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Herein, concentrated aqueous solutions of gelatin and carbohydrazide-modified alginate (Gel\/Alg-CDH) are blended to form a natural polymer hydrogel ink, where the hydrazides in Alg-CDH are found to form strong hydrogen bonds with the gelatin. The hydrogen-bonding-strengthened Gel\/Alg-CDH hydrogel demonstrates an appropriate thickened viscosity and shear thinning for extrusion printing. The strong hydrogen bonds contribute to remarkably increased mechanical properties of Gel\/Alg-CDH hydrogel with a maximum elongation of over 400%. In addition, sequentially Ca2+-physical crosslinking and then moderately chemical crosslinking significantly enhance the mechanical properties of Gel\/Alg-CDH hydrogels that ultimately exhibit an intriguing J-shaped stress\u2013strain curve (tensile strength of 1.068\u2009MPa and the toughness of 677.6\u2009kJ\/m2). The dually crosslinked Gel-Alg-CDH-Ca2+-EDC hydrogels demonstrate a high transparency, physiological swelling stability and rapid enzymatic degradability, as well as suturability. The growth factor and drug-loaded biomimetic bilayer hydrogel scaffold are customized via a multi-nozzle printing system. This bioactive bilayer hydrogel scaffold considerably promotes regeneration of corneal epithelium and stroma and inhibits cornea scarring in rabbit cornea keratoplasty.<\/jats:p>","DOI":"10.1093\/rb\/rbae012","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T10:34:46Z","timestamp":1707302086000},"source":"Crossref","is-referenced-by-count":27,"title":["3D printing sequentially strengthening high-strength natural polymer hydrogel bilayer scaffold for cornea regeneration"],"prefix":"10.1093","volume":"11","author":[{"given":"Xiongfeng","family":"Nie","sequence":"first","affiliation":[{"name":"School of Material Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University , Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Tang","sequence":"additional","affiliation":[{"name":"Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute , Tianjin 300020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengling","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Material Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University , Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Material Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University , Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Material Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University , Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Material Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University , Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yage","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Material Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University , Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute , Tianjin 300020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanhong","family":"Han","sequence":"additional","affiliation":[{"name":"Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute , Tianjin 300020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Hui","sequence":"additional","affiliation":[{"name":"Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute , Tianjin 300020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Material Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University , Tianjin 300350, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"2024030710585985800_rbae012-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2015.07.001","article-title":"Corneal structure and transparency","volume":"49","author":"Meek","year":"2015","journal-title":"Prog Retin Eye Res"},{"key":"2024030710585985800_rbae012-B2","doi-asserted-by":"crossref","first-page":"101011","DOI":"10.1016\/j.preteyeres.2021.101011","article-title":"Regenerative therapy for the cornea","volume":"87","author":"Kumar","year":"2022","journal-title":"Prog Retin Eye Res"},{"key":"2024030710585985800_rbae012-B3","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0161-6420(94)31376-5","article-title":"Corneal graft survival and visual outcome. 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