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Ya-Chun Chu,1,2,* Hsu-Wei Fang,2,3,* Yu-Yi Wu,1 Yu-Jun Tang,1 Erh-Hsuan Hsieh,1 YiZhou She,4 Che-Yi Chang,1 I-Chan Lin,5,6 Yin-Ju Chen,1,7– 9 Guei-Sheung Liu,1,10– 12 Ching-Li Tseng1,8,9,13 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 2Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei City, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan; 4School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 5Department of Ophthalmology, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan; 6Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; 7Department of Radiation Oncology, Taipei Medical University Hospital, Taipei City, Taiwan; 8International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 9Center for Precision Medicine and Translational Cancer Research, Taipei Medical University Hospital, Taipei City, Taiwan; 10Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia; 11Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia; 12Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia; 13Research Center of Biomedical Device, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Ching-Li Tseng, Tel +886 2 2736 1661 (ext. 5214), Email chingli@tmu.edu.twBackground: Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing through the cornea, resulting in vision loss or even blindness. The use of nanomedicine as an effective therapeutic formulation in ophthalmology has led to higher drug bioavailability and a slow drug release rate. In this research, we designed and explored the feasibility of a new nanomedicine, gp91 ds-tat (gp91) peptide-encapsulated gelatin nanoparticles (GNP-gp91), for inhibiting corneal angiogenesis.Methods: GNP-gp91 were prepared by a two-step desolvation method. The characterization and cytocompatibility of GNP-gp91 were analyzed. The inhibition effect of GNP-gp91 on HUVEC cell migration and tube formation was observed by an inverted microscope. The drug retention test in mouse cornea was observed by in vivo imaging system, fluorescence microscope, and DAPI/TAMRA staining. Finally, the therapeutic efficacy and evaluation of neovascularization-related factors were conducted through the in vivo corneal NV mice model via topical delivery.Results: The prepared GNP-gp91 had a nano-scale diameter (550.6 nm) with positive charge (21.7 mV) slow-release behavior (25%, 240hr). In vitro test revealed that GNP-gp91 enhanced the inhibition of cell migration and tube formation capacity via higher internalization of HUVEC. Topical administration (eyedrops) of the GNP-gp91 significantly prolongs the retention time (46%, 20 min) in the mouse cornea. In chemically burned corneal neovascularization models, corneal vessel area with a significant reduction in GNP-gp91 group (7.89%) was revealed when compared with PBS (33.99%) and gp91 (19.67%) treated groups via every two days dosing. Moreover, GNP-gp91 significantly reduced the concentration of Nox2, VEGF and MMP9 in NV’s cornea.Conclusion: The nanomedicine, GNP-gp91, was successfully synthesized for ophthalmological application. These data suggest that GNP-gp91 contained eyedrops that not only have a longer retention time on the cornea but also can treat mice corneal NV effectively delivered in a low dosing frequency, GNP-gp91 eyedrops provides an alternative strategy for clinical ocular disease treatment in the culture.Keywords: gp91 peptide, gelatin, nanoparticles, ocular retention, control release, corneal neovascularization, eye drops

Background: Cardiac discomfort has been reported periodically in COVID-19 vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Methods and Results: Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests and echocardiogram. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. After vaccination, 66 individuals (55.4 ± 17.4 years) developed cardiac discomfort, such as chest tightness, palpitations, dyspnea, and chest pain. All had normal serum levels of creatine phosphokinase, creatine kinase myocardial band, troponin, N-terminal pro b-type natriuretic peptide, platelets, and D-dimer. Left ventricular ejection fraction in the symptomatic group (71.41% ± 7.12%) and the control group (72.18% ± 5.11%) (p = 0.492) were normal. Use of 2D-STE presented global longitudinal strain (GLS) and global circumferential strain (GCS) were reduced in symptomatic group (17.86% ± 3.22% and 18.37% ± 5.22%) compared to control group (19.54% ± 2.18% and 20.73% ± 4.09%) (p = 0.001 and p = 0.028). Conclusion: COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable evaluation of subtle changes in myocardial function after vaccination.

Rationale: Corneal neovascularization (CoNV) is a severe complication of various types of corneal diseases, that leads to permanent visual impairment. Current treatments for CoNV, such as steroids or anti-vascular endothelial growth factor agents, are argued over their therapeutic efficacy and adverse effects. Here, we demonstrate that transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) plays an important role in the pathogenesis of CoNV. Methods: Angiogenic activities were assessed in ex vivo and in vitro models subjected to TAK1 inhibition by 5Z-7-oxozeaenol, a selective inhibitor of TAK1. RNA-Seq was used to examine pathways that could be potentially affected by TAK1 inhibition. A gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol was developed as the eyedrop to treat CoNV in a rodent model. Results: We showed that 5Z-7-oxozeaenol reduced angiogenic processes through impeding cell proliferation. Transcriptome analysis suggested 5Z-7-oxozeaenol principally suppresses cell cycle and DNA replication, thereby restraining cell proliferation. In addition, inhibition of TAK1 by 5Z-7-oxozeaenol blocked TNFα-mediated NFκB signalling, and its downstream genes related to angiogenesis and inflammation. 5Z-7-oxozeaenol also ameliorated pro-angiogenic activity, including endothelial migration and tube formation. Furthermore, topical administration of the gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol led to significantly greater suppression of CoNV in a mouse model compared to the free form of 5Z-7-oxozeaenol, likely due to extended retention of 5Z-7-oxozeaenol in the cornea. Conclusion: Our study shows the potential of TAK1 as a therapeutic target for pathological angiogenesis, and the gelatin nanoparticle coupled with 5Z-7-oxozeaenol as a promising new eyedrop administration model in treatment of CoNV.

Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.

Lung cancer has the highest mortality of any cancer worldwide, and cisplatin is a first-line chemotherapeutic agent for lung cancer treatment. Unfortunately, cisplatin resistance is a common cause of therapeutic failure. The ability to overcome chemoresistance is crucial to the effective treatment of lung cancer. Recently, epigallocatechin gallate (EGCG), a type of polyphenol extracted from tea, has been shown to suppress the rapid proliferation of cancer cells, including lung cancer. We tested whether nanoparticles (NPs) carrying a dual drug load, cisplatin and EGCG, could overcome chemoresistance to cisplatin, by working together to kill lung cancer cells. Self-assembling gelatin/EGCG nanoparticles (GE) were synthesized, and cisplatin was then incorporated, to construct a dual drug nanomedicine (EGCG/cisplatin-loaded gelatin nanoparticle, named as GE-Pt NP). The particle size and zeta potential were examined by dynamic light scattering (DLS). The morphological structure of GE-Pt NPs was observed by transmission electron microscopy (TEM). In vitro testing was performed using a human lung adenocarcinoma cell line (A549). A cytotoxicity examination was performed, using a WST-8 cell proliferation assay. Intracellular cisplatin content was quantified by inductively coupled plasma mass spectrometry (ICP-MS). In conclusion, we successfully prepared GE-Pt NPs, as spherical structures, approximately 75 nm in diameter, with a positive charge (+19.83±0.25 mV). The encapsulation rate of cisplatin in GE-Pt was about 63.7%, and the EGCG loading rate was around 89%. A relatively low concentration of GE-Pt NPs (EGCG 5 μg/mL : cisplatin 2 μg/mL) exhibited significant cytotoxicity, compared to cisplatin alone. The GE-Pt NPs are freely taken up by cells via endocytosis, raising the intracellular cisplatin concentration to a therapeutic level. We consider that combination therapy of cisplatin and EGCG in nanoparticles (GE-Pt NPs) may help overcome cisplatin resistance and could effectively be used in the treatment of lung cancer.

When a contact lens is in contact with the eyelid and the cornea, tear proteins start to be accumulated on the lens and may subsequently undergo conformational changes. Protein adsorption or conformational changes on the lens may lead to discomfort, red eye, or even inflammatory reactions. Although measuring the friction coefficient of contact lens has been linked to comfort degree in vivo, there is not much research about the effects of tear protein deposition on the friction coefficient of the contact lens. Therefore, we investigated the friction coefficient of three distinct materials of contact lenses in two different lysosomal concentrations. We also studied lysozyme deposition on the lens without the influence of friction. The results demonstrated that although the amount of lysozyme deposition was high on all the materials we tested, it was not corresponded to higher friction coefficient. In addition, we investigated the effect of the contact lens care solution we developed on friction coefficient and lysozyme deposition of three different materials of contact lenses. The results showed that the care solution could reduce the increased friction coefficient caused by high lysosomal concentration. Therefore, we proposed a potential mechanism of why lysosomal deposition may result in high friction coefficient for certain types of hydrogel contact lenses.

Rapid, accurate, and sensitive insulin detection is crucial for managing and treating diabetes. A simple sandwich-type electrochemical immunosensor is engineered using gold nanoparticle (AuNP)-adhered metal-organic framework-derived copper-zinc hollow porous carbon nanocubes (Au@Cu

(1) Background: Predicting the survival of patients in end-of-life care is crucial, and evaluating their performance status is a key factor in determining their likelihood of survival. However, the current traditional methods for predicting survival are limited due to their subjective nature. Wearable technology that provides continuous patient monitoring is a more favorable approach for predicting survival outcomes among palliative care patients. (2) Aims and objectives: In this study, we aimed to explore the potential of using deep learning (DL) model approaches to predict the survival outcomes of end-stage cancer patients. Furthermore, we also aimed to compare the accuracy of our proposed activity monitoring and survival prediction model with traditional prognostic tools, such as the Karnofsky Performance Scale (KPS) and the Palliative Performance Index (PPI). (3) Method: This study recruited 78 patients from the Taipei Medical University Hospital’s palliative care unit, with 66 (39 male and 27 female) patients eventually being included in our DL model for predicting their survival outcomes. (4) Results: The KPS and PPI demonstrated an overall accuracy of 0.833 and 0.615, respectively. In comparison, the actigraphy data exhibited a higher accuracy at 0.893, while the accuracy of the wearable data combined with clinical information was even better, at 0.924. (5) Conclusion: Our study highlights the significance of incorporating clinical data alongside wearable sensors to predict prognosis. Our findings suggest that 48 h of data is sufficient for accurate predictions. The integration of wearable technology and the prediction model in palliative care has the potential to improve decision making for healthcare providers and can provide better support for patients and their families. The outcomes of this study can possibly contribute to the development of personalized and patient-centered end-of-life care plans in clinical practice.

Surface topography-induced lineage commitment of human bone marrow stem cells (hBMSCs) has been reported. However, this effect on hBMSC differentiation toward retinal pigment epithelium (RPE)-like cells has not been explored. Herein, a family of cell culture substrates called binary colloidal crystals (BCCs) was used to stimulate hBMSCs into RPE-like cells without induction factors. Two BCCs, named SiPS (silica (Si)/polystyrene (PS)) and SiPSC (Si/carboxylated PS), having similar surface topographies but different surface chemistry was used for cell culture. The result showed that cell proliferation was no difference between the two BCCs and tissue culture polystyrene (TCPS) control. However, the cell attachment, spreading area, and aspect ratio between surfaces were significantly changed. For example, cells displayed more elongated on SiPS (aspect ratio ~7.0) than those on SiPSC and TCPS (~2.0). The size of focal adhesions on SiPSC (~1.6 µm

Retinal neovascularization, or pathological angiogenesis in the retina, is a leading cause of blindness in developed countries. Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) activated by TGF-β1 and other proinflammatory cytokines. TAK1 is also a key mediator of proinflammatory signals and plays an important role in maintaining vascular integrity upon proinflammatory cytokine stimulation such as TNFα. However, its role in pathological angiogenesis, particularly in retinal neovascularization, remains unclear. Here, we investigate the regulatory role of TAK1 in human endothelial cells responding to inflammatory stimuli and in a rat model of oxygen-induced retinopathy (OIR) featured retinal neovascularization. Using TAK1 knockout human endothelial cells that subjected to inflammatory stimuli, transcriptome analysis revealed that TAK1 is required for activation of NFκB signaling and mediates its downstream gene expression related to endothelial activation and angiogenesis. Moreover, pharmacological inhibition of TAK1 by 5Z-7-oxozeaenol attenuated angiogenic activities of endothelial cells. Transcriptome analysis also revealed enrichment of TAK1-mediated NFκB signaling pathway in the retina of OIR rats and retinal neovascular membrane from patients with proliferative diabetic retinopathy. Intravitreal injection of 5Z-7-oxozeaenol significantly reduced hypoxia-induced inflammation and microglial activation, thus attenuating aberrant retinal angiogenesis in OIR rats. Our data suggest that inhibition of TAK1 may have therapeutic potential for the treatment of retinal neovascular pathologies.

The innovative plasmon-activated water (PAW) with reduced hydrogen bonds exhibits intrinsically distinct properties at room temperature, which are significantly different from the properties of untreated conventional deionized (DI) water. Examples of this are their ability to scavenge free radicals and higher vapor pressure. However, distinct properties of energetic PAW decay within the day after its creation in a metastable liquid state. In this work, we report a facile method for persisting its distinct activities by letting as-prepared PAW be quickly frozen in liquid nitrogen and letting the frozen PAW (for one month before further measurements) be quickly melted to room temperature in a warm-water bath (called treated PAW). Experimental results indicate that the activity of the higher evaporation rate of treated PAW compared to DI water can be maintained ca. 90% of magnitude, as compared to the as-prepared PAW. Also, its abilities to scavenge free hydroxyl and 2,2-diphenyl-1-picrylhydrazyl radicals can be maintained at ca. 70 and 80% of magnitudes, respectively. Moreover, this strategy of quickly freezing and melting treatments to PAW on persisting in distinct activity of PAW is effective in oxygen evolution reactions. This promises the stored energy and the distinct property of created liquid PAW being available in water-related fields after long-term storage.

Retinal neovascularization, or pathological angiogenesis in the retina, is a leading cause of blindness in developed countries. Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) activated by TGF-β1 and other pro-inflammatory cytokines. TAK1 is also a key mediator of inflammation, innate immune responses, apoptosis and tissue homeostasis and plays an important role in physiological angiogenesis. Its role in pathological angiogenesis, particularly in retinal neovascularization, remains unclear. We investigated the regulatory role of TAK1 in pathological angiogenesis in the retina. Transcriptome analysis of human retina featuring retinal neovascularization revealed enrichment of known TAK1-mediated signaling pathways. Selective inhibition of TAK1 activation by 5Z-7-oxozeaenol attenuated aberrant retinal angiogenesis in rats following oxygen-induced retinopathy. Transcriptome profiling revealed that TAK1 activation in human microvascular endothelial cells under TNFα stimulation led to increase the gene expression related to cytokines and leukocyte-endothelial interaction, mainly through nuclear factor kappa B (NFκB) signaling pathways. These results reveal that inhibition of TAK1 signaling may have therapeutic value for the treatment of pathological angiogenesis in the retina.

Vitreoretinal surgeries for ocular diseases such as complicated retinal detachment, diabetic retinopathy, macular holes and ocular trauma has led to the development of various tamponades over the years in search for an ideal vitreous substitute. Current clinically used tamponade agents such as air, perfluorocarbons, silicone oil and expansile gases serve only as a short-term solution and harbors various disadvantages. However, an ideal long-term substitute is yet to be discovered and recent research emphasizes on the potential of polymeric hydrogels as an ideal vitreous substitute. This review highlights the recent progress in the field of vitreous substitution. Suitability and adverse effects of various tamponade agents in present day clinical use and biomaterials in the experimental phase have been outlined and discussed. In addition, we introduced the anatomy and functions of the native vitreous body and the pathological conditions which require vitreous replacement.

Dry eye syndrome (DES) is a multifactorial disorder of the ocular surface affecting many people all over the world. However, there have been many therapeutic advancements for the treatment of DES, substantial long-term treatment remains a challenge. Natural plant-based polysaccharides have gained much importance in the field of tissue engineering for their excellent biocompatibility and unique physical properties. In this study, polysaccharides from a Chinese ground orchid, Bletilla striata, were successfully extracted and incorporated into the artificial tears for DES treatment due to its anti-inflammatory and mucoadhesive properties. The examination for physical properties such as refractive index, pH, viscosity and osmolality of the Bletilla striata polysaccharide (BSP) artificial tears fabricated in this study showed that it was in close association with that of the natural human tears. The reactive oxygen species (ROS) level and inflammatory gene expression tested in human corneal epithelium cells (HCECs) indicated that the low BSP concentrations (0.01%&ndash, 0.1% v/v) could effectively reduce inflammatory cytokines (TNF, IL8) and ROS levels in HCECs, respectively. Longer retention of the BSP-formulated artificial tears on the ocular surface is due to the mucoadhesive nature of BSP allowing lasting lubrication. Additionally, a rabbit&rsquo, s DES model was created to evaluate the effect of BSP for treating dry eye. Schirmer test results exhibited the effectiveness of 0.1% (v/v) BSP-containing artificial tears in enhancing the tear volume in DES rabbits. This work combines the effectiveness of artificial tears and anti-inflammatory herb extract (BSP) to moisturize ocular surface and to relieve the inflammatory condition in DES rabbit, which further shows great potential of BSP in treating ocular surface diseases like DES in clinics in the future.

Hsin-Yi Huang,1,2,* Ming-Chen Wang,2,* Zhi-Yu Chen,1 Wen-Ying Chiu,1 Ko-Hua Chen,3,4 I-Chan Lin,4,5 Wei-Chung Vivian Yang,6 Chi-Chang Wu,7 Ching-Li Tseng1,8,9 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 2Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan City, Taiwan; 3Department of Ophthalmology, Taipei Veterans General Hospital, Taipei City, Taiwan; 4Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; 5Department of Ophthalmology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 6PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan; 7Department of Electronic Engineering, Feng Chia University, Taichung City, Taiwan; 8International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 9International PhD Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan *These authors contributed equally to this work Introduction: Dry-eye syndrome (DES) is a general eye disease. Eye drops are the common ophthalmological medication. However, the ocular barrier makes it difficult to attain high drug bioavailability. Nanomedicine is a promising alternative treatment for ocular diseases and may increase drug content in the affected eye. Methods: To explore this potential, we constructed nanoparticles (NPs) containing an anti-inflammatory agent for DES treatment. The NPs were made of gelatin–epigallocatechin gallate (EGCG) with surface decoration by hyaluronic acid (HA) and designated “GEH”. The particle size, surface charge, and morphology were evaluated. The in vitro biocompatibility and anti-inflammation effect of nanoparticles were assayed via culturing with human corneal epithelium cells (HCECs) and in vivo therapeutic effect was examined in a DES rabbit’s model. Results: The synthesized GEH NPs had a diameter of approximately 250 nm and were positively charged. A coculture experiment revealed that 20 µg/mL GEH was not cytotoxic to HCECs and that an EGCG concentration of 0.2 µg/mL downregulated the gene expression of IL1B and IL6 in inflamed HCECs. Large amounts of GEH NPs accumulated in the cytoplasm of HCECs and the ocular surfaces of rats and rabbits, indicating the advantage of GEH NPs for ocular delivery of medication. Twice-daily topical treatment with GEH NPs was performed in a rabbit model of DES. The ocular surface of GEH-treated rabbits displayed normal corneal architecture with no notable changes in inflammatory cytokine levels in the cornea lysate. The treatment improved associated clinical signs, such as tear secretion, and fluorescein staining recovered. Conclusion: We successfully produced GEH NPs with high affinity for HCECs and animal eyes. The treatment can be delivered as eye drops, which retain the drug on the ocular surface for a longer time. Ocular inflammation was effectively inhibited in DES rabbits. Therefore, GEH NPs are potentially valuable as a new therapeutic agent delivered in eye drops for treating DES. Keywords: gelatin nanoparticles, epigallocatechin gallate, EGCG, hyaluronic acid, HA, dry-eye syndrome, DES, anti-inflammation

The population of soft contact lens wearers is increasing, thus the issues of feeling comfortable and contact lens-induced clinical symptoms are concerned. Both lysozyme deposition and mechanical friction among contact lens and the eye can induce discomfort and eye conditions. Therefore, we characterized our developed preservative-free contact lens care solution on lysozyme adsorption and lubrication. Two distinct lens materials were washed with the care solution after being soaked in lysozyme, as well as were rubbed against the glass in the presence of lysozyme and the care solution for measuring the friction coefficient. Our results demonstrated that the preservative-free contact lens care solution can be applied as a potential lubricant for a specific type of soft contact lenses.

Conventionally, electrochemical polymerization of polypyrrole (PPy) was generally performed in deionized (DI) water-based electrolyte. In this work, an innovative and facile strategy to substantially enhance the electroactive surface areas of electrochemically polymerized PPy is proposed by using plasmon-activated water (PAW)-based electrolyte. Compared to the DI water-based system, the prepared PPy with higher electron transfer rate and more-reversible redox performance was observed by using PAW-based system. In addition, a greater electroactive surface area of three-dimensional PPy was obtained with PAW-based electrolyte. These distinct properties of PPy electrodes prepared with PAW were responsible for their better performances in supercapacitors (with ca. 25.2% increased capacitance) and sensors (with ca. 50.0% increased sensitivity), compared to those prepared with DI water. These encouraging findings show the potential of PPy prepared with newly developed PAW for application to PPy-related devices to further enhance various performances.

An osteoconductive scaffold can facilitate bone defect repair. In this study, a novel elastic porous composite comprising poly(propylene carbonate) (PPC), poly(D-lactic acid) (PDLA), and β-tricalcium phosphate (β-TCP) was prepared as an osteoconductive scaffold. A salt-leaching method is a non-solvent and easily operated method used to mold up the porous scaffolds. The cylinder scaffold was implanted into a 5 mm in diameter and 10 mm in height rabbit femur condyle defect in 6 rabbits. 4 other rabbits with the same defect that did not have the scaffold implanted served as a control group. Rabbits bone tissue specimens were retrieved at 4 and 12 weeks after surgery. 3 reconstructed and 2 unreconstructed rabbits were examined at each time point. The assessments included a computed tomography (CT) scan and a histological examination. The results demonstrate that a PDT porous scaffold made at a PPC/PDLA/TCP weight ratio of 90/8/2 is (1) biocompatible, yielding a positive cell culture study and minimal inflammatory response in vivo; (2) malleable, such that the scaffold can be molded into the bone defect easily without fracturing; and (3) biodegradable and osteoconductive, promoting the progressive formation of new bone into the bone defect. These results indicated that combination of this scaffold with osteoinductive agents such as bone morphogenetic protein, demineralized bone matrix, or mesenchymal cells may generate new biomaterial for bone defect repair.

Feeling comfortable is an important issue for contact lens wearers as contact lenses are worn for an extensive period of time. It has been shown that the in vitro friction coefficient of contact lenses is correlated to the degree of in vivo comfort, thus many studies focus on establishing friction testing methods for investigating the friction coefficient of contact lenses or contact lens care solution. We have previously demonstrated the lubricating property of poly-gamma-glutamic acid (&gamma, PGA)-containing care solution, and it could reduce the high friction coefficient caused by lysozyme. However, the mechanism of how &gamma, PGA-containing care solution reduces the lysozyme-induced friction coefficient of contact lenses is unclear. We investigated the bio-tribological effect of &gamma, PGA on ionic contact lenses in the presence of lysozyme by testing load and velocity variations. The ability to remove lysozyme deposition by &gamma, PGA and viscosity analysis of &gamma, PGA-containing care solutions were also investigated to understand the potential mechanism. Our results showed that the friction coefficient of &gamma, PGA-containing care solution with lysozyme was the lowest in both load and velocity variations, and &gamma, PGA functions distinctly in the lysozyme-ionic contact lens system. We proposed a model of how &gamma, PGA could reduce the friction coefficient in these two conditions.

Epigallocatechin gallate (EGCG) has many biological functions; however, the use of EGCG in biomedical and food industries was limited due to its poor oral absorption and high susceptibility to degradation. In this study, a mucoadhesive quaternary chitosan was synthesized and combined with fucoidan (FD) (or depolymerized lower molecular weight fucoidan, LMWF) to prepare EGCG-loaded nanoparticles, which extended EGCG release over 300 min and enhanced the transepithelial permeation of EGCG using Caco-2 cells as a model for intestinal absorption. The nanoparticls protected EGCG against degradation in phosphate buffer (pH 6.8) and the remaining EGCG was 1.7-folds higher than the control (EGCG alone). The additive effects of EGCG combined with FD or LMWF in the nanoparticles increased the DPPH radical scavenging activity and the enzyme inhibitory activity against α-amylase (2.82–4.92 fold increase) and α-glucosidase (1.35–1.67 fold increase), while quaternary chitosan helped to enhance the antibacterial effect of EGCG.

The culture environment plays an important role for stem cells&rsquo, cultivation. Static or dynamic culture preserve differential potentials to affect human mesenchymal stem cells&rsquo, (hMSCs) proliferation and differentiation. In this study, hMSCs were seeded on fiber disks and cultured in a bidirectional-flow bioreactor or spinner-flask bioreactor with a supplement of osteogenic medium. The hMSCs&rsquo, proliferation, osteogenic differentiation, and extracellular matrix deposition of mineralization were demonstrated. The results showed that the spinner flask improved cell viability at the first two weeks while the bidirectional-flow reactor increased the cell proliferation of hMSCs through the four-week culture period. Despite the flow reactor having a higher cell number, a lower lactose/glucose ratio was noted, revealing that the bidirectional-flow bioreactor provides better oxygen accessibility to the cultured cells/disk construct. The changes of calcium ions in the medium, the depositions of Ca2+ in the cells/disk constructs, and alkaline phosphate/osteocalcin activities showed the static culture of hMSCs caused cells to mineralize faster than the other two bioreactors but without cell proliferation. Otherwise, cells were distributed uniformly with abundant extracellular matrix productions using the flow reactor. This reveals that the static and dynamic cultivations regulated the osteogenic process differently in hMSCs. The bidirectional-flow bioreactor can be used in the mass production and cultivation of hMSCs for applications in bone regenerative medicine.

In order to perform the multiple functions of disinfection, cleansing, and storage, preservatives are often added to contact lens care solutions. The disadvantage of adding preservatives is that this often causes various eye conditions. However, lens care solutions would not be able to disinfect in the absence of such preservatives. In addition, comfort is an important issue for contact lens wearers due to the long periods of time they are worn. It has been shown that lower friction coefficients are correlated with increased comfort. We have previously developed a multipurpose contact lens care solution in which poly-gamma-glutamic acid (&gamma, PGA) was the main ingredient. In this study, we investigated the antimicrobial activity and lubricating property of our care solution. We showed that there was a synergetic effect of &gamma, PGA and chlorine dioxide on antimicrobial activity. We also demonstrated that &gamma, PGA functioned as a lubricating agent. Our results provided evidence of &gamma, PGA acting as a multi-functional polymer that could be applied in contact lens care solutions.

In recent years, obesity has become a major problem in the western world, affecting almost one-third of the population. Treatment for obesity is very expensive; therefore, the ‘fat-busting’ hormone leptin (LEP) has provoked wide-ranging interest over the last few years, and the immunosensing of LEP has received considerable attention in the field of obesity diagnosis. Bimetal oxides are significantly promising materials for biosensor applications owing to their large surface area, high stability, many active sites, and good biocompatibility. In this study, cerium niobate/cerium oxide (Ce3NbO7/CeO2) hollow nanospheres were synthesized using a template-free hydrothermal technique. The Ce3NbO7/CeO2 exhibits the high catalytic activity, large surface area, porous nature, and more active sites towards the LEP immunosensor. To improve the conductivity of the electrode, the AuNPs were decorated through the electrodeposition method (potential range: -0.4 to -0.9 V with an optimum successive cycle of 20). Au/Ce3NbO7/CeO2 was then thiol factionalized (Au-S bond-forming) with MPA to obtain a strong surface. Consequently, EDC/NHS enabled the −COOH group activation and firmly bonded with the anti-LEP molecules. Under optimal conditions, the developed immunosensor exhibited a good linear range from 0.5 pg/mL to 12,000 ± 500 pg/mL with a low detection limit (LOD) of 0.138 pg/mL, and good precision, selectivity, and stability results achieved for the immunosensing of LEP. Furthermore, the practical feasibility of LEP was demonstrated in plasma samples.

Che-Yi Chang,1,2,* Ming-Chen Wang,2,* Takuya Miyagawa,1 Zhi-Yu Chen,1 Feng-Huei Lin,3,4 Ko-Hua Chen,5,6 Guei-Sheung Liu,7 Ching-Li Tseng1 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 2Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan, 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, 4Institute of Biomedical Engineering, National Taiwan University, 5Department of Ophthalmology, Taipei Veterans General Hospital, 6Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 7Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia *These authors contributed equally to this work Abstract: Neovascularization (NV) of the cornea can disrupt visual function, causing ocular diseases, including blindness. Therefore, treatment of corneal NV has a high public health impact. Epigalloccatechin-3-gallate (EGCG), presenting antiangiogenesis effects, was chosen as an inhibitor to treat human vascular endothelial cells for corneal NV treatment. An arginine–glycine–aspartic acid (RGD) peptide–hyaluronic acid (HA)-conjugated complex coating on the gelatin/EGCG self-assembly nanoparticles (GEH-RGD NPs) was synthesized for targeting the αvβ3 integrin on human umbilical vein endothelial cells (HUVECs) in this study, and a corneal NV mouse model was used to evaluate the therapeutic effect of this nanomedicine used as eyedrops. HA-RGD conjugation via COOH and amine groups was confirmed by 1H-nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The average diameter of GEH-RGD NPs was 168.87±22.5 nm with positive charge (19.7±2 mV), with an EGCG-loading efficiency up to 95%. Images of GEH-RGD NPs acquired from transmission electron microscopy showed a spherical shape and shell structure of about 200 nm. A slow-release pattern was observed in the nanoformulation at about 30% after 30 hours. Surface plasmon resonance confirmed that GEH-RGD NPs specifically bound to the integrin αvβ3. In vitro cell-viability assay showed that GEH-RGD efficiently inhibited HUVEC proliferation at low EGCG concentrations (20 µg/mL) when compared with EGCG or non-RGD-modified NPs. Furthermore, GEH-RGD NPs significantly inhibited HUVEC migration down to 58%, lasting for 24 hours. In the corneal NV mouse model, fewer and thinner vessels were observed in the alkali-burned cornea after treatment with GEH-RGD NP eyedrops. Overall, this study indicates that GEH-RGD NPs were successfully developed and synthesized as an inhibitor of vascular endothelial cells with specific targeting capacity. Moreover, they can be used in eyedrops to inhibit angiogenesis in corneal NV mice. Keywords: RGD peptide, epigallocatechin gallate (EGCG), hyaluronic acid (HA), vascular endothelial cells, antiangiogenesis, corneal neovascularization

The lack of optimal methods employing nanoparticles to administer local anesthesia often results in posing severe risks such as non-biocompatibility, in vivo cytotoxicity, and drug overdose to patients. Here, we employed magnetic field-induced hyperthermia to achieve localized anesthesia. We synthesized iron&ndash, gold alloy nanoparticles (FeAu Nps), conjugated an anesthetic drug, Lidocaine, and coated the product with gelatin to increase the biocompatibility, resulting in a FeAu@Gelatin&ndash, Lidocaine nano-complex formation. The biocompatibility of this drug&ndash, nanoparticle conjugate was evaluated in vitro, and its ability to trigger local anesthesia was also evaluated in vivo. Upon exposure to high-frequency induction waves (HFIW), 7.2 &plusmn, 2.8 nm sized superparamagnetic nanoparticles generated heat, which dissociated the gelatin coating, thereby triggering Lidocaine release. MTT assay revealed that 82% of cells were viable at 5 mg/mL concentration of Lidocaine, indicating that no significant cytotoxicity was induced. In vivo experiments revealed that unless stimulated with HFIW, Lidocaine was not released from the FeAu@Gelatin&ndash, Lidocaine complex. In a proof-of-concept experiment, an intramuscular injection of FeAu@Gelatin&ndash, Lidocaine complex was administered to the rat posterior leg, which upon HFIW stimulation triggered an anesthetic effect to the injected muscle. Based on our findings, the FeAu@Gelatin&ndash, Lidocaine complex can deliver hyperthermia-induced controlled anesthetic drug release and serve as an ideal candidate for site-specific anesthesia administration.

Polymer-based nanoparticles (PNPs) are attractive in part due to their ultra-small size, versatility and target specificity. Therefore, PNPs have been increasingly used in a variety of biomedical applications including diagnoses and therapeutic treatment. In this chapter, we focus on the recent studies (within 5 years) with some new ideas/agent's application in biomedical field and roughly divide applications of PNPs into four categories: (1) Delivery, (2) In vivo imaging, (3) Therapies, and (4) Other applications. First, we introduce how PNPs can enhance the treatment and delivery efficiency of therapeutic agent. Second, how PNPs can be used to help in vivo imaging system for disease tracking and monitor. Then, we reveal some novel PNPs which is able to function as an agent in photodynamic, photothermal, sonodynamic and neuron capture therapy. Furthermore, we also mention some interesting applications of PNPs for biomedical field in individual form or cluster employment, such as immunoswitch particles, surface fabrication. Finally, the challenges and future development of PNPs are also discussed. In delivery section, we focus on how polymer "can be used" as vehicles in delivery application. But, in the section of imaging and therapies, we carried on how polymer as an "adjuvant" for functional enhancement. The biodegradable property of PNPs is the feature that they can be controllable for itself degradation and drug release as a chief actor. Besides, in imaging and therapies application, PNPs can be the support role for helping contrast agent or photo/sonosensitizer to enlarge their imaging or therapeutic effect.

Calcium phosphate ceramics used in dentistry and orthopedics are some of the most valuable biomaterials, owing to their excellent osteoconduction, osteoinduction, and osseointegration. Osteoconduction and osteoinduction are critical targets for bone regeneration, and osseointegration is essential for any dental implantations. In this study, a hydroxyapatite (HAp) hybrid coating layer with the sequential release of bone morphogenetic protein 2 (BMP-2) was deposited onto an etched titanium substrate by electrochemical deposition. The resulting release of BMP-2 from Ti&ndash, HAp was assessed by immersing samples in a simulated buffer fluid solution. Through coculture, human osteosarcoma cell proliferation and alkaline phosphatase activity were assessed. The characteristics and effect on cell proliferation of the hybrid coatings were investigated for their functionality through X-ray diffraction (XRD) and cell proliferation assays. Findings revealed that &minus, 0.8 V vs. Ag/AgCl (3 M KCl) exhibited the optimal HAp properties and a successfully coated HAp layer. XRD confirmed the crystallinity of the deposited HAp on the titanium surface. Ti-0.8 V Ti&ndash, HAp co-coating BMP sample exhibited the highest cell proliferation efficiency and was more favorable for cell growth. A successful biocompatible hybrid coating with optimized redox voltage enhanced the osseointegration process. The findings suggest that this technique could have promising clinical applications to enhance the healing times and success rates of dental implantation.

Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot prevention and reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs could be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to prevent and lyse fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments. STATEMENT OF SIGNIFICANCE: Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs can be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to disintegrate fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments.