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

被引:96
作者
He, Binbin [1 ]
Wang, Jie [2 ]
Xie, Mengtian [1 ]
Xu, Miaoyi [1 ]
Zhang, Yahan [1 ]
Hao, Huijie [3 ,4 ]
Xing, Xiaoli [3 ,4 ]
Lu, William [5 ]
Han, Quanhong [2 ]
Liu, Wenguang [1 ]
机构
[1] Tianjin Univ, Sch Mat Sci & Engn, Tianjin Key Lab Composite & Funct Mat, Tianjin 300350, Peoples R China
[2] Tianjin Med Univ, Tianjin Eye Hosp, Clin Coll Ophthalmol, Tianjin Eye Inst,Tianjin Key Lab Ophthalmol & Vis, Gansu Rd 4, Tianjin 300020, Peoples R China
[3] Tianjin Med Univ, Tianjin Int Joint Res & Dev Ctr Ophthalmol & Vis, Eye Inst, Eye Hosp, Tianjin 300384, Peoples R China
[4] Tianjin Med Univ, Sch Optometry, Eye Hosp, Tianjin 300384, Peoples R China
[5] Univ Hong Kong, Dept Orthopaed & Traumotol, 21 Sassoon Rd, Hong Kong, Peoples R China
关键词
3D printing; Hydrogel; Bi-layer scaffold; Corneal regeneration; DIFFERENTIATION;
D O I
10.1016/j.bioactmat.2022.01.034
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:234 / 247
页数:14
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