{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:26:56Z","timestamp":1788514016378,"version":"build-2803163510"},"reference-count":253,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8246080333"],"award-info":[{"award-number":["8246080333"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["8246080333"],"award-info":[{"award-number":["8246080333"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010857","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20242BAB20434"],"award-info":[{"award-number":["20242BAB20434"]}],"id":[{"id":"10.13039\/501100010857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Programmable peptide hydrogels represent advanced supramolecular biomaterials featured with customizable molecular sequences and tunable self-assembly behaviors, which can biomimetically reconstruct the structural and microenvironmental complexity of native extracellular matrix. This review systematically elaborates the molecular engineering advances of programmable peptide hydrogels following a hierarchical logic from fundamental mechanisms to translational applications. We first interpret the intrinsic self-assembly mechanisms driven by non-covalent interactions and the regulatory effects of typical external microenvironmental stimuli. On this basis, we summarize core rational design principles, covering stimuli-responsive structural optimization, biofunctional modification, and the tunable regulation of physical properties, degradability and immunogenicity. Furthermore, we correlate multi-scale structural features (nanostructures, porous architecture and mechanical properties) with their versatile biomedical functions, and comprehensively discuss their cutting-edge applications in tissue regeneration, targeted drug and gene delivery, cell-mediated therapy, immunomodulation, and anti-infective treatment. Finally, we identify critical translational barriers including batch-to-batch inconsistency, immunogenic risks, and in vivo performance instability, and highlight future directions involving multi-stimuli-responsive systems, artificial intelligence-assisted design, computational modeling, and hybrid material construction. This work systematically clarifies the structure\u2013property\u2013function relationship of peptide hydrogels, and underscores their great potential as next-generation platforms for precision regenerative medicine and targeted disease intervention.<\/jats:p>","DOI":"10.3390\/gels12060527","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:53:10Z","timestamp":1781247190000},"page":"527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fundamentals and Advances in Programmable Peptide Hydrogels for Multifunctional Biomedical Applications: A Review"],"prefix":"10.3390","volume":"12","author":[{"given":"Yihao","family":"Zhao","sequence":"first","affiliation":[{"name":"Queen Mary School, Jiangxi Medical College, Nanchang University, 999 Xuefu Road, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Queen Mary School, Jiangxi Medical College, Nanchang University, 999 Xuefu Road, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Bioengineering Drugs, School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cancan","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Bioengineering Drugs, School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Shen","sequence":"additional","affiliation":[{"name":"Queen Mary School, Jiangxi Medical College, Nanchang University, 999 Xuefu Road, Nanchang 330031, China"},{"name":"Jiangxi Province Key Laboratory of Bioengineering Drugs, School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang 330031, China"},{"name":"National Engineering Research Center for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70187","DOI":"10.1111\/1541-4337.70187","article-title":"Emerging Trends and Future Prospects of Peptide-Based Hydrogels: Revolutionizing Food Technology Applications","volume":"24","author":"Li","year":"2025","journal-title":"Compr. 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