Naewon Kang

All Publications

• Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels. NPJ Regenerative medicine Chen, F., Han, U., Wungcharoen, T., Seo, Y. A., Le, P., Jiang, L., Kang, N. W., Song, E., Jang, K., Mundy, D., Fernandes-Cunha, G. M., Heilshorn, S., Myung, D. 2025; 10 (1): 8

  Abstract

  Corneal transplantation is the primary treatment for corneal blindness, affecting millions globally. However, challenges like donor scarcity and surgical complications remain. Recently, in situ-forming corneal stroma substitutes have emerged, offering potential solutions to these limitations. These substitutes enable liquid-to-hydrogel formation in situ, eliminating sutures and reducing complications. Here we performed a direct, side-by-side comparison of a composite hyaluronan-collagen (HA-Col) hydrogel crosslinked by either photochemistry or bio-orthogonal chemistry to ascertain the impact of reaction specificity on corneal wound healing. Testing in rodent and rabbit models suggests that composite HA-Col gels crosslinked by bio-orthogonal chemistry results in more rapid and optically favorable wound healing compared to the same composition crosslinked by photochemistry as well as bio-orthogonally crosslinked collagen alone. These findings underscore biochemical parameters that may be important to the success of crosslinked, in situ-forming hydrogels as an alternative to corneal transplantation, with the potential for expanded access to treatment and improved outcomes.

  View details for DOI 10.1038/s41536-024-00385-9

  View details for PubMedID 39905045

  View details for PubMedCentralID 3872837

• Radiopaque hydrogel-in-liposomes towards theranostic applications for malignant tumors. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Lee, S. M., Yoo, S. Y., Kim, T., Kim, N., Kang, J., Lim, K. Y., Kim, M., Choo, S., Lee, H. S., Kim, H., Kang, N. W., Chaudhary, M., Bikram, K., Lee, W., Cho, C. W., Kim, D. D., Kim, K. T., Lee, J. Y. 2025; 183: 117822

  Abstract

  A radiopaque hydrogel-in-liposome (RHL) system was developed for micro-computed tomography (μCT) imaging of tumor tissue and simultaneous delivery of a cytotoxic agent. Iopamidol (IPD) and doxorubicin (DOX) were incorporated as the CT contrast and anti-cancer agents, respectively. The presence of a polyethylene glycol hydrogel core in the liposomes was confirmed via attenuated total reflectance Fourier transform infrared, proton nuclear magnetic resonance, and selective solvent extraction. Nano-sized (∼160 nm) spherical DOX/IPD-loaded RHLs with a narrow size distribution and negative zeta potential were successfully fabricated. The RHLs demonstrated enhanced cellular uptake of DOX in SCCVII cells compared to conventional radiopaque liposomes, likely due to clathrin-mediated endocytosis. Additionally, pH-dependent DOX release and reduced IPD leakage were observed. In vivo studies using SCCVII tumor-xenografted mice showed that RHLs exhibited improved CT contrast efficiency and anti-tumor efficacy, along with systemic biocompatibility, attributed to enhanced tumor-targeting properties. These findings suggest that the RHL system could serve as a promising nano-platform for tumor theranostics.

  View details for DOI 10.1016/j.biopha.2025.117822

  View details for PubMedID 39805193

• Gelatin nanofibers coated with hyaluronic acid as a mesenchymal stromal cell scaffold for corneal regeneration. International journal of pharmaceutics da Silva, G. R., Song, E., Chen, K. M., Chen, F., Jiang, L., Kim, H., Kang, N. W., Myung, D. 2024: 125009

  Abstract

  Electrospun gelatin nanofibers coated with hyaluronic acid (GelNF-HA) were synthesized as a scaffold for delivering human corneal mesenchymal stromal cells (C-MSCs) directly to deep corneal injuries. Aligned GelNFs were produced by electrospinning, crosslinked using vapor of glutaraldehyde, coated with HA, and crosslinked with EDC/NHS. The GelNF-HA was characterized by SEM, mechanical, and optical properties. It was then investigated as a substrate for C-MSC proliferation and migration in vitro and in a rabbit cornea culture model. The expression of α-smooth muscle actin (α-SMA) was determined in the ex vivo model. SEM showed that the GelNF-HA scaffold was composed of aligned GelNFs with 75 % of the fibers oriented against the same angle. It exhibited a Young's modulus of 1.66 ± 0.59 MPa and approximately 93 % transmittance of visible light. The GelNF-HA membranes supported C-MSC proliferation in vitro. In a scratch migration assay, it facilitated complete wound closure after 48 h in culture. C-MSC-laden GelNF-HA scaffolds supported corneal wound healing in an ex vivo model as well, expressing a lower percentage of stromal α-SMA compared to both the no-treatment keratectomy-only and C-MSC groups (p < 0.05). The C-MSC-supportive GelNF-HA scaffolds hold therapeutic potential for stromal regeneration in the treatment of deep corneal defects.

  View details for DOI 10.1016/j.ijpharm.2024.125009

  View details for PubMedID 39613275

• Photoactivated growth factor release from bio-orthogonally crosslinked hydrogels for the regeneration of corneal defects. Bioactive materials Kang, N., Seo, Y. A., Jackson, K. J., Jang, K., Song, E., Han, U., Chen, F., Heilshorn, S. C., Myung, D. 2024; 40: 417-429

  Abstract

  In situ-forming hydrogels are an attractive option for corneal regeneration, and the delivery of growth factors from such constructs have the potential to improve re-epithelialization and stromal remodeling. However, challenges persist in controlling the release of therapeutic molecules from hydrogels. Here, an in situ-forming bio-orthogonally crosslinked hydrogel containing growth factors tethered via photocleavable linkages (PC-HACol hydrogel) was developed to accelerate corneal regeneration. Epidermal growth factor (EGF) was conjugated to the hydrogel backbone through photo-cleavable (PC) spacer arms and was released when exposed to mild intensity ultraviolet (UV) light (2-5mW/cm2, 365nm). The PC-HACol hydrogel rapidly gelled within a few minutes when applied to corneal defects, with excellent transparency and biocompatibility. After subsequent exposure to UV irradiation, the hydrogel promoted the proliferation and migration of corneal epithelial cells in vitro. The rate of re-epithelialization was positively correlated to the frequency of irradiation, verified through ex vivo rabbit cornea organ culture studies. In an in vivo rat corneal wound healing study, the PC-HACol hydrogel exposed to UV light significantly promoted re-epithelialization, the remodeling of stromal layers, and exhibited significant anti-scarring effects, with minimal alpha-SMA and robust ALDH3A1 expression. Normal differentiation of the regenerated epithelia after healing was evaluated by expression of the corneal epithelial biomarker, CK12. The remodeled cornea exhibited full recovery of corneal thickness and layer number without hyperplasia of the epithelium.

  View details for DOI 10.1016/j.bioactmat.2024.05.045

  View details for PubMedID 39022184

• In Situ-Forming, Bioorthogonally Cross-linked, Nanocluster-Reinforced Hydrogel for the Regeneration of Corneal Defects. ACS nano Kang, N. W., Jang, K., Song, E., Han, U., Seo, Y. A., Chen, F., Wungcharoen, T., Heilshorn, S. C., Myung, D. 2024

  Abstract

  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.

  View details for DOI 10.1021/acsnano.4c02345

  View details for PubMedID 39106436

• Verteporfin Restores Corneal Transparency after Injury Liu, W. W., Chen, F., Wungcharoen, T., Kang, N., Garcia, J., Basco, C., Seo, Y., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001313316208346