ADVANCED MATERIALS
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2022
·Vol. 34
·期 21
·2109865
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IF 32.086
Mei Yang,Wenjin Xu,Zhongxing Chen,Ming Chen,Xiaoyu Zhang,Huanhuan He,Yushan Wu,Xueyang Chen,Tianjiao Zhang,Mengdi Yan,Jieyi Bai,Colm McAlinden,Keith M. Meek,Jinjin Yu,Shengnan Ding,Rongrong Gao,Jinhai Huang,Xingtao Zhou
Riboflavin-5-phosphate (RF) is the most commonly used photosensitizer in corneal cross-linking (CXL), but its hydrophilicity and negative charge limit its penetration through the corneal epithelium into the stroma. To enhance the corneal permeability of RF and promote its efficacy in the treatment of keratoconus, novel hibiscus-like RF@ZIF-8 microsphere composites [6RF@ZIF-8 NF (nanoflake)] are prepared using ZIF-8 nanomaterials as carriers, which are characterized by their hydrophobicity, positive potential, biocompatibility, high loading capacities, and large surface areas. Both hematoxylin and eosin endothelial staining and TUNEL assays demonstrate excellent biocompatibility of 6RF@ZIF-8 NF. In in vivo studies, the 6RF@ZIF-8 NF displayed excellent corneal permeation, and outstanding transepithelial CXL (TE-CXL) efficacy, slightly better than the conventional CXL protocol. Furthermore, the special hibiscus-like structures of 6RF@ZIF-8 NF meant that it has better TE-CXL efficacy than that of 6RF@ZIF-8 NP (nanoparticles) due to the larger contact area with the epithelium and the shorter RF release passage. These results suggest that the 6RF@ZIF-8 NF are promising for transepithelial corneal cross-linking, avoiding the need for epithelial debridement.
研究领域:
眼科学
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Mei Yang,Hongxian Pan,Tingting Chen,Xin Chen,Rui Ning,Qianfang Ye,Aodong Chen,Jiawei Li,Siheng Li,Nan Zhao,Yue Wu,Xueyu Fu,Keith M. Meek,Lingxin Chen,Xiaoying Wang,Zhongxing Chen,Xingtao Zhou,Jinhai Huang
In this study, a novel customized corneal cross-linking (CXL) treatment is explored that utilizes microneedles (MNs) for targeted riboflavin (RF) administration prior to the CXL procedure. Unlike the conventional “one-size-fits-all” approach, this protocol offers an option for more precise and efficacious treatment. To simulate a customized corneal crosslinking technique, four distinct microneedle (MN) molds designs, including circular, semi-circular, annular and butterfly shaped, are crafted for loading an optimized RF-hyaluronic acid solution and for the subsequent fabrication of MN arrays with varying morphologies. These MNs can gently puncture the corneal epithelium while preserving the integrity of the underlying stromal layer. Following the application of these microneedles, RF solution is replenished to enhance the RF content within the stroma through the punctures created by the MNs, resulting in exceptional customized corneal cross-linking effects that are comparable to the conventional epi-off CXL protocol. Additionally, it flattened the corneal curvature within the treated zone and facilitated rapid postoperative recovery of corneal tissue. These findings suggest that the integration of customized microneedle RF delivery with corneal crosslinking technology represents a potential novel treatment modality, holding promise for the tailored treatment of corneal pathologies, and offering a more precise and efficient alternative to traditional methods.
研究领域:
眼科
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生物医学工程
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药剂学
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DOI
PubMed
高影响因子
Diagnostics
·
2021
·Vol. 11
·期 8
·1466
·
IF 3.706
Piotr Kanclerz,Ramin Khoramnia,Xiaogang Wang
Introduction: Accurate assessment of the corneal shape is important in cataract and refractive surgery, both in screening of candidates as well as for analyzing postoperative outcomes. Although corneal topography and tomography are widely used, it is common that these technologies are confused. The aim of this study was to present the current developments of these technologies and particularly distinguish between corneal topography and tomography. Methods: The PubMed, Web of Science and Embase databases were the main resources used to investigate the medical literature. The following
研究领域:
眼科学
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屈光外科学
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影像学
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生物医学工程
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临床诊断学
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DOI
高影响因子
Journal of Functional Biomaterials
·
2023
·Vol. 14
·期 7
·360
·
IF 4.8
Lulu Wang,Yuehai Peng,Wenfang Liu,Li Ren
Corneal disease has become the second leading cause of blindness in the world. Corneal transplantation is currently considered to be one of the common treatments for vision loss. This paper presents a novel approach utilizing dual-crosslinked membranes composed of polyrotaxane multiple aldehydes (PRAs), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and N-hydroxysuccinimide (NHS) in the development process. Collagen was crosslinked, respectively, by EDC/NHS and PRAs to form stable amide bonds and imine groups. Through the formation of a double interpenetrating network, dual-crosslinked (Col-EDC-PRA) membranes exhibited enhanced resistance to collagenase degradation and superior mechanical properties compared to membranes crosslinked with a single crosslinker. Furthermore, Col-EDC-PRA membranes display favorable light transmittance and water content characteristics. Cell experiments showed that Col-EDC-PRA membranes were noncytotoxic and were not significantly different from other membranes. In a rabbit keratoplasty model, corneal stromal repair occurred at 5 months, evidenced by the presence of stromal cells and neo-stroma, as depicted in hematoxylin–eosin-stained histologic sections and optical coherence tomography images of the anterior segment. Moreover, there was no inflammation and corneal neovascularization, as well as no corneal rejection reaction in the surgical area. Overall, the results demonstrated that the dual-crosslinked membranes served effectively for corneal tissue regeneration after corneal defect.Keywords:collagen membrane;corneal repair;corneal regeneration
研究领域:
生物医学工程
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眼科研究
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2019
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IF 0
Xiaoyue Lei,Yong-Guang Jia,Wenjing Song,Dawei Qi,Jiahong Jin,Jia Liu,Li Ren
Corneal transplantation is the widely accepted treatment to restore sight for corneal blindness. To date, because of the global donor cornea shortage, there is a need for alternatives to human donor corneas. Biocompatible collagen is an excellent candidate material for corneal repair in the view of biomimetics. Herein a class of polyrotaxane multiple aldehyde (PRA) cross-linkers based on the host–guest supramolecules of α-cyclodextrins and poly(ethylene glycol) is prepared to cross-link with collagen to fabricate materials for corneal repair. Aldehyde groups from rotaxanes and α-cyclodextrin units can synergistically improve the mechanical and optical properties of PRA cross-linked collagen membranes (Col-PRAs). Compared with counterparts cross-linked by traditional a cross-linker of 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide and N-hydroxy-succinimide, Col-PRAs have better mechanical properties, especially suture resistance as well as optical properties. In vivo lamellar keratoplasty results indicate that Col-PRAs not only can bear tight suturing on a rabbit cornea but also are prone to the remodeling of the epithelium and stroma of the cornea due to the outstanding cell adhesion and proliferation. These novel Col-PRAs exhibit great potential for use in the corneal regeneration.
研究领域:
材料科学
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生物医学工程
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眼科学
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产品关联
DOI
PubMed
STAR Protocols
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2023
·
IF 0
Zitong Yu,Rui Hao,Xi Chen,Lu Ma,Yi Zhang,Hui Yang
Summary Organs-on-chips are microfluidic devices for cell culturing to simulate tissue- or organ-level physiology, providing new solutions other than traditional animal tests. Here, we describe a microfluidic platform consisting of human corneal cells and compartmentalizing channels to achieve fully integrated human cornea’s barrier effects on the chip. We detail steps to verify the barrier effects and physiological phenotypes of microengineered human cornea. Then, we use the platform to evaluate the corneal epithelial wound repair process. For complete details on the use and execution of this protocol, please refer to Yu et al. (2022). 1
研究领域:
生物医学工程
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组织工程
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细胞生物学
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DOI
PubMed
ADVANCED MATERIALS
·
2025
·
IF 26.8
Siyuan Qian,Xuan Wang,Yishun Guo,Wenfang He,Jianhua Yang,Hao Chen,Renlong Li,Lili Su,Xinyi Wang,Yi Shao,Bailiang Wang
In the treatment of infectious keratitis, therapeutic strategies often prioritize enhancing bactericidal efficacy. However, endotoxins released from Gram-negative bacteria cause inflammatory reaction, leading to corneal structural damage and scar formation. Given that polymyxin B (PMB) can bind and neutralize lipopolysaccharide (LPS), this study employs large-pore mesoporous silica nanoparticles (lMSNs) grafted with PMB as carriers for cationic antibacterial carbon quantum dots (CQDs) to prepare CQD@lMSN-PMB, which enables synchronous sterilization and endotoxin neutralization. In the acidic infectious microenvironment, the accelerated release of CQDs eliminates 99.88% bacteria within 2 h, effectively substituting immune mediated sterilization. Notably, CQD@lMSN-PMB exhibits exceptional LPS neutralization performance (2.22 µg LPS/mg CQD@lMSN-PMB) due to its high specific surface area. In an infectious keratitis model, inflammation subsides significantly within the first day of CQD@lMSN-PMB intervention and is completely resolved by day 3. By day 2, interleukin-1β, interleukin-6 and tumor necrosis factor-α in CQD@lMSN-PMB group decrease by 86.99%, 91.15%, and 77.56%, respectively, compared to the CQDs-only sterilization group. Ultimately, corneal integrity and transparency are preserved, with suppressed expressions of fibrosis-related factors including matrix metalloproteinase 9, transforming growth factor-β and α-smooth muscle actin. Therefore, this synchronous sterilization and endotoxin neutralization strategy outperforms monotherapy strategies focused solely on sterilization or endotoxin neutralization.
研究领域:
眼科学
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纳米医学
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感染性疾病
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Xue Jiang,Shuhua Liu,Jiayi Chen,Jiapeng Lei,Wenjing Meng,Xueyang Wang,Zhigang Chu,Wei Li
Ocular injury and infection are significant causes of vision impairment and blindness globally. Effective treatment is, however, challenging due to the physical barrier of the cornea, which restricts drug penetration in the eye, as well as the presence of eye injury that necessitates continuous delivery of growth factors on the ocular surface for cornea healing. Here, we introduce a transformative wearable corneal microneedle (MN) patch designed for efficient therapy of ocular injury and infection. The MN patch comprises water-soluble tips that encapsulate antibacterial nanoparticles (NPs), along with a transformative backing layer that contains epidermal growth factor (EGF). Upon insertion into the eye, the MN tips dissolve swiftly within the cornea stroma, resulting in the release of the antimicrobial NPs to efficiently eradicate bacteria. Meanwhile, the residual backing layer undergoes rapid in situ transformation upon contact with mildly acidic fluid from infected corneal edema, converting into a contact lens that conforms to the eye's surface, which facilitates sustained release of EGF on the ocular surface over 8 h to promote corneal healing. Benefiting from these features, the designed transformative corneal MN patch demonstrates superior efficacy in treating ocular injuries and infections in vivo, offering a promising therapeutic strategy to manage eye diseases.
研究领域:
医学
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药学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
·
2022
·Vol. 261
·期 3
·723-734
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IF 3.535
Zhou Jin,Ding Yuanyuan,Zhang Yongqiang,Zheng Dehui,Yan Lifeng,Guo Mengxiang,Mao Yani,Yang Lihong
Purpose This study was aimed at exploring the function of Exosomes isolated from bone marrow-derived mesenchymal stem cells (BMSC-Exos) in corneal wound healing and at revealing the underlying mechanisms involving the p44/42 mitogen-activated protein kinase (MAPK) pathway. Methods The isolated BMSC-Exos were identified by transmission electron microscopy, Western blot, and nanoparticle tracking analysis. After coculture with BMSC-Exos, the proliferation and migration of human corneal epithelial cells (HCEs) were evaluated. The protein expression of p-MEK/MEK and p44/42 MAPK was detected by Western blot. A mouse model of alkali-burned cornea was established via NaOH exposure. After injection with BMSC-Exos, the pathological changes and expression of α-SMA (a fibrosis marker) and CD31 (a vascularization marker) in corneal tissues were detected. Results BMSC-Exos enhanced the proliferation and migration of HCEs in a dose-dependent manner. The p44/42 MAPK pathway was activated by the treatment of BMSC-Exos, and its blocking using U0126 partially abrogated the effects of BMSC-Exos on promoting the proliferation and migration of HCEs. In vivo , the injection of BMSC-Exos facilitated the remission of the pathological changes (inflammation) and weakened the upregulation of α-SMA (fibrosis) and CD31 (vascularization) in corneal tissues of mice with alkali-burn injury. Conclusion BMSC-Exos promoted the proliferation and migration of HCEs via activating the p44/42 MAPK pathway in vitro and also inhibited alkali burn-induced inflammation, fibrosis, and vascularization in corneal tissues in vivo . BMSC-Exos may be promising resources for promoting corneal wound healing.
研究领域:
眼科学
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干细胞生物学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Yi Zhang,Chenglin Li,Qiuwen Zhu,Renjie Liang,Chang Xie,Shufang Zhang,Yi Hong,Hongwei Ouyang
Corneal injuries will cause corneal surface diseases that may lead to blindness in millions of people worldwide. There is a tremendous need for biomaterials that can promote corneal regeneration with practical feasibility. Here we demonstrate a strategy of a protein coating for corneal injury regeneration. We synthesize an o-nitrosobenzaldehyde group (NB)-modified gelatin (GelNB), which could adhere directly to the corneal surface with covalent bonding to form a thin molecular coating. The molecular coating could avoid rapid clearance and provide a favorable environment for cell migration, thereby effectively accelerating corneal repair and regeneration. The histological structure of the regenerated cornea is more similar to the native cornea. This molecular coating can be used conveniently as an eye drop solution, which makes it a promising strategy for corneal regeneration.
研究领域:
生物材料
·
组织工程
·
眼科
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DOI
高影响因子
Drug Delivery and Translational Research
·
2023
·
IF 5.4
Yu Linrong,Zhang Qiliang,Zhou Liping,Wei Yanjun,Li Mengshuang,Wu Xianggen,Xin Meng
Alpha-glucosyl hesperidin (GH) is an aqueous soluble, amphipathic hesperidin derivative with several pharmacological effects, and it is postulated in this manuscript that GH could potentially be utilized as an active pharmaceutical excipient in eyedrops. The ocular safety of GH was evaluated according to in vitro cytotoxicity and in vivo ocular tolerance. The in vivo corneal permeation of coumarin-6 (Cou-6) with or without GH was characterized, and the in vivo inducing corneal wound healing using bisdemethoxycurcumin (BDMC) with or without GH was also evaluated to determine whether GH is an active pharmaceutical excipient in eyedrops. The results demonstrated that as high as 30 mg/ml of GH exhibits high-level in vitro and in vivo safety profiles according to four in vitro and in vivo evaluations. GH improved the corneal permeation of Cou-6 in mice, as well as demonstrated in vitro antioxidant activity. Concerning in vivo activity, a BDMC–GH suspension was shown to be synergistic in promoting corneal wound healing in mice, as well as restoring corneal sensitivity, promoting corneal epithelial wound healing, and restoring the corneal tissue structure without inflammatory cell infiltration. Overall, GH could be a novel and promising active excipient in eyedrops. Graphical Abstract
研究领域:
药学
·
眼科
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产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2024
·
IF 5.7
Wang Yanan,Shi Shaohua,Zhang Ling,Wang Songtao,Qin Hongqing,Wei Yanjun,Wu Xianggen,Zhang Mengmeng
Imatinib (IMB) is a type of tyrosine kinase inhibitor with great application potential for inhibiting corneal neovascularization (CNV), but its poor water solubility limits its application in eye disease treatment. In this study, novel IMB@glycymicelles entrapped in hydrogel (called IMB@glycymicelle-hydrogel) were prepared, characterized, and evaluated for their therapeutic effects on corneal alkali burn in mice. Imatinib could be successfully loaded in glycymicelles using glycyrrhizin as a nanocarrier with an optimized weight ratio of IMB:nanocarrier. The apparent solubility of IMB was significantly improved from 61.69 ± 5.55 μg/mL to bare IMB to 359,967.62 ± 20,059.42 μg/mL to IMB@glycymicelles. Then, the IMB@glycymicelles were entrapped in hydrogel fabricated with hydroxypropyl methylcellulose and sodium hyaluronate (HA) to prolong retention time on the ocular surface. Rabbit eye tolerance tests showed that IMB@glycymicelle-hydrogel possessed good ocular safety profiles. In a mouse model of corneal alkali burns, the topical administration of IMB@glycymicelle-hydrogel showed strong efficacy by prompting corneal wound healing, recovering corneal sensitivity, relieving corneal opacities, and inhibiting CNV, and these efficacy evaluation parameters were better than those of the positive drug HA. Overall, these results demonstrated that IMB@glycymicelle-hydrogel may be a promising candidate for the effective treatment of alkali ocular damage. Graphical abstract
研究领域:
药学
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眼科
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药物递送系统
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）