Acid Hydrogel Research Articles

A comprehensive investigation of cholesteric liquid crystal interpenetrating polymer networks for metal ion sensor technology

This study outlines the fabrication process of a photonic polymer cholesteric liquid crystal (PCLC) engineered for dynamic response to external stimuli. The methodological framework includes the precise templating of PCLC onto an interpenetrating polymer network (IPN) following selective UV crosslinking and the careful removal of nonreactive mesogens. The sensor component of the PCLC film is composed of poly(acrylic acid) hydrogel. A key aspect of the process involves the formation of micro-holes through acetone treatment to enhance sensitivity. Additionally, functionalization with potassium hydroxide (KOH) improves the detection of calcium ions (Ca2+) by disrupting hydrogen bonds and facilitating the formation of potassium carboxylate salt. Combining the inherent properties of PCLC with the hydrogel’s responsiveness to metal ions results in a sophisticated sensor designed to detect Ca2+ ions through the modulation of PCLC pitch, creating distinct transmission bands. The manuscript provides a detailed quantitative analysis of stimulus-induced changes in PCLC wavelength, using measured spectra to refine and optimize process conditions. The resulting PCLC sensor demonstrates exceptional sensitivity (9.30 nm/mM) within the 1–15 mM Ca2+ ion concentration range, along with excellent specificity. This cost-effective, user-friendly, and colorimetric sensing modality holds significant promise for various applications in analytical chemistry.

Entrapment of glucose oxidase from Aspergillus niger ISL-09 in poly(acrylamide-co-acrylic acid) hydrogels for improved stability and catalytic efficiency towards industrial applications

The present study highlights the true potential of Aspergillus niger ISL-09 to produce glucose oxidase (GOx) and focuses on improving the catalytic properties of GOx by entrapping it in poly acrylamide-co-acrylic acid (AAm-co-AAc) hydrogels, fabricated by free-radical polymerization method. For this purpose, the optimum conditions for GOx activity were found to be: 15 g soybean meal (SBM) substrate, 20 mL moisture content, 96 h incubation period, and 1.5 mL of fungal spore suspension. The purified extracellular GOx was observed to have 32.4% yield, with 0.02 U/mg specific activity and approximately 80 kDa subunit molecular weight. The GOx was most active at pH 5.5 and 40 °C. The immobilization of GOx in poly (AAm-co-AAc) hydrogels led towards improved stability and catalytic efficiency, resulting in a 21.7% increase in activity compared to free enzyme. The study also examined the potential of GOx in the pharmaceutical and textile industries as Ca-gluconate producer and bleaching agent, respectively. The study concludes that A. niger ISL-09 is a promising source for GOx production under optimal conditions. Furthermore, the immobilization of GOx in poly (AAm-co-AAc) hydrogels can significantly improve its catalytic properties, making it suitable for different industrial applications. However, further scaling up is required for the better implementation in industry.

A vascular endothelial growth factor-loaded chitosanhyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke.

Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemia-reperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor-loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor-loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.

Novel Supramolecular Hydrogel for Infected Diabetic Foot Ulcer Treatment.

Multifunctional responsive hydrogels hold significant promise for diabetic foot ulcer (DFU) treatment, though their complex design and manufacturing present challenges. This study introduces a novel supramolecular guanosine-phenylboronic-chlorogenic acid (GBC) hydrogel developed using a dynamic covalent strategy. The hydrogel forms through guanosine quadruplex assembly in the presence of potassium ions and chlorogenic acid (CA) linkage via dynamic borate bonds. GBC hydrogels exhibit pH and glucose responsiveness, releasing more chlorogenic acid under acidic and high glucose conditions due to borate bond dissociation and G-quadruplex (G4)hydrogel disintegration. Experimental results indicate that GBC hydrogels exhibit good self-healing, shear-thinning, injectability, and swelling properties. Both in vitro and in vivo studies demonstrate the GBC hydrogel's good biocompatibility, ability to eliminate bacteria and reactive oxygen species (ROS), facilitate macrophage polarization from the M1 phenotype to the M2 phenotype (decreasing CD86 expression and increasing CD206 expression), exhibit anti-inflammatory effects (reducing TNF-α expression and increasing IL-10 expression), and promote angiogenesis (increasing VEGF, CD31, and α-SMA expression). Thus, GBC hydrogels accelerate DFU healing and enhance tissue remodeling and collagen deposition. This work provides a new approach to developing responsive hydrogels to expedite DFU healing.

A modified hyaluronic acid hydrogel with strong bacterial capture and killing capabilities for drug-resistant bacteria-infected diabetic wound healing

Management of diabetic wounds becomes increasingly challenging as bacterial infections intensify the inflammation. Employing polysaccharide hydrogels with inherent antibacterial qualities can significantly reduce the need for antibiotics to manage infections in diabetic wounds. The typical approach to achieving antibacterial outcomes with hydrogels relies on the penetration of bacteria into their porous architecture. Such penetration not only takes time but can also prolong inflammation, thus impeding the healing of wounds. Hence, the quick capture and eradication of bacteria are essential for optimizing the hydrogel's antibacterial performance. Herein, we introduce a multifunctional polysaccharide hydrogel dressing—designated as HAQ—created for managing bacterial infections in diabetic wounds. This dressing is based on hyaluronic acid, which is modified with methacrylic anhydride, and special functional groups are added to the modified hyaluronic acid matrix: phenylboronic acid for capturing bacteria and quaternary ammonium chitosan for bacterial destruction. As expected, the HAQ system exhibits robust antibacterial effectiveness against both methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa in vitro and in vivo. Consequently, HAQ stands as a promising hydrogel dressing with intrinsic antibacterial capabilities and offers significant potential for managing diabetic wounds infected by drug-resistant bacteria.

The Effect of Polynucleotide‐Hyaluronic Acid Hydrogel in the Recovery After Mechanical Skin Barrier Disruption

ABSTRACTBackgroundThe epidermal barrier acts as a defense against external agents as well as helps to maintain body homeostasis. Polynucleotides (PN), exogenous DNA fragments, promote wound repair through their stimulatory and anti‐inflammatory effects. Recent findings indicate a synergistic effect of PN and hyaluronic acid (HA) combinations in regulating inflammation and promoting cell proliferation. This study aims to elucidate the effects of PN and HA on repairing the epidermal barrier following its disruption by tape stripping (TS) in a mouse model.Materials and MethodsAfter disrupting the epidermal barrier using TS, a formulation containing PN (14 mg/mL) and HA (6 mg/mL) was applied. Trans‐epidermal water loss (TEWL) was measured at 0, 3, 6, 24, 48, and 72 h. Mice were euthanized after the final application at 72 h, and tissue samples were analyzed for epidermal/dermal thickness, neutrophil infiltration, and filaggrin expression.ResultsWe observed a significant reduction in TEWL in the PN+HA group compared to that in the control group (20.8 ± 0.5 vs. 43.7 ± 0.5 g/m2h at 72 h, p < 0.05), indicating an improvement in barrier function. Histological evaluation showed decreased epidermal and dermal thickening in the PN+HA group compared to that in the control group (epidermal: 29.4 ± 2.2 vs. 57.9 ± 3.5 μm; dermal: 464.8 ± 25.9 vs. 825.9 ± 44.8 μm, both p < 0.05). Additionally, neutrophil infiltration in the dermis was significantly reduced, and filaggrin protein levels were significantly higher in the PN+HA group compared to those in the control group (4.8 ± 0.4 vs. 21.1 ± 3.3 for neutrophils; 0.84 ± 0.04 vs. 0.42 ± 0.03 for filaggrin, both p < 0.05).ConclusionThese results suggest that PN+HA may be an effective therapeutic strategy for repairing skin barrier damage.

Rapid, Micron-Resolution 3D Printing of Nd:YAG Ceramic with Optical Gain.

Polycrystalline yttrium aluminum garnet (YAG) ceramic doped with neodymium (Nd), referred to as Nd:YAG, is widely used in solid-state lasers. However, conventional powder metallurgy methods suffer from expenses, time consumption, and limitations in customizing structures. This study introduces a novel approach for creating Nd:YAG ceramics with 3D free-form structures from micron (∼70µm) to centimeter scales. Firstly, sol-gel synthesis is employed to form photocurable colloidal solutions. Subsequently, by utilizing a home-built micro-continuous liquid interface printing process, precursors are printed into 3D poly(acrylic acid) hydrogels containing yttrium, aluminum, and neodymium hydroxides, with a resolution of 5.8µm pixel-1 at a speed of 10µm s-1. After the hydrogels undergo thermal dehydration, debinding, and sintering, polycrystalline Nd:YAG ceramics featuring distinguishable grains are successfully produced. By optimizing the concentrations of the sintering aids (tetraethyl orthosilicate) and neodymium trichloride (NdCl3), the resultant samples exhibit satisfactory photoluminescence, emitting light concentrated at 1064nm when stimulated by a 532nm laser. Additionally, Nd:YAG ceramics with various 3D geometries (e.g., cone, spiral, and angled pillar) are printed and characterized, which demonstrates the potential for applications, such as laser and amplifier fibers, couplers, and splitters in optical circuits, as well as gain metamaterials or metasurfaces.

Thermo-sensitive poly(amino acid) hydrogel mediates cytoprotection through an antioxidant mechanism

Oxidative stress, characterized by the excessive accumulation of reactive oxygen species (ROS), is linked to various pathological conditions, including myocardial infarction, cancer, and neurodegenerative diseases. Addressing ROS-induced cell damage has become a critical focus of biomedical research. In this study, a thermo-sensitive poly(amino acid) hydrogel, composed of poly(ethylene glycol)-block-poly(L-methionine), was prepared for cytoprotection through ROS scavenging. The sol-to-gel transition mechanism of the hydrogel was elucidated, and its potent antioxidant properties and cell protective effects were validated using hydrogen peroxide (H2O2)-induced oxidative stress and oxygen-glucose deprivation (OGD) models. The hydrogel significantly mitigated H2O2-induced damage in L929 cells, doubling their survival rate. Additionally, it scavenged approximately 35.8% of the ROS during OGD, reducing mitochondrial oxidative damage and resulting in a 29.4% decrease in apoptotic cell numbers. These findings underscore the potential biomedical applications of thermo-sensitive poly(amino acid) hydrogels, particularly in treating oxidative stress-related cell damage.

Mangostanin hyaluronic acid hydrogel as an effective biocompatible alternative to chlorhexidine

Periodontal disease (PD) prevention and treatment products typically demonstrate excellent antibacterial activity, but recent studies have raised concerns about their toxicity on oral tissues. Therefore, finding a biocompatible alternative that retains antimicrobial properties is imperative. In this study, a chemically modified hyaluronic acid (HA) hydrogel containing mangostanin (MGTN) was developed. Native HA was chemically modified, incorporating amino and aldehyde groups in different batches of HA, allowing spontaneous crosslinking and gelation when combined at room temperature. MGTN at different concentrations was incorporated before gelation. The structure, swelling characteristics MGTN release, rheological parameters, and in vitro degradation performance of the loaded hydrogel were first evaluated in the study. Then, antimicrobial properties were tested on Porphyromonas gingivalis and its biocompatibility in 3D-engineered human gingiva. HA hydrogel was very stable and showed a sustained release for MGTN for at least 7 days. MGTN-loaded HA hydrogel showed equivalent antimicrobial activity compared to a commercial gel of HA containing 0.2 % chlorhexidine (CHX). In contrast, while MGTN HA hydrogel was biocompatible, CHX gel showed high cytotoxicity, causing cell death and tissue damage. Modified HA hydrogel allows controlled release of MGTN, resulting in a highly biocompatible hydrogel with antibacterial properties. This hydrogel is a suitable alternative therapy to prevent and treat PD.

Bioinspired Green Underwater Adhesive Gelatin‐Tannic Acid Hydrogel With Wide Range Adjustable Adhesion Strength and Multiple Environmental Adaptability

Bioinspired Green Underwater Adhesive Gelatin‐Tannic Acid Hydrogel With Wide Range Adjustable Adhesion Strength and Multiple Environmental Adaptability

Formulation and evaluation of salicylic acid hydrogel based on hydrotropic solubility enhancement technique

Background and objective: Salicylic acid (SA) has keratolytic activities and it is used topically to treat dandruff and seborrheic dermatitis. The hydrotropic phenomenon in pharmaceutical preparations is utilized to enhance the solubility of water-insoluble drug molecules that promoted to prepare the salicylic acid as a hair gel for local effect and it can extend its keratolytic action for a longer period compared to the salicylic acid solution. Methods: Preformulation study was performed to exclude any unwanted chemical interaction between SA and excipients using Fourier-transform infrared spectroscopy (FTIR). The solubility of SA was determined separately in sodium acetate and sodium citrate solutions at a concentration of 1, 3, and 5 %w/v, using distilled water as a solvent. An optimum gel formulation was developed and it was used to prepare the SA gel formulation. Characterizations were performed in terms of physical appearance, viscosity, pH, and spreadability, in-vitro studies were performed in physiological pH, and ex-vivo diffusion studies were performed utilizing rats’ skin. Results: FTIR did not show any chemical interaction between the drug and sodium citrate. The hydrotropic solution of sodium citrate with a concentration of 5% w/v increased the solubility of SA by 28 folds, while the sodium acetate solutions with a concentration of 5% w/v increased the solubility of SA by 19 folds. The optimum gel formula (F1) with a drug content of 97% showed a slow dissolution rate and minimum diffusion through the skin. Conclusion: The hydrotropic solubilization technique significantly influenced the solubilization of salicylic acid in the water and the highest solubility rate was achieved from 5% w/v sodium citrate solution. The formulated hydrogels using carbopol 971P as gelling agent decreased the diffusion rate of SA.

Hyaluronic acid-alginate hydrogel stimulates the differentiation of neonatal mouse testicular cells into hepatocyte-like and other cell lineages in three-dimensional culture.

Extracellular matrix (ECM)-derived hydrogels are frequently used in three-dimensional (3D) cell culture and organoid formation in several tissues. However, in the 3D cultivation of testicular cells, the hyaluronic acid (HA) hydrogel has not received as much attention. This study examined the effects of three distinct composites, including HA-alginate (HA-Alg), HA-alginate-collagen (HA-Alg-Col), and HA-alginate-decellularized ECM (HA-Alg-dECM), on mouse testicular cell culture and in vitro spermatogenesis. For the creation of composites, the concentration of biomaterials used was 0.5% HA, 1% alginate, 2.5mg/mL collagen, and 25mg/mL dECM derived from the testicles of Rams. After 3D culture of 5 days post-partum (dpp) mouse testicular cells for 14 days, HA-Alg was selected as a superior composite due to the greater number and size of the produced organoids. Then, cell culture was rerun by HA-Alg for 14 days, which was later extended for an additional 28 days. In addition, the 3D culture of 10 dpp mouse testicular cells was used to compare with 5 dpp mice on day 14. The morphology and gene expression were analyzed using appropriate techniques. On day 14, the HA-Alg hydrogel showed significantly more organoids in terms of size and number than the other two groups (p<0.05); nevertheless, none of the groups showed the expected signs of testis organoids. Remarkably, on day 14, the histology and immunostaining tests revealed features of hepatocyte-like cells (HLCs) and albumin production as a marker of HLC functionality. Furthermore, the analysis of gene expression verified the significant expression of angiogenesis markers (p<0.01). After the extended culture to 28 days, 5 dpp testicular cells once more differentiated into erythrocytes and HLCs, while a small number of organoids showed the characteristic of renal cells. Cell culture of 10 dpp mice for 14 days showed a wide range of cell lineages, including renal, glandular, chondrocyte, and hepatocyte-like cells in comparison to the 5 dpp mice. While the HA-Alg composite did not support spermatogenesis in the 3D culture of mouse testicular cells, it demonstrated an unpredicted potential for promoting the differentiation of neonate mouse testicular cells into HLC, erythrocytes, and other cell lineages.

Collagen VI deposition primes the glioblastoma microenvironment for invasion through mechanostimulation of β-catenin signaling.

While glioblastoma (GBM) progression is associated with extensive extracellular matrix (ECM) secretion, the causal contributions of ECM secretion to invasion remain unclear. Here we investigate these contributions by combining engineered materials, proteomics, analysis of patient data, and a model of bevacizumab-resistant GBM. We find that GBM cells cultured in engineered 3D hyaluronic acid hydrogels secrete ECM prior to invasion, particularly in the absence of exogenous ECM ligands. Proteomic measurements reveal extensive secretion of collagen VI, and collagen VI-associated transcripts are correspondingly enriched in microvascular proliferation regions of human GBMs. We further show that bevacizumab-resistant GBM cells deposit more collagen VI than their responsive counterparts, which is associated with marked cell-ECM stiffening. COL6A3 deletion in GBM cells reduces invasion, β-catenin signaling, and expression of mesenchymal markers, and these effects are amplified in hypoxia. Our studies strongly implicate GBM cell-derived collagen VI in microenvironmental remodeling to facilitate invasion.

Multi-responsive sodium hyaluronate/tannic acid hydrogels with ROS scavenging ability promote the healing of diabetic wounds

Oxidative stress caused by excessive reactive oxygen species (ROS) accumulation significantly hinders wound healing in patients with diabetes. Scavenging ROS and reducing inflammation are crucial for rapid healing. In this work, a multi-responsive sodium hyaluronate (HA)/tannic acid (TA) hydrogel was developed based on boronate ester bonds. Sodium hyaluronate with 3-aminophenyl boronic acid modification (HA-APBA) was mixed and crosslinked with TA to form HA-APBA/TA hydrogels. These hydrogels are injectable, self-healing, and biocompatible. The HA-APBA/TA hydrogels could release free TA through the collapse of the structure at low pH, high H2O2 concentration, and high glucose concentration, thus possessing good ROS scavenging ability. In full-thickness skin wounds of db/db mice, the HA-APBA/TA hydrogels promoted wound healing, collagen deposition, and significant angiogenesis. Furthermore, they have been shown to effectively reduce the levels of inflammatory factors in wounds and lower the expression of CD86, a pro-inflammatory macrophage surface marker. This resulted in a more effective transition of wound healing from the inflammatory phase to the proliferative phase. This study provides an optional strategy for alleviating oxidative stress and controlling excessive inflammation, thereby promoting diabetic wound healing.

Caffeic Acid and Cyclen-Based Hydrogel for Synergistic Antibacterial Therapy.

Caffeic acid is a natural product that contains both phenolic and acrylic functional groups and has been widely employed as an alternative drug to combat chronic infections induced by microbes such as bacteria, fungi, and viruses. Several strategies, including derivatization and nanoformulation, have been applied in order to overcome the issues of water insolubility, poor stability, and the bioavailability of caffeic acid. Here, caffeic acid and cyclen-Zn(II) are incorporated into a G4-assembly by using a phenylborate linker to form the mixed supramolecular prodrug GB-CA/Cy-Zn(II) hydrogel. The delivery system is expected to enhance antibacterial and anti-inflammatory properties during the wound healing process through the synergistic effect of caffeic acid and cyclen-Zn(II). The preparation and physicochemical and mechanical properties of the hydrogel were investigated by NMR, CD, TEM, and rheological assays. The typical inflammatory cytokines and in vitro antibacterial experiments indicated that inflammation and infection can be significant suppressed by the hydrogel treatment. An in vivo infected wound model treated by the hydrogel showed rapid wound healing capacity and biosafety. The current work depicts a simple method to prepare a caffeic acid hydrogel carrier, which facilitates synergistic treatment for inflammation and bacterial infections at the wound site.

Optical characterization of a new composition of acrylic acid hydrogel dosimeter for quality assurance in radiotherapy treatment

Optical characterization of a new composition of acrylic acid hydrogel dosimeter for quality assurance in radiotherapy treatment

Genetically Encoded Incorporation of IFN-α into Collagen-like Protein–Hyaluronic Acid Hydrogels for Diabetic Chronic Wound Healing

Genetically Encoded Incorporation of IFN-α into Collagen-like Protein–Hyaluronic Acid Hydrogels for Diabetic Chronic Wound Healing

Novel “Signal-On” photoelectrochemical assay by regulating the release of cationic dyes with the utilization of target-specific enzymolysis hydrogels

Targeted response-based controlled release strategy exhibits high specificity and sensitivity in many biomedical applications. In this paper, we report a novel and simple “signal-on” photoelectrochemical (PEC) assay strategy, which regulates the release of cationic dyes through the utilization of target-specific enzymolysis hydrogel. The cationic dye crystal violet (CV) embedded in the hyaluronic acid (HA) hydrogel was released in the presence of hyaluronidase (HAase) and increased the cathodic photocurrent of BiOBr nanoflowers. The cathodic photocurrent response is linear with the logarithm of HAase activity in the range of 0.10–120 U/mL, with an ultralow detection limit of 0.034 U/mL detected. Our work provides a simple and efficient strategy to detect HAase activity by monitoring the enzyme response of hydrogel-controlled release photosensitizer, which is expected to be able to provide an efficient strategy for early clinical diagnosis of some other diseases and meet the ever-increasing needs in pharmaceutical and medical fields.

Facile preparation and performance of flexible sensors based on polyacrylamide/carboxymethylchitosan/tannin acid hydrogels

AbstractHydrogel flexible sensors are gaining significant interest due to their distinct biocompatibility, flexibility, and unique features of being adjustable and injectable, but there are still problems of poor self‐healing performance and low conductivity in the current stage of research. In this work, a prefabricated blending method was used to construct a dual‐network system using polyacrylamide (PAM), carboxymethyl chitosan (CMCS), and tannin acid (TA), and ferric ions (Fe3+) were introduced to apply ionically conductive organic hydrogels to flexible sensors. The PAM/CMCS‐Fe3+/TA hydrogels have good fatigue resistance and self‐healing properties, and their conductivity is as high as 6.42 S/m. This hydrogel‐based sensor for strain sensing purpose offers a lot of promise for flexible sensor applications since it can provide steady, dependable, and repeatable electrical impulses.

In Situ-Forming, Bioorthogonally Cross-linked, Nanocluster-Reinforced Hydrogel for the Regeneration of Corneal Defects.

Corneal defects can lead to stromal scarring and vision loss, which is currently only treatable with a cadaveric corneal transplant. Although in situ-forming hydrogels have been shown to foster regeneration of the cornea in the setting of stromal defects, the cross-linking, biomechanical, and compositional parameters that optimize healing have not yet been established. This, Corneal defects are also almost universally inflamed, and their rapid closure without fibrosis are critical to preserving vision. Here, an in situ forming, bioorthogonally cross-linked, nanocluster (NC)-reinforced collagen and hyaluronic acid hydrogel (NCColHA hydrogel) with enhanced structural integrity and both pro-regenerative and anti-inflammatory effects was developed and tested within a corneal defect model in vivo. The NCs serve as bioorthogonal nanocross-linkers, providing higher cross-linking density than polymer-based alternatives. The NCs also serve as delivery vehicles for prednisolone (PRD) and the hepatocyte growth factor (HGF). NCColHA hydrogels rapidly gel within a few minutes upon administration and exhibit robust rheological properties, excellent transparency, and negligible swelling/deswelling behavior. The hydrogel's biocompatibility and capacity to support cell growth were assessed using primary human corneal epithelial cells. Re-epithelialization on the NCColHA hydrogel was clearly observed in rabbit eyes, both ex vivo and in vivo, with expression of normal epithelial biomarkers, including CD44, CK12, CK14, α-SMA, Tuj-1, and ZO-1, and stratified, multilayered morphology. The applied hydrogel maintained its structural integrity for at least 14 days and remodeled into a transparent stroma by 56 days.