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Implementing defined and selective responsiveness to external stimuli is a persisting challenge that critically restricts their functionality. Addressing this challenge, this study introduces a versatile, modular hydrogel system composed of four\u2010arm poly(ethylene glycol)(starPEG)\u2010peptide and glycosaminoglycan(GAG)\u2010maleimide conjugates. The gel system features a small peptide sequence that is selectively cleaved by the coagulation factor FXa. In a cell culture environment, where active FXa is absent, the hydrogel remains stable, providing a conducive matrix for the growth of complex tissue structures or organoids. Upon the introduction of FXa, the hydrogel is designed to disintegrate rapidly, enabling the gentle release of the cultivated tissues without impairing their functionality. The efficacy of this approach is demonstrated through the ex vivo development, detachment, and transplantation of human corneal endothelial lamellae, achieving sizes relevant for clinical application in Descemet Membrane Endothelial Keratoplasty (DMEK). Furthermore, the practicality of the hydrogel system is validated in vitro using a de\u2010endothelialized porcine cornea as a surrogate recipient. Since the FXa\u2010cleavable peptide can be integrated into a variety of multifunctional hydrogels, it can pave the way for next\u2010generation scaffold\u2010free tissue engineering and organoid regenerative therapies.<\/jats:p>","DOI":"10.1002\/adhm.202402593","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T05:13:51Z","timestamp":1737522831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["FXa\u2010Responsive Hydrogels to Craft Corneal Endothelial Lamellae"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-3890","authenticated-orcid":false,"given":"Mikhail V.","family":"Tsurkan","sequence":"first","affiliation":[{"name":"Max Bergmann Center of Biomaterials Dresden Leibniz\u2010Institut f\u00fcr Polymerforschung Dresden e. V.  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