blocks have unique functions for nerve regeneration and cell adhesion. It shows that a sufficient length of the middle hydrophilic segment capped with hydrophobic end PBG blocks is required. They first self-assemble into flower-like micelles and sequentially form transparent hydrogels (as low as 2.3 wt %) with increased polymer concentration. The hydrogels contain a microscale porous structure, a desired property for tissue engineering to facilitate the access of nutrient flow for cell growth and drug delivery systems with high efficiency of drug storage. We hypothesize that the structure of Bx-Ky-EG34-Ky-Bx agglomerates is beyond micron size (transparent), while that of Ky-Bx-EG34-Bx-Ky is on the submicron scale (opaque). We establish a working strategy to synthesize a polypeptide-based block copolymer with a wide window of sol-gel transition. The study offers insight into rational polypeptide hydrogel design with specific morphology, exploring the novel materials as potential candidates for neural tissue engineering.

Transparent multifunctional cellulose-based conductive hydrogel for wearable strain sensors and arrays

Conductive hydrogels as promising candidate materials for flexible strain sensors have gained considerable attentions. However, it is still a great challenge to construct hydrogel with multifunctional performance via natural polymer. Herein, a novel multifunctional conductive hydrogel based on methylcellulose and cellulose nanocrystal was prepared via a facile and low-cost strategy. Methylcellulose (MC) was introduced to not only guarantee the stability of tannic acid coated cellulose nanocrystal (TA@CNCs) in LiCl solution, but also improve anti-freezing ability. The obtained hydrogel exhibited high transparency (98 % at 800 nm), good stretchability (663.1 %), low temperature tolerance (−23.9 °C), superior conductivity (2.89 S/m) and excellent UV shielding behavior. Flexible strain sensor assembled by the prepared hydrogels can be used to detect human body motions include subtle and large motions, and exhibited good sensitivity and stability over a wide temperature range. Multiple flexible hydrogels can also be assembled into a 3D sensor array to detect the distribution and magnitude of spatial pressure. Therefore, the hydrogels prepared via natural polymers will have broad application prospects in wearable devices, electronic skin and multifunctional sensor components.

A Transparent Hydrogel-Ionic Conductor with High Water Retention and Self-Healing Ability.

This study presents a transparent and ion-conductive hydrogel with suppressed water loss. The hydrogel comprises agarose polymer doped with sucrose and sodium chloride salt (NaCl-Suc/A hydrogel). Sucrose increases the water retention of the agarose gel, and the Na and Cl ions dissolved in the gel provide ionic conductivity. The NaCl-Suc/A gel shows high retention capability and maintains a 45% water uptake after 4 h of drying at 60 °C without encapsulation at the optimum gel composition. The doped NaCl-Suc/A hydrogel demonstrates improved mechanical properties and ionic conductivity of 1.6 × 10-2 (S/cm) compared to the pristine agarose hydrogel. The self-healing property of the gel restores the electrical continuity when reassembled after cutting. Finally, to demonstrate a potential application of the ion-conductive hydrogel, a transparent and flexible pressure sensor is fabricated using the NaCl-Suc/A hydrogel, and its performance is demonstrated. The results of this study could contribute to solving problems with hydrogel-based devices such as rapid dehydration and poor mechanical properties.

Development of ZmT-PEG hydrogels through Michael addition reaction and protein self-assembly for 3D cell culture.

Bioactive protein-derived hydrogels are highly attractive three-dimensional (3D) platforms for in vitro cell culture. However, most protein and polypeptide hydrogels are extracted from animal tissues or chemically synthesized, with many drawbacks. Herein, we fabricated an optically transparent ZmT-PEG hydrogel via a facile one-pot strategy. The modified Z1Z2 (Zm) was obtained by introducing cysteine at the C-terminus of Z1Z2 (ZC) and inserting the RGD sequence into the low conserved (CD) loop (ZR). A Michael addition reaction occurred between Zm and 4-arm PEG-MAL, and Zm-PEG self-assembled with truncated Telethonin (Tm) to form the hydrogel. We expressed the Zm and Tm proteins in Escherichia coli. CD spectroscopy showed that genetic modification and the reaction with 4-arm PEG-MAL had no effect on the secondary structure of the Zm protein. When Zm was at 10 wt% and the ratio of Zm : 4-arm PEG-MAL : Tm was 2 : 1 : 1, the gelation time was 6-8 hours. SEM results revealed that the hydrogels had an interconnected porous structure with pore diameters of 20-150 μm. Cell experiments showed that MCF-7 cells could grow and proliferate significantly on the hydrogel after 7 days of culture. Immunofluorescence results suggested that MCF-7 cells on the ZmT hydrogel had a spherical structure similar to that on Matrigel. These results indicate that the ZmT-PEG hydrogel can be used for cell culture in vitro and is promising for large-scale production.

A tough and piezoelectric poly(acrylamide/N,N-dimethylacrylamide) hydrogel-based flexible wearable sensor.

A flexible, tough, highly transparent and piezoelectric polyacrylamide hydrogel was fabricated induced by blue light photocuring, with camphorquinone/diphenyliodonium hexafluorophosphate (CQ/DPI) as the blue light initiator, acrylamide (AM) and N,N-dimethylacrylamide (DMAA) as monomers, polyethylene glycol diacrylate (PEGDA) as the crosslinker, lecithin as the dispersant, and BaTiO3 as the piezoelectric material. Various performance tests were carried out on the hydrogel, and the results showed that lecithin enhances the dispersion of BaTiO3 within the system and improves the tensile properties (>100% strain) of the hydrogel, and the addition of PEGDA not only improves the photopolymerization performance of the hydrogel, but also significantly improves its fracture strength (∼0.3 MPa). In addition, BaTiO3 enables the resultant hydrogels to show excellent conductivity (>1.5) and stable response to strain. The assembled hydrogel sensor shows a sensitive response to human joint activities, which is expected to be applied in self-powered sensors and energy collection.

Sensitive label free imaging of 3D cell models with minimal toxicity using confocal reflectance.

Confocal reflectance imaging typically suffers from high background and poor sensitivity. We demonstrate sensitive and low-background reflectance imaging of cells encapsulated in transparent 3D hydrogels. Nanoscale cell morphology is visualized with sensitivity similar to confocal fluorescence, with low laser power, minimal specimen preparation, and reduced toxicity.

Highly transparent and strong nanohesive hydrogel patch for tissue adhesion

This research aimed to design and fabricate a biocompatible dual-layer chitosan hydrogel adhesive patch with exceptional mechanical properties by employing a nanoadhesive strategy to assess its tissue adhesion performance. The design involves physical cross-linking to construct a robust chitosan hydrogel as a backing membrane, followed by in situ photocuring to create the adhesive hydrogel layer, resulting in an integrated chitosan hydrogel adhesive patch. To facilitate adhesion between the hydrogel patch and biological tissue, surface-activated silica nanoparticles serve as interfacial connectors, analogous to nanoglue, promoting binding of the hydrogel to the substrate. Characterization of the patch reveals an adhesive energy of 282 J/m&lt;sup&gt;2&lt;/sup&gt; to biological tissues in vitro and a burst pressure of 450 mmHg (1 mmHg=0.133 kPa). The patch exhibits outstanding mechanical properties, with a tensile strength of 4.3 MPa, an elongation rate of 65%, and a fracture toughness of 3.82 kJ/m&lt;sup&gt;2&lt;/sup&gt;. Additionally, the nanohesion-based chitosan hydrogel adhesive patch is highly transparent and demonstrates excellent biocompatibility. It holds promise for applications in various biomedical fields, including tissue repair and drug delivery, thereby providing a robust material foundation for advancements in clinical surgery.

Injectable alginate-based in situ self-healable transparent hydrogel as a vitreous substitute with a tamponading function

Retinal detachment and other vision-threatening disorders often necessitate vitreous body removal and tamponade injection for retina stabilization. Current clinical tamponades such as silicone oil and expansile gases have drawbacks, including patient discomfort and the need for secondary surgery. We introduce a transparent alginate-phenylboronic acid/polyvinyl alcohol composite hydrogel (TALPPH) as a novel vitreous substitute with tamponading capabilities. In vitro physicochemical, rheological, and optical characterization of in situ self-healable TALPPH was performed, and long-term biocompatibility was assessed in a rabbit model of vitrectomy retinal detachment. In vivo evaluations confirmed TALPPH's ability to inhibit retinal detachment recurrence and preserve rabbit vision without adverse effects. TALPPH's close resemblance to the natural vitreous body suggests potential as a vitreous tamponade substitute for future ophthalmological applications.

Biomimicking natural wood to fabricate isotropically super-strong, tough, and transparent hydrogels for strain sensor and triboelectric nanogenerator applications

We describe an efficient wood-inspired biomimicking strategy integrating multiscale structures to synthesize isotropically strong, tough, conductive, and transparent hydrogels as strain sensors and self-powered triboelectric nanogenerators.

Electron-Beam-Initiated Crosslinking of Methacrylated Alginate and Diacrylated Poly(ethylene glycol) Hydrogels.

An ideal wound dressing not only needs to absorb excess exudate but should also allow for a moist wound-healing environment as well as being mechanically strong. Such a dressing can be achieved by combining both a natural (alginate) and synthetic (poly(ethylene glycol) polymer. Interestingly, using an electron beam on (meth)acrylated polymers allows their covalent crosslinking without the use of toxic photo-initiators. The goal of this work was to crosslink alginate at different methacrylation degrees (26.1 and 53.5% of the repeating units) with diacrylated poly(ethylene glycol) (PEGDA) using electron-beam irradiation at different doses to create strong, transparent hydrogels. Infrared spectroscopy showed that both polymers were homogeneously distributed within the irradiated hydrogel. Rheology showed that the addition of PEGDA into alginate with a high degree of methacrylation and a polymer concentration of 6 wt/v% improved the storage modulus up to 15,867 ± 1102 Pa. Gel fractions > 90% and swelling ratios ranging from 10 to 250 times its own weight were obtained. It was observed that the higher the storage modulus, the more limited the swelling ratio due to a more crosslinked network. Finally, all species were highly transparent, with transmittance values > 80%. This may be beneficial for the visual inspection of healing progression. Furthermore, these polymers may eventually be used as carriers of photosensitizers, which is favorable in applications such as photodynamic therapy.

A transparent synthetic peptide hydrogel as a haemostatic agent in athermal nerve sparing robot-assisted radical prostatectomy: an observational study.

PuraStat® is a new synthetic haemostatic agent constituting peptides that self-assemble into sheets when exposed to ionic charges. The objective of this submission is to assess the perioperative, functional and user-reported outcomes of PuraStat® as an athermal topical haemostatic agent for use on the neurovascular bundle (NVB) in robot-assisted radical prostatectomy (RARP), and to inform further research into this developing field. Demographic and disease data for 29 consecutive patients undergoing RARP were recorded. PuraStat® was used as the primary haemostatic agent to the NVB, without thermal or suture haemostasis, unless necessary. Preoperative, 1-h postoperative and 24-h postoperative haemoglobin (Hb) were measured. Operative data including postoperative complications up to 30 days were noted. Urinary function, continence and erectile function (EF) were measured pre- and postoperatively with the International Prostate Symptom Score (IPSS), patient reporting of pad usage, and International Index of Erectile Function (IIEF)-5 respectively. A qualitative assessment of PuraStat® was made intraoperatively by the surgical assistant in the following categories: transparency, haemostatic efficacy, ready-to-use, handling, and overall satisfaction. Twenty-nine males aged between 49 and 75 years underwent a nerve-sparing RARP under a single surgeon for clinically significant prostate cancer with PuraStat® used as the primary haemostatic agent at the NVB. One patient required an additional haemostatic suture. The median prostate volume was 36 mL. Mean blood loss was 363 mL. The mean Hb at 1 and 24 h postoperative was 135.2 and 125.1 mg/dL. Median Hb change from 1-24 h postoperative was 11 mg/dL. No transfusions were required, and there were no postoperative complications. Urinary function and continence were preserved. EF in our series was lower than published data. Our observational study suggests that PuraStat® is a safe haemostatic agent in RARP with similar perioperative bleeding outcomes, comparable long-term urinary outcomes and a high level of intraoperative user satisfaction. The effects on EF requires further investigation. PuraStat® appears to be a useful therapeutic tool for the urologist performing RARPs.