David Myung, MD, PhD

All Publications

• In situ-forming hyaluronic acid hydrogel through visible light-induced thiolene reaction REACTIVE & FUNCTIONAL POLYMERS Lee, H., Fernandes-Cunha, G. M., Myung, D. 2018; 131: 29–35

  View details for DOI 10.1016/j.reactfunctpolym.2018.06.010

  View details for Web of Science ID 000448225200004

• Bio-Orthogonally Crosslinked, In Situ Forming Corneal Stromal Tissue Substitute. Advanced healthcare materials Lee, H. J., Fernandes-Cunha, G. M., Na, K., Hull, S. M., Myung, D. 2018: e1800560

  Abstract

  In this study, an in situ forming corneal stromal substitute based on collagen type I crosslinked by bio-orthogonal strain-promoted azide-alkyne cycloaddition (SPAAC) is presented. The crosslinked collagen gel has greater transparency compared to non-crosslinked collagen gels. The mechanical properties of the gels are controlled by changing functional group ratios and conjugated collagen concentrations. Higher concentrations of conjugated collagen yield enhances mechanical properties, where the storage modulus increases from 42.39 ± 8.95 to 112.03 ± 3.94 Pa after SPAAC crosslinking. Encapsulated corneal keratocytes grow within the SPAAC-crosslinked gels and corneal keratinocytes are supported on top of the gel surfaces. SPAAC-crosslinked gels support more favorable and stable keratinocyte morphology on their surface compared to non-crosslinked gels likely as a result of more optimal substrate stiffness, gel integrity, and resistance to degradation. SPAAC-crosslinked collagen gels with and without encapsulated keratocytes applied to rabbit corneas in an organ culture model after keratectomy exhibit surface epithelialization with multilayered morphology. The novel in situ forming gel is a promising candidate for lamellar and defect reconstruction of corneal stromal tissue.

  View details for DOI 10.1002/adhm.201800560

  View details for PubMedID 30106514

• Immobilization of growth factors to collagen surfaces using visible light. Biomacromolecules Fernandes Cunha, G. M., Lee, H. J., Kumar, A., Kreymerman, A., Heilshorn, S. C., Myung, D. 2017

  Abstract

  In the treatment of traumatic injuries, burns, and ulcers of the eye, inadequate epithelial tissue healing remains a major challenge. Wound healing is a complex process involving the temporal and spatial interplay between cells and their extracellular milieu. It can be impaired by a variety of causes including infection, poor circulation, loss of critical cells and/or proteins, and a deficiency in normal neural signaling (e.g. neurotrophic ulcers). Ocular anatomy is particularly vulnerable to lasting morbidity from delayed healing, whether it be scarring or perforation of the cornea, destruction of the conjunctival mucous membrane, or cicatricial changes to the eyelids and surrounding skin. Therefore, there is a major clinical need for new modalities for controlling and accelerating wound healing, particularly in the eye. Collagen matrices have long been explored as scaffolds to support cell growth as both two-dimensional coatings and substrates, as well as three-dimensional matrices. Meanwhile, the immobilization of growth factors to various substrates has also been extensively studied as a way to promote enhanced cellular adhesion and proliferation. Herein we present a new strategy for photochemically immobilizing growth factors to collagen using riboflavin as a photosensitizer and exposure to visible light (~458 nm). epidermal growth factor (EGF) was successfully bound to collagen-coated surfaces as well as directly to endogenous collagen from porcine corneas. The initial concentration of riboflavin and EGF, as well as the blue light exposure time, were keys to the successful binding of growth factor to these surfaces. The photocrosslinking reaction increased EGF residence time on collagen surfaces over seven days. EGF activity was maintained after the photocrosslinking reaction with a short duration of pulsed blue light exposure time. Bound EGF accelerated in vitro corneal epithelial cell proliferation and migration and maintained normal cell phenotype. Additionally, the treated surfaces were cytocompatible, and the photocrosslinking reaction was proven to be safe, preserving nearly 100% cell viability. These results suggest that this general approach is safe and versatile may be used for targeting and immobilizing bioactive factors onto collagen matrices in a variety of applications, including in the presence of live, seeded cells or in vivo onto endogenous extracellular matrix collagen.

  View details for DOI 10.1021/acs.biomac.7b00838

  View details for PubMedID 28799757

• Clinical Application of a Smartphone-Based Ophthalmic Camera Adapter in Under-Resourced Settings in Nepal Journal of Mobile Technology in Medicine Mercado, C., Welling, J., Oliva, M., Li, J., Gurung, R., Ruit, S., Tabin, G., Chang, D., Thapa, S., Myung, D. 2017; 6 (3): 34-42

  View details for DOI 10.7309/jmtm.6.3.6

• Tethering Growth Factors to Collagen Surfaces Using Copper-free Click Chemistry: Surface Characterization and In Vitro Biological Response. ACS applied materials & interfaces Lee, H. J., Fernandes-Cunha, G., Putra, I., Koh, W. G., Myung, D. 2017

  Abstract

  Surface modifications with tethered growth factors have mainly been applied to synthetic polymeric biomaterials in well-controlled, acellular settings, followed by seeding with cells. The known bio-orthogonality of copper-free click chemistry provides an opportunity to not only use it in vitro to create scaffolds or pro-migratory tracks in the presence of living cells, but also potentially apply it to living tissues directly as a coupling modality in situ. In this study, we studied the chemical coupling of growth factors to collagen using biocompatible copper-free click chemistry and its effect on the enhancement of growth factor activity in vitro. We verified the characteristics of modified epidermal growth factor (EGF) using mass spectrometry and EGF/EGF receptor binding assay, and chemical immobilization of EGF on collagen was also evaluated by copper-free click chemistry using surface x-ray photoelectron spectroscopy (XPS), surface plasmon resonance (SPR) spectroscopy, and enzyme-linked immunosorbent assay (ELISA). We found that the anchoring was non-cytotoxic, biocompatible, and sufficiently rapid for clinical application. Moreover, the surface-immobilized EGF has significant effects on epithelial cell attachment and proliferation. Our results demonstrate the possibility of copper-free click chemistry as a tool for covalent bonding of growth factors to extracellular matrix collagen and the potential effectiveness of immobilized EGF in this setting. This approach is a novel and potentially clinically useful application of copper-free click chemistry as a way of directly anchoring growth factors to collagen and foster epithelial wound healing.

  View details for DOI 10.1021/acsami.7b05262

  View details for PubMedID 28598594

• Training time and quality of smartphone-based anterior segment screening in rural India. Clinical ophthalmology (Auckland, N.Z.) Ludwig, C. A., Newsom, M. R., Jais, A., Myung, D. J., Murthy, S. I., Chang, R. T. 2017; 11: 1301–7

  Abstract

  We aimed at evaluating the ability of individuals without ophthalmologic training to quickly capture high-quality images of the cornea by using a smartphone and low-cost anterior segment imaging adapter (the "EyeGo" prototype).Seven volunteers photographed 1,502 anterior segments from 751 high school students in Varni, India, by using an iPhone 5S with an attached EyeGo adapter. Primary outcome measures were median photograph quality of the cornea and anterior segment of the eye (validated Fundus Photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department [FOTO-ED] study; 1-5 scale; 5, best) and the time required to take each photograph. Volunteers were surveyed on their familiarity with using a smartphone (1-5 scale; 5, very comfortable) and comfort in assessing problems with the eye (1-5 scale; 5, very comfortable). Binomial logistic regression was performed using image quality (low quality: <4; high quality: ≥4) as the dependent variable and age, comfort using a smartphone, and comfort in assessing problems with the eye as independent variables.Six of the seven volunteers captured high-quality (median ≥4/5) images with a median time of ≤25 seconds per eye for all the eyes screened. Four of the seven volunteers demonstrated significant reductions in time to acquire photographs (P1=0.01, P5=0.01, P6=0.01, and P7=0.01), and three of the seven volunteers demonstrated significant improvements in the quality of photographs between the first 100 and last 100 eyes screened (P1<0.001, P2<0.001, and P6<0.01). Self-reported comfort using a smartphone (odds ratio [OR] =1.25; 95% CI =1.13 to 1.39) and self-reported comfort diagnosing eye conditions (OR =1.17; 95% CI =1.07 to 1.29) were significantly associated with an ability to take a high-quality image (≥4/5). There was a nonsignificant association between younger age and ability to take a high-quality image.Individuals without ophthalmic training were able to quickly capture a high-quality magnified view of the anterior segment of the eye by using a smartphone with an attached imaging adapter.

  View details for DOI 10.2147/OPTH.S134656

  View details for PubMedID 28761328

  View details for PubMedCentralID PMC5522819

• SMARTPHONE-BASED DILATED FUNDUS PHOTOGRAPHY AND NEAR VISUAL ACUITY TESTING AS INEXPENSIVE SCREENING TOOLS TO DETECT REFERRAL WARRANTED DIABETIC EYE DISEASE RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Toy, B. C., Myung, D. J., He, L., Pan, C. K., Chang, R. T., Polkinhorne, A., Merrell, D., Foster, D., Blumenkranz, M. S. 2016; 36 (5): 1000-1008

  Abstract

  To compare clinical assessment of diabetic eye disease by standard dilated examination with data gathered using a smartphone-based store-and-forward teleophthalmology platform.100 eyes of 50 adult patients with diabetes from a health care safety-net ophthalmology clinic. All patients underwent comprehensive ophthalmic examination. Concurrently, a smartphone was used to estimate near visual acuity and capture anterior and dilated posterior segment photographs, which underwent masked, standardized review. Quantitative comparison of clinic and smartphone-based data using descriptive, kappa, Bland-Altman, and receiver operating characteristic analyses was performed.Smartphone visual acuity was successfully measured in all eyes. Anterior and posterior segment photography was of sufficient quality to grade in 96 and 98 eyes, respectively. There was good correlation between clinical Snellen and smartphone visual acuity measurements (rho = 0.91). Smartphone-acquired fundus photographs demonstrated 91% sensitivity and 99% specificity to detect moderate nonproliferative and worse diabetic retinopathy, with good agreement between clinic and photograph grades (kappa = 0.91 ± 0.1, P < 0.001; AUROC = 0.97, 95% confidence interval, 0.93-1).The authors report a smartphone-based telemedicine system that demonstrated sensitivity and specificity to detect referral-warranted diabetic eye disease as a proof-of-concept. Additional studies are warranted to evaluate this approach to expanding screening for diabetic retinopathy.

  View details for Web of Science ID 000375482100029

  View details for PubMedID 26807627

• A novel smartphone ophthalmic imaging adapter: User feasibility studies in Hyderabad, India INDIAN JOURNAL OF OPHTHALMOLOGY Ludwig, C. A., Murthy, S. I., Pappuru, R. R., Jais, A., Myung, D. J., Chang, R. T. 2016; 64 (3): 191-200

  Abstract

  To evaluate the ability of ancillary health staff to use a novel smartphone imaging adapter system (EyeGo, now known as Paxos Scope) to capture images of sufficient quality to exclude emergent eye findings. Secondary aims were to assess user and patient experiences during image acquisition, interuser reproducibility, and subjective image quality.The system captures images using a macro lens and an indirect ophthalmoscopy lens coupled with an iPhone 5S. We conducted a prospective cohort study of 229 consecutive patients presenting to L. V. Prasad Eye Institute, Hyderabad, India. Primary outcome measure was mean photographic quality (FOTO-ED study 1-5 scale, 5 best). 210 patients and eight users completed surveys assessing comfort and ease of use. For 46 patients, two users imaged the same patient's eyes sequentially. For 182 patients, photos taken with the EyeGo system were compared to images taken by existing clinic cameras: a BX 900 slit-lamp with a Canon EOS 40D Digital Camera and an FF 450 plus Fundus Camera with VISUPAC™ Digital Imaging System. Images were graded post hoc by a reviewer blinded to diagnosis.Nine users acquired 719 useable images and 253 videos of 229 patients. Mean image quality was ≥ 4.0/5.0 (able to exclude subtle findings) for all users. 8/8 users and 189/210 patients surveyed were comfortable with the EyeGo device on a 5-point Likert scale. For 21 patients imaged with the anterior adapter by two users, a weighted κ of 0.597 (95% confidence interval: 0.389-0.806) indicated moderate reproducibility. High level of agreement between EyeGo and existing clinic cameras (92.6% anterior, 84.4% posterior) was found.The novel, ophthalmic imaging system is easily learned by ancillary eye care providers, well tolerated by patients, and captures high-quality images of eye findings.

  View details for DOI 10.4103/0301-4738.181742

  View details for Web of Science ID 000376126800003

  View details for PubMedID 27146928

• Comparative In vitro Cytotoxicity of Artificial Tears JSM Ophthalmology Zhen, L., Myung, D., Yu, C. Q., Ta, C. N. 2015; 3 (1): 1-6
• Grafting of Cross-Linked Hydrogel Networks to Titanium Surfaces ACS APPLIED MATERIALS & INTERFACES Muir, B. V., Myung, D., Knoll, W., Frank, C. W. 2014; 6 (2): 958-966

  Abstract

  The performance of medical implants and devices is dependent on the biocompatibility of the interfacial region between tissue and the implant material. Polymeric hydrogels are attractive materials for use as biocompatible surface coatings for metal implants. In such systems, a factor that is critically important for the longevity of an implant is the formation of a robust bond between the hydrogel layer and the implant metal surface and the ability for this assembly to withstand physiological conditions. Here, we describe the grafting of cross-linked hydrogel networks to titanium surfaces using grit-blasting and subsequent chemical functionalization using a silane-based adhesion promoter. Metal surface characterization was carried out using profilometry, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) analysis. Hydrogel layers composed of poly(ethylene glycol)-dimethacrylate (PEG-DMA), poly(2-hydroxyethylmethacrylate) (PHEMA), or poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) semi-interpenetrating polymer networks (semi-IPNs) have been prepared. The mechanical properties of these hydrogel-metal assemblies have been characterized using lap-shear measurements, and the surface morphology was studied by SEM and EDX. We have shown that both high surface roughness and chemical functionalization are critical for adhesion of the hydrogel layer to the titanium substrate.

  View details for DOI 10.1021/am404361v

  View details for Web of Science ID 000330201900031

  View details for PubMedID 24364560

• Simple, Low-Cost Smartphone Adapter for Rapid, High Quality Ocular Anterior Segment Imaging: A Photo Diary Journal of Mobile Technology and Medicine Myung, D., Jais, A., He, L., Chang, R. T. 2014; 3 (1)
• 3D Printed Smartphone Indirect Lens Adapter for Rapid, High Quality Retinal Imaging Journal of Mobile Technology in Medicine Myung, D., Jais, A., He, L., Blumenkranz, M., Chang, R. 2014; 3 (1)
• Pupil Size and LASIK: A Review JOURNAL OF REFRACTIVE SURGERY Myung, D., Schallhorn, S., Manche, E. E. 2013; 29 (11): 734-?

  Abstract

  To provide a literature review on the evidence both for and against pupil size as an independent predictor of adverse visual outcomes after LASIK.Peer-reviewed publications on the effect of pupil size on LASIK outcomes since 2002 are reviewed. Particular attention was paid to the following attributes of each publication: type of study, number of patients or eyes, mean age, mean level of myopia, mean pupil size, testing conditions, ablation zone diameter, presence or absence of blend zones, and mean follow-up period.Among the 19 studies examined, none correlates a persistent relationship between pupil size and night vision complaints (NVCs) beyond 3 months when LASIK was performed with a 6.0-mm optical zone or larger ablation. The studies that did explicitly determine a correlation either included some or all patients with ablation zones smaller than 6.0 mm or did not specify ablation diameter at all. Among the studies that had drawn more mixed conclusions, the studies either covered short follow-up intervals (1 to 3 months) or showed a progressive improvement in NVCs over time in a relatively small patient cohort.As keratorefractive technology continues to evolve, the role of pupil size warrants further investigation; however, based on the literature reviewed herein, modern LASIK has negated the role of the low light pupil in predicting adverse visual outcomes after LASIK outside of the early postoperative period.

  View details for DOI 10.3928/1081597X-20131021-02

  View details for Web of Science ID 000329186600002

  View details for PubMedID 24203804

• In vivo biocompatibility of two PEG/PAA interpenetrating polymer networks as corneal inlays following deep stromal pocket implantation JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE Tan, X. W., Hartman, L., Tan, K. P., Poh, R., Myung, D., Zheng, L. L., Waters, D., Noolandi, J., Beuerman, R. W., Frank, C. W., Ta, C. N., Tan, D. T., Mehta, J. S. 2013; 24 (4): 967-977

  Abstract

  This study compared the effects of implanting two interpenetrating polymer networks (IPNs) into rabbit corneas. The first (Implant 1) was based on PEG-diacrylate, the second (Implant 2) was based on PEG-diacrylamide. There were inserted into deep stromal pockets created using a manual surgical technique for either 3 or 6 months. The implanted corneas were compared with normal and sham-operated corneas through slit lamp observation, anterior segment optical coherence tomography, in vivo confocal scanning and histological examination. Corneas with Implant 1 (based on PEG-diacrylate) developed diffuse haze, ulcers and opacities within 3 months, while corneas with Implant 2 (based on PEG-diacrylamide) remained clear at 6 months. They also exhibited normal numbers of epithelial cell layers, without any immune cell infiltration, inflammation, oedema or neovascularisation at post-operative 6 month. Morphological studies showed transient epithelial layer thinning over the hydrogel inserted area and elevated keratocyte activity at 3 months; however, the epithelium thickness and keratocyte morphology were improved at 6 months. Implant 2 exhibited superior in vivo biocompatibility and higher optical clarity than Implant 1. PEG-diacrylamide-based IPN hydrogel is therefore a potential candidate for corneal inlays to correct refractive error.

  View details for DOI 10.1007/s10856-012-4848-3

  View details for Web of Science ID 000318509100013

  View details for PubMedID 23354737

  View details for PubMedCentralID PMC3620449

• Biocompatibility of poly(ethylene glycol)/poly(acrylic acid) interpenetrating polymer network hydrogel particles in RAW 264.7 macrophage and MG-63 osteoblast cell lines. Journal of biomedical materials research. Part A Yim, E. S., Zhao, B., Myung, D., Kourtis, L. C., Frank, C. W., Carter, D., Smith, R. L., Goodman, S. B. 2009; 91 (3): 894-902

  Abstract

  Hydrogel polymers comprise a novel category of synthetic materials being investigated for use in cartilage replacement. One candidate compound, a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network (IPN), was developed for use in corneal prostheses and was recently engineered for potential orthopedic use. The current study examined the effects of particles of this compound on two cell lines (MG-63 osteoblast-like cells and RAW 264.7 macrophages) over a 48-h time course. To mimic the effects of wear debris, particles of the compound were generated and introduced to the cells. In the MG-63 cell line, the particles had no significant effect on cell viability measured by PicoGreen assay and trypan blue exclusion. In contrast, a significant decrease in cell viability was detected in the Raw 264.7 macrophage cells at the final timepoint with the highest concentration of hydrogel (3.0% v:v). A concentration- and time-dependent increase in TNF-alpha release characteristic of other known biocompatible materials was also detected in RAW 264.7 cells, but nitric oxide and interleukin (IL)-1beta showed no response. In addition, the MG-63 cell line demonstrated no IL-6 response. Particles of the PEG/PAA IPN thus seem to stimulate biological responses similar to those in other biocompatible materials.

  View details for DOI 10.1002/jbm.a.32311

  View details for PubMedID 19072924

• Bioactive interpenetrating polymer network hydrogels that support corneal epithelial wound healing. Journal of biomedical materials research. Part A Myung, D., Farooqui, N., Zheng, L. L., Koh, W., Gupta, S., Bakri, A., Noolandi, J., Cochran, J. R., Frank, C. W., Ta, C. N. 2009; 90 (1): 70-81

  Abstract

  The development and characterization of collagen-coupled poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network hydrogels is described. Quantitative amino acid analysis and FITC-labeling of collagen were used to determine the amount and distribution of collagen on the surface of the hydrogels. The bioactivity of the coupled collagen was detected by a conformation-specific antibody and was found to vary with the concentration of collagen reacted to the photochemically functionalized hydrogel surfaces. A wound healing assay based on an organ culture model demonstrated that this bioactive surface supports epithelial wound closure over the hydrogel but at a decreased rate relative to sham wounds. Implantation of the hydrogel into the corneas of live rabbits demonstrated that epithelial cell migration is supported by the material, although the rate of migration and morphology of the epithelium were not normal. The results from the study will be used as a guide toward the optimization of bioactive hydrogels with promise in corneal implant applications such as a corneal onlay and an artificial cornea.

  View details for DOI 10.1002/jbm.a.32056

  View details for PubMedID 18481785

  View details for PubMedCentralID PMC2856598

• Progress in the development of interpenetrating polymer network hydrogels POLYMERS FOR ADVANCED TECHNOLOGIES Myung, D., Waters, D., Wiseman, M., Duhamel, P., Noolandi, J., Ta, C. N., Frank, C. W. 2008; 19 (6): 647-657

  Abstract

  Interpenetrating polymer networks (IPNs) have been the subject of extensive study since their advent in the 1960s. Hydrogel IPN systems have garnered significant attention in the last two decades due to their usefulness in biomedical applications. Of particular interest are the mechanical enhancements observed in "double network" IPN systems which exhibit nonlinear increases in fracture properties despite being composed of otherwise weak polymers. We have built upon pioneering work in this field as well as in responsive IPN systems to develop an IPN system based on end-linked poly-(ethylene glycol) (PEG) and loosely crosslinked poly(acrylic acid) (PAA) with hydrogen bond-reinforced strain-hardening behavior in water and high initial Young's moduli under physiologic buffer conditions through osmotically induced pre-stress. Uniaxial tensile tests and equilibrium swelling measurements were used to study PEG/PAA IPN hydrogels having second networks prepared with varying crosslinking and photoinitiator content, pH, solids content, and comonomers. Studies involving the addition of non-ionic comonomers and neutralization of the second network showed that template polymerization appears to be important in the formation of mechanically enhanced IPNs.

  View details for DOI 10.1002/pat.1134

  View details for Web of Science ID 000257014100025

  View details for PubMedCentralID PMC2745247

• Development of hydrogel-based keratoprostheses: A materials perspective 234th National Meeting of the American-Chemical-Society Myung, D., Duhamel, P., Cochran, J. R., Noolandi, J., Ta, C. N., Frank, C. W. WILEY-BLACKWELL. 2008: 735–41

  Abstract

  Research and development of artificial corneas (keratoprostheses) in recent years have evolved from the use of rigid hydrophobic materials such as plastics and rubbers to hydrophilic, water-swollen hydrogels engineered to support not only peripheral tissue integration but also glucose diffusion and surface epithelialization. The advent of the AlphaCor core-and-skirt hydrogel keratoprosthesis has paved the way for a host of new approaches based on hydrogels and other soft materials that encompass a variety of materials preparation strategies, from synthetic homopolymers and copolymers to collagen-based bio-copolymers and, finally, interpenetrating polymer networks. Each approach represents a unique strategy toward the same goal: to develop a new hydrogel that mimics the important properties of natural donor corneas. We provide a critical review of these approaches from a materials perspective and discuss recent experimental results. While formidable technical hurdles still need to be overcome, the rapid progress that has been made by investigators with these approaches is indicative that a synthetic donor cornea capable of surface epithelialization is now closer to becoming a clinical reality.

  View details for DOI 10.1021/bp070476n

  View details for Web of Science ID 000256593300033

  View details for PubMedID 18422366

  View details for PubMedCentralID PMC2743969

• Glucose-permeable interpenetrating polymer network hydrogels for corneal implant applications: A pilot study CURRENT EYE RESEARCH Myung, D., Farooqui, N., Waters, D., Schaber, S., Koh, W., Carrasco, M., Noolandi, J., Frank, C. W., Ta, C. N. 2008; 33 (1): 29-43

  Abstract

  Epithelialization of a keratoprosthesis requires that the implant material be sufficiently permeable to glucose. We have developed a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network (IPN) hydrogel that can provide adequate passage of glucose from the aqueous humor to the epithelium in vivo. A series of PEG/PAA IPNs with varying PEG macromonomer molecular weights were synthesized and evaluated through swelling studies to determine their water content and diffusion experiments to assess their permeability to glucose. One of the PEG/PAA hydrogels prepared in this study had a glucose diffusion coefficient nearly identical to that of the human cornea (approximately 2.5 x 10(-6) cm(2)/sec). When implanted intrastromally in rabbit corneas, this hydrogel was retained and well-tolerated in 9 out of 10 cases for a period of 14 days. The retained hydrogels stayed optically clear and the epithelium remained intact and multilayered, indicating that the material facilitated glucose transport from the aqueous humor to the anterior part of the eye. The results from these experiments indicate that PEG/PAA hydrogels are promising candidates for corneal implant applications such as keratoprostheses and intracorneal lenses, and that the PEG/PAA IPN system in general is useful for creating permeable substrates for ophthalmic and other biomedical applications.

  View details for DOI 10.1080/02713680701793930

  View details for Web of Science ID 000252582500005

  View details for PubMedID 18214741

• Design and fabrication of an artificial cornea based on a photolithographically patterned hydrogel construct BIOMEDICAL MICRODEVICES Myung, D., Koh, W., Bakri, A., Zhang, F., Marshall, A., Ko, J., Noolandi, J., Carrasco, M., Cochran, J. R., Frank, C. W., Ta, C. N. 2007; 9 (6): 911-922

  Abstract

  We describe the design and fabrication of an artificial cornea based on a photolithographically patterned hydrogel construct, and demonstrate the adhesion of corneal epithelial and fibroblast cells to its central and peripheral components, respectively. The design consists of a central "core" optical component and a peripheral tissue-integrable "skirt." The core is composed of a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) double-network with high strength, high water content, and collagen type I tethered to its surface. Interpenetrating the periphery of the core is a microperforated, but resilient poly(hydroxyethyl acrylate) (PHEA) hydrogel skirt that is also surface-modified with collagen type I. The well-defined microperforations in the peripheral component were created by photolithography using a mask with radially arranged chrome discs. Surface modification of both the core and skirt elements was accomplished through the use of a photoreactive, heterobifunctional crosslinker. Primary corneal epithelial cells were cultured onto modified and unmodified PEG/PAA hydrogels to evaluate whether the central optic material could support epithelialization. Primary corneal fibroblasts were seeded onto the PHEA hydrogels to evaluate whether the peripheral skirt material could support the adhesion of corneal stromal cells. Cell growth in both cases was shown to be contingent on the covalent tethering of collagen. Successful demonstration of cell growth on the two engineered components was followed by fabrication of core-skirt constructs in which the central optic and peripheral skirt were synthesized in sequence and joined by an interpenetrating diffusion zone.

  View details for DOI 10.1007/s10544-006-9040-4

  View details for Web of Science ID 000250462200017

  View details for PubMedID 17237989

• Prospective randomized comparison of 1-day versus 3-day application of topical levofloxacin in eliminating conjunctival flora. European journal of ophthalmology Ta, C. N., Sinnar, S., He, L., Myung, D., Mino De Kaspar, H. 2007; 17 (1): 689-695

  Abstract

  To compare efficacy of a 1-day versus 3-ayapplication of topical levofloxacin in reducing ocular surface bacteria.In this prospective randomized controlled trial, 100 volunteer patients (50 per group) were assigned to receive topical 0.5% levofloxacin four times daily for 1 day or 3 days. Conjunctival cultures were obtained prior to (T0) and after the application of antibiotics (T1). Additionally, all patients received topical levofloxacin at 5-minute intervals for three applications (T2), followed by two drops of topical 5% povidone-iodine (T3). Conjunctival cultures were obtained at timepoints T2 and T3.A 1-day application of topical levofloxacin significantly reduced (p = 0.0004) the number of eyes with positive conjunctival cultures from 41 eyes (82%) to 23 eyes (46%). Similarly, a 3-day application significantly reduced (p = 0.0001) the positive culture rate from 37 eyes (74%) to 17 eyes (34%). Two drops of povidone-iodine further reduced the positive culture rate for both groups to 20% (10 eyes for each group). There was no significant difference in positive culture rate between the 1-day and 3-day groups at T0 (p = 0.4689), T1 (p = 0.3074), T2 (p = 0.6706), or T3 (p = 1.000).The application of topical 0.5% levofloxacin for 1 or 3 days significantly reduced the number of eyes with positive conjunctival cultures. The addition of 5% povidone-iodine further eliminated bacteria from the conjunctiva. The application of levofloxacin for 1 day appears to be as effective as a 3-day application.

  View details for DOI 10.5301/EJO.2008.3555

  View details for PubMedID 28221506

• Histological processing of pH-sensitive hydrogels used in corneal implant applications JOURNAL OF HISTOTECHNOLOGY Farooqui, N., Myung, D., Koh, W., Masek, M., Dalal, R., Carrasco, M. R., Noolandi, J., Frank, C. W., Ta, C. N. 2007; 30 (3): 157-163

  View details for Web of Science ID 000258533600003

• Biomimetic strain hardening in interpenetrating polymer network hydrogels POLYMER Myung, D., Koh, W., Ko, J., Hu, Y., Carrasco, M., Noolandi, J., Ta, C. N., Frank, C. W. 2007; 48 (18): 5376-5387

  View details for DOI 10.1016/j.polymer.2007.06.070

  View details for Web of Science ID 000249712800021

• Glucose permeability of human, bovine, and porcine corneas in vitro OPHTHALMIC RESEARCH Myung, D., Derr, K., Huie, P., Noolandi, J., Ta, K. P., Ta, C. N. 2006; 38 (3): 158-163

  Abstract

  To measure glucose flux across human, bovine, and porcine corneas and to determine the diffusion coefficient of each type of cornea.Diffusion of glucose across human (n = 8), bovine (n = 7), and pig corneas (n = 8) was measured using a modified blind well chamber apparatus (Boyden chamber). Dialysis membranes (n = 7) and nonporous Mylar membranes (n = 7) were used as positive and negative controls, respectively. Glucose concentrations were measured at 30-min intervals with a commercially available glucose meter.The diffusion of glucose through corneas in vitro was calculated by a simple Fickian diffusion model. The diffusion coefficient of glucose is highest for the human cornea (D(HC) = 3.0 +/- 0.2 x 10(-6) cm(2)/s) followed by porcine corneas (D(PC) = 1.8 +/- 0.6 x 10(-6) cm(2)/s) and bovine corneas (D(BC) = 1.6 +/- 0.1 x 10(-6) cm(2)/s) (p < 0.05). The diffusion coefficients of all tested corneas were significantly higher (p < 0.05) than that of dialysis membrane (D(DM) = 3.4 +/- 0.2 x 10(-7) cm(2)/s).The glucose diffusion coefficients of human, bovine, and porcine corneas are on the order of 10(-6). Human corneas have higher permeability to glucose than either porcine or bovine corneas.

  View details for DOI 10.1159/000090726

  View details for Web of Science ID 000238052500005

  View details for PubMedID 16401912