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A long-term retaining molecular coating for corneal regeneration

Bioactive Materials 2021年第12期6卷 4447-4454页

作者： Yi Zhang Chenglin Li Qiuwen Zhu Renjie Liang Chang Xie Shufang Zhang Yi Hong Hongwei Ouyang Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cells and Regenerative Medicine Department of Orthopedic Surgery of the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Zhejiang University-University of Edinburgh Institute Zhejiang University School of MedicineKey Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang ProvinceZhejiang University School of MedicineHangzhouChina Department of Sports Medicine Zhejiang University School of MedicineHangzhouChina China Orthopedic Regenerative Medicine Group(CORMed) HangzhouChina

corneal injuries will cause corneal surface diseases that may lead to blindness in millions of people *** is a tremendous need for biomaterials that can promote corneal regeneration with practical *** we demonstrate a strategy of a protein coating for corneal injury *** 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 *** molecular coating could avoid rapid clearance and provide a favorable environment for cell migration,thereby effectively accelerating corneal repair and *** histological structure of the regenerated cornea is more similar to the native *** molecular coating can be used conveniently as an eye drop solution,which makes it a promising strategy for corneal regeneration.

关键词： corneal regeneration GelNB molecular coating Long-term adhesion Eye drops

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3D printed biomimetic epithelium/stroma bilayer hydrogel implant for corneal regeneration

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Bioactive Materials 2022年第11期7卷 234-247页

作者： Binbin He Jie Wang Mengtian Xie Miaoyi Xu Yahan Zhang Huijie Hao Xiaoli Xing William Lu Quanhong Han Wenguang Liu School of Material Science and Engineering Tianjin Key Laboratory of Composite and Functional MaterialsTianjin UniversityTianjin300350China Clinical College of Ophthalmology Tianjin Medical UniversityTianjin Key Lab of Ophthalmology and Visual ScienceTianjin Eye InstituteTianjin Eye HospitalGansu Road 4Heping DistrictTianjin300020China Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science Eye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin300384China Department of Orthopaedic and Traumotology The University of Hong Kong21 Sassoon RdHong KongPR China

corneal regeneration has always been a challenge due to its sophisticated structure and undesirable keratocyte-fibroblast transformation. Herein, we propose 3D printing of a biomimetic epithelium/stroma bilayer implant for corneal regeneration. Gelatin methacrylate (GelMA) and long-chain poly(ethylene glycol) diacrylate (PEGDA) are blended to form a two-component ink, which can be printed to different mechanically robust programmed PEGDA-GelMA objects by Digital Light Processing (DLP) printing technology, due to the toughening effect of crystalline crosslinks from long-chain PEGDA on GelMA hydrogel after photo-initiated copolymerization. The printed PEGDA-GelMA hydrogels support cell adhesion, proliferation, migration, meanwhile demonstrating a high light transmittance, and an appropriate swelling degree, nutrient permeation and degradation rate. A bi-layer dome-shaped corneal scaffold consisting of rabbit corneal epithelial cells (rCECs)-laden epithelia layer and rabbit adipose-derived mesenchymal stem cells (rASCs)-laden orthogonally aligned fibrous stroma layer can be printed out with a high fidelity and robustly surgical handling ability. This bi-layer cells-laden corneal scaffold is applied in a rabbit keratoplasty model. The post-operative outcome reveals efficient sealing of corneal defects, re-epithelialization and stromal regeneration. The concerted effects of microstructure of 3D printed corneal scaffold and precisely located cells in epithelia and stroma layer provide an optimal topographical and biological microenvironment for corneal regeneration.

关键词： 3D printing Hydrogel Bi-layer scaffold corneal regeneration

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Photoactivated growth factor release from bio-orthogonally crosslinkedhydrogels for the regeneration of corneal defects

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Bioactive Materials 2024年第10期40卷 417-429页

作者： Nae-Won Kang Youngyoon Amy Seo Kevin JJackson Kyeongwoo Jang Euisun Song Uiyoung Han Fang Chen Sarah CHeilshorn David Myung Department of Ophthalmology Byers Eye Institute at Stanford UniversitySchool of MedicinePalo AltoCA 94304United States Department of Materials Science and Engineering Stanford UniversityStanfordCA 94305United States Department of Chemical Engineering Stanford UniversityPalo AltoCA 94305United States VA Palo Alto HealthCare System Palo AltoCA 94304United States

In situ-forming hydrogels are an attractive option for corneal regeneration, and the delivery of growth factorsfrom such constructs have the potential to improve re-epithelialization and stromal remodeling. However,challenges persist in controlling the release of therapeutic molecules from hydrogels. Here, an in situ-forming bioorthogonallycrosslinked hydrogel containing growth factors tethered via photocleavable linkages (PC-HAColhydrogel) was developed to accelerate corneal regeneration. Epidermal growth factor (EGF) was conjugated tothe hydrogel backbone through photo-cleavable (PC) spacer arms and was released when exposed to mild intensityultraviolet (UV) light (2–5 mW/cm^(2), 365 nm). The PC-HACol hydrogel rapidly gelled within a few minuteswhen applied to corneal defects, with excellent transparency and biocompatibility. After subsequentexposure to UV irradiation, the hydrogel promoted the proliferation and migration of corneal epithelial cells invitro. The rate of re-epithelialization was positively correlated to the frequency of irradiation, verified through exvivo rabbit cornea organ culture studies. In an in vivo rat corneal wound healing study, the PC-HACol hydrogelexposed to UV light significantly promoted re-epithelialization, the remodeling of stromal layers, and exhibitedsignificant anti-scarring effects, with minimal α-SMA and robust ALDH3A1 expression. Normal differentiation ofthe regenerated epithelia after healing was evaluated by expression of the corneal epithelial biomarker, *** remodeled cornea exhibited full recovery of corneal thickness and layer number without hyperplasia of theepithelium.

关键词： In situ-forming hydrogel Bio-orthogonally crosslinked hydrogel corneal regeneration Photo-responsive release Growth factor delivery

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