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Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses. Wearable electronics have been utilized for a number of applications including for ocular use, although their use has been limited to a single function. Here, the authors developed a multifunctional contact lens with wireless electronics for measurement of glucose and intraocular pressure.

Corneal transplantation is a typical surgical procedure for severe corneal diseases. However, the waiting time for a donor cornea has gradually increased due to a decrease in supply caused by an aging population and increased cases of laser-based surgeries. Artificial corneas were developed to meet the increase in demand; however, these approaches have suffered from material deterioration resulted by the limited tissue integration. Here, we introduce a cornea-derived decellularized extracellular matrix (Co-dECM) as a bioink for corneal regeneration. The developed Co-dECM bioink had similar quantitative measurement results for collagen and GAGs compared with that of the native cornea and also had the proper transparency for vision. The differentiation potential of human turbinate-derived mesenchymal stem cells (hTMSCs) to a keratocyte lineage was only observed in the Co-dECM group. Moreover, the developed bioink did not have any cytotoxic effect on encapsulated cells for three-dimensional (3D) culture and has great biocompatibility evident by the xeno-implantation of the Co-dECM gel into mice and rabbits for two and one month, respectively. An in vivo safety similar to clinical-grade collagen was seen with the Co-dECM, which helped to maintain the keratocyte-specific characteristics in vivo, compared with collagen. Taken together, the Co-dECM bioink has the potential to be used in various types of corneal diseases based on its corneal-specific ability and design flexibility through 3D cell printing technology.

In penetrating keratoplasty (PKP), the proper corneal suture placement is very important for successful transplantation and restoring functional vision. Generating sutures with accurate depth is difficult for the surgeon because of the tissue’s softness, lack of depth information, and hand tremors. In this paper, an automatic cornea grasping device is proposed, which detects when the device reaches the target suture depth. When the device reaches the target depth, the device rapidly grasps the cornea to prevent error induced by human hand tremors. In the paper, the performance of the proposed sensor, the actuator, and the device are experimentally verified with ex vivo experiment. The result showed that the proposed device could enhance the accuracy and precision of the corneal suture depth.

Purpose Platelet-rich plasma (PRP) harbors high concentrations of growth factors related to the promotion of wound healing. We evaluated the efficacy of PRP eyedrops in the treatment of persistent epithelial defects (PEDs). Methods Autologous PRP and autologous serum (AS) were prepared from whole blood. The concentrations of transforming growth factor (TGF)-β1, TGF-β2, epidermal growth factor (EGF), vitamin A and fibronectin in the PRP and AS were analyzed and compared. The corneal epithelial healing efficacy of PRP was compared with that of AS in patients with PED induced by post-infectious inflammation. Results The concentrations of TGF-β1, TGF-β2, EGF, vitamin A and fibronectin in the PRP and AS were not statistically different. However, the concentrations of EGF in the PRP were significantly greater than in the AS. AS was used in 17 and PRP in 11 eyes of 28 patients. The healing rates of the corneal epithelia of the PRP-treated eyes were significantly higher than those treated with AS. Conclusions The PRP was effective in the treatment of PEDs. This may be attributable to its high concentration of platelet-contained growth factors, most notably EGF. PRP could be an effective, novel treatment option for chronic ocular surface disease.

Mesenchymal stem cells could potentially be used in the clinical treatment of muscle disorders and muscle regeneration. Adipose-derived stem cells (ADSCs) can be easily isolated from adipose tissue, as opposed to stem cells of other tissues. We believe that cell therapy using ADSCs could be applied to muscle disorders in horses and other species. We sought to improve the myogenic differentiation potential of equine ADSCs (eqADSCs) using a MyoD lentiviral vector. MyoD lentiviruses were transduced into eqADSCs and selected using puromycin. Cells were cultured in differentiation media containing 5% horse serum, and after 5 days the MyoD-transduced cells differentiated into myogenic cells (MyoD-eqADSCs). Using green fluorescent protein (GFP), MyoD-eqADSCs were purified and transplanted into the tibialis anterior muscles of mice after they were injured with the myotoxin notexin. The mice were sacrificed to examine any regeneration in the tibialis anterior muscle 4 weeks after the MyoD-eqADSCs were injected. The MyoD-eqADSCs cultured in growth media expressed murine and equine MyoD; however, they did not express late differentiation markers such as myogenin (MYOG). When cells were grown in differentiation media, the expression of MYOG was clearly observed. According to our reverse transcription polymerase chain reaction and immunocytochemistry results, MyoD-eqADSCs expressed terminal myogenic phase genes, such as those encoding dystrophin, myosin heavy chain, and troponin I. The MyoD-eqADSCs fused to each other, and the formation of myotube-like cells from myoblasts in differentiation media occurred between days 5 and 14 postplating. In mice, we observed GFP-positive myofibers, which had differentiated from the injected MyoD-eqADSCs. Our approaches improved the myogenic differentiation of eqADSCs through the forced expression of murine MyoD. Our findings suggest that limitations in the treatment of equine muscle disorders could be overcome using ADSCs.

Purpose We report the clinical efficacy of sequential applications of 0.3% and 0.15% unpreserved hyaluronic acid (HA) for the treatment of dry eye disease (DED). Study design Randomized clinical trial. Methods Patients over 19 years of age with DED level 2 or higher, corneal fluorescein staining (CFS) score > 1, and tear break-up time (TBUT) < 10 s were included. Seventy-six patients were randomly assigned to the 0.15% HA group, 0.3% HA group, or combination group. Each group applied two drops of 0.15% or 0.3% HA, or a single drop of both 0.3% and 0.15% HA. Patients were evaluated using the ocular surface disease index (OSDI), CFS and conjunctival fluorescein stain score, TBUT, and blurring/discomfort after application at baseline, 4 weeks, and 8 weeks. Results The combination group had the greatest improvement in CFS score from baseline to 8 weeks, compared with the 0.15% and 0.3% HA group (p < 0.001). The combined CFS-OSDI responder rates of the combination group (CFS score = 0 and OSDI ≥ 50% improvement at 8 weeks) were significantly higher than those of the 0.15% and 0.3% groups (p = 0.037). At 4 and 8 weeks, blurring after application in both the 0.3% and combination groups was significantly higher than in the 0.15% group, despite no difference between the 0.3% and combination groups. There were no differences in CFS and conjunctival staining score, TBUT, or OSDI within the three groups at baseline, 4 weeks, and 8 weeks. Conclusions Sequential application of 0.3% and 0.15% HA improved symptoms/signs in moderate to severe DED patients.

Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called ‘personalized lag time’. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation. The correlation between tear glucose and blood glucose is still controversial. Here, the authors demonstrated the correlation between tear glucose and blood glucose in both animal models and human subjects using smart contact lenses.

Background: Osseogate is a novel drug delivery route through bone marrow involving a modified implant used as the drug delivery system. The purpose of this study was to evaluate the effects of individual drug physicochemical characteristics on the pharmacokinetic behavior when using the Osseogate as administration route.Methods: Implant-mediated drug delivery systems (IMDDS) were installed in a total of 18 rabbits. After complete healing, water-soluble metformin hydrochloride was administered to one group (n = 9) while poorly soluble dexamethasone was administered to the other group (n = 9). The release patterns of each group were monitored for two weeks by measuring the plasma concentration of each drug.Results: Both groups showed relative sustained release. However, metformin hydrochloride showed more rapid diffusion and early termination of drug release compared with dexamethasone.Conclusions: The physicochemical properties of drugs significantly affected the release pattern through Osseogate. Further research is required to achieve controlled delivery using this route.

Continuous detection of raised intraocular pressure (IOP) could benefit the monitoring of patients with glaucoma. Current contact lenses with embedded sensors for measuring IOP are rigid, bulky, partially block vision or are insufficiently sensitive. Here, we report the design and testing in volunteers of a soft and transparent contact lens for the quantitative monitoring of IOP in real time using a smartphone. The contact lens incorporates a strain sensor, a wireless antenna, capacitors, resistors, stretchable metal interconnects and an integrated circuit for wireless communication. In rabbits, the lens provided measurements that match those of a commercial tonometer. In ten human participants, the lens proved to be safe, and reliably provided accurate quantitative measurements of IOP without inducing inflammation. A soft and transparent contact lens can be used to wirelessly monitor intraocular pressure quantitatively in humans.

To measure needle insertion force and change in intraocular pressure (IOP) in real-time during intravitreal injection (IVI). The effects of needle size, insertion speed, and injection rate to IOP change were investigated. Needle insertion and fluid injection were performed on 90 porcine eyeballs using an automatic IVI device. The IVI conditions were divided according to needle sizes of 27-gauge (G), 30G, and 33G; insertion speeds of 1, 2, and 5 mm/s; and injection rates of 0.01, 0.02, and 0.05 mL/s. Insertion force and IOP were measured in real-time using a force sensor and a pressure transducer. The peak IOP was observed when the needle penetrated the sclera; the average IOP elevation was 96.3, 67.1, and 59.4 mmHg for 27G, 30G, and 33G needles, respectively. An increase in insertion speed caused IOP elevation at the moment of penetration, but this effect was reduced as needle size decreased: 109.8-85.9 mmHg in 27G for 5-1 mm/s (p = 0.0149) and 61.8-60.7 mmHg in 33G for 5-1 mm/s (p = 0.8979). Injection speed was also related to IOP elevation during the stage of drug injection: 16.65 and 11.78 mmHg for injection rates of 0.05 and 0.01 mL/s (p < 0.001). The presented data offers an understanding of IOP changes during each step of IVI. Slow needle insertion can reduce IOP elevation when using a 27G needle. Further, the injection rate must be kept low to avoid IOP elevations during the injection stage.