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
ACS Applied Materials & Interfaces
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2017
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IF 7.504
Wen-Jian Zhang,Chun-Yan Hong,Cai-Yuan Pan
Intelligent vesicles are fabricated at up to 30% solid content via an approach of polymerization-induced self-assembly and reorganization (PISR). Upon irradiation with UV light (365 nm), light-triggered dimerization of the coumarin moieties anchored in the membrane leads to the membrane cross-linking of the vesicles, which endows the vesicles with superior structural stability. Due to the tertiary amine groups in the membrane, the vesicles go through a swelling/deswelling change upon switching the pH values. In acidic aqueous solution, the pores in the membrane of vesicles are opened, which is beneficial for transmembrane traffic. The pore size in the membrane of vesicles is in accordance with the extent of membrane cross-linking, which can be conveniently regulated by the irradiation time of UV light (365 nm). The size range of the substance for transmembrane traffic is effectively enlarged; even 15 nm gold nanoparticles can be postloaded into the vesicles with lower extents of the membrane cross-linking through the diffusion method. Although the pores in the vesicle membrane are opened in acidic aqueous solution, transmembrane traffic is inhibited for the electropositive substance because of electrostatic repulsion but is allowed for the electronegative substance. These reported vesicles herein may be the smartest artificial vesicles to date due to their multiple selective permeability.
研究领域:
生物材料学
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化学合成
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纳米医学
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DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-19
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IF 14.7
Yang Mei,Chen Tingting,Chen Xin,Pan Hongxian,Zhao Guoli,Chen Zhongxing,Zhao Nan,Ye Qianfang,Chen Ming,Zhang Shenrong,Gao Rongrong,Meek Keith M.,Hayes Sally,Ma Xiaowei,Li Xin,Wu Yue,Zhang Yiming,Kong Na,Tao Wei,Zhou Xingtao,Huang Jinhai
Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C 3 N 4 ) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C 3 N 4 QDs and riboflavin/g-C 3 N 4 QDs composites (RF@g-C 3 N 4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C 3 N 4 QDs or RF@g-C 3 N 4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5’-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C 3 N 4 QDs in A-CXL for corneal ectasias and other corneal diseases.
研究领域:
生物医学工程
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眼科医学
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材料科学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2025
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IF 5.7
Lin Ye,Zhongwu Bei,Tingyu Yang,Yang Xu,Meng Pan,Hanzhi Deng,Xicheng Li,Longqian Liu,Zhiyong Qian
Corneal collagen cross-linking (CXL) is the effective surgical approach to halt the progression of keratoconus. A key challenge lies in maintaining epithelial integrity while achieving sufficient stromal riboflavin (RF) concentration to ensure the CXL efficacy. Additionally, the efficacy of CXL under RF-mediated cross-linking still has room for improvement. In this study, we developed silk fibroin methacryloyl (SFMA)-based dissolvable microneedles (MNs) system (termed RF/SFMA MNs). In vitro and ex vivo experiments showed that RF/SFMA MNs exhibited excellent mechanical strength, dissolution profile, drug release profile and biocompatibility. In vivo, RF/SFMA MNs were characterized by suitable corneal penetration capability though a minimally invasive approach. MNs with different RF concentrations (0%-2%) and tips length (330-800 μm) were tested. RF/SFMA MNs with a 1% RF concentration and a tip length of 550 μm achieved sufficient RF permeation and delivery depth within the corneal stroma. Furthermore, integrating SFMA into the CXL procedure allowed RF to mediate multiple crosslinking events between SFMA and collagen, resulting in an enhanced increase in corneal biomechanical strength compared to conventional Epi-on and Epi-off CXL strategies. Over a two-week observation period, MN-based CXL enhanced corneal biomechanics more effectively than Epi-off and Epi-on CXL, while maintaining collagen rrangement without adverse effects on the epithelium or endothelium. Therefore, RF/SFMA MNs, designed for minimally invasive RF delivery and enhanced CXL efficacy, present a promising and innovative approach to optimize CXL in the treatment of keratoconus.
研究领域:
眼科学
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材料科学
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药剂学
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DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE SCIENCE
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2025
·
IF 9
Dan Qiu,Yanping Zhang,Zishun Xu,Qing Fang,Jiaqin Cao,Xiuxiu Mu,Fan Hu,Hongxing Liu,Chuner Lin,Linghui Wang
Organic solvent nanofiltration (OSN) has emerged as a promising separation technology for product purification and solvent recycling in organic solution. Crosslinked polyimide (PI) membranes were widely used in the OSN system. However, the existence of some drawbacks, such as low utilization of crosslinkers and generation of profuse organic waste, hindered the development. Furthermore, when crosslinkers of large molecular weight were applied, the crosslinking degree of membranes was usually found to be insufficient, restricting their performance in harsh solvent systems. In this work, PEI with specific protonation degree, performing as a crosslinker, was directly introduced into PI solution for the preparation of OSN membranes. The partially activated PEI would graft onto PI chains, which could improve the retention of PEI chains during the membrane forming process, while preventing the gelation of PI solution. The as-prepared PEI/PI membrane showed enhanced hydrophilicity and highly positive charge with the isoelectric point as high as 9.1. The PEI/PI membranes were post-treated by K 2 CO 3 solution, aiming to further improve the crosslinking degree. The PEI/PI membranes exhibited good organic solvent resistance even in N, N-dimethylformamide (DMF), with the tensile strength of 0.28 MPa and permeance of 2.38 L m −2 h −1 bar −1 . Meanwhile, the dye/salt separation performance of the membrane was carried out by using DMF/H 2 O (1:9 w/w) as the solvent, and the rejection for several dyes was above 97 %, with the rejection for salts below 8 %. After 80 h test, the membrane maintained high rejection for Congo Red and Methyl Blue and low rejection for salt, with the permeation retained at 20 L m −2 h −1 bar −1 , indicating excellent anti-fouling performance. The controlled activation method takes the advantage of high utilization and reaction efficiency, as well as simple procedure, rendering it valuable for fabrication of OSN membranes.
研究领域:
材料科学
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膜技术
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分离科学
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高分子化学
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化学工程
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产品关联
DOI
高影响因子
Materials Today Bio
·
2025
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IF 10.2
Yi Liao,Shengmei Zhou,Andrew J. Quantock,Wei Li,Yuan Xu,Xie Fang,Robert D. Young,Wanling He,Qingjian Li,Houjian Zhang,Ruochen Wang,Yi Han,Hongwei Cheng,Wenjun Li,Lu Peng,Rongrong Zong,Yi Hong,Zhirong Lin,Zuguo Liu
Although cell-encapsulating hydrogels are of tremendous interest in regenerative medicine, few of them have been used in clinics and rarely used natural extracellular matrices as polymer precursors. One successful example is to use riboflavin (RF)/ultraviolet A (UVA) to cross-link corneal collagen, which has been used in clinics to halt disease progression in patients with corneal ectatic diseases. However, high-energy UVA and its action on RF cause tissue damage, particularly irreversible endothelium loss, and thus standard RF/UVA protocol may have limitations in treating patients at the advanced stage with thin cornea. Photo-initiators lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) has high efficiency under visible 405 nm light, and is widely applied in 3D bioprinting to cross-link synthesized monomers. Here, we introduced a new strategy to cross-link cornea using LAP and visible light (VL). The LAP/VL protocol could effectively increase corneal stiffness with equivalent efficiency to the RF/UVA protocol in both porcine and rabbit cornea. As LAP and VL were used, the loss of corneal endothelial and stromal cells was minimized, and epithelial wound healing and stromal cell repopulation were accelerated. In summary, we propose that the LAP/VL protocol is an effective and safe alternate for cornea CXL with advantages for relatively thin cornea. Our study also expands the application scope of LAP, indicating it is a suitable photocatalyst for in situ natural extracellular matrices CXL.
研究领域:
眼科学
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再生医学
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生物材料
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光生物学
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组织工程
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产品关联
DOI
PubMed
高影响因子
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