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However, rapid degradation and insufficient mechanical stability limit their effectiveness. This study investigates natural cross\u2010linking strategies utilizing Transglutaminase (TG) and Methylglyoxal (MGO) to enhance scaffold durability while maintaining biocompatibility. Monolayer and bilayer collagen scaffolds were fabricated and cross\u2010linked using enzymatic (TG) and non\u2010enzymatic (MGO) treatments. Cross\u2010linking efficiency was assessed via TNBS\/Hydroxyproline assays, while AFM and mechanical testing evaluated structural and mechanical properties. Cell viability (LIVE\/DEAD), metabolic activity (MTS assay), and cell migration (in\u2010growth and out\u2010growth assays) were analyzed to assess biocompatibility and scaffold functionality. Wound healing was also assessed histologically. TG and MGO crosslinking significantly enhanced collagen fibril organization, scaffold stiffness, and enzymatic resistance. TG\u2010 and MGO\u2010treated scaffolds exhibited a homogeneous fibrillar structure with improved mechanical integrity. Both cross\u2010linking strategies supported high fibroblast viability and sustained metabolic activity over time. Migration assays confirmed that TG and MGO scaffolds facilitated fibroblast infiltration and wound closure. In\u00a0vivo, the bilayer scaffolds with TG\/MGO cross\u2010linking showed full epithelialization, with the Tg\/25 MGO group exhibiting reduced inflammation, organized collagen, and hair follicle formation, suggesting improved regeneration. These findings highlight the potential of biomimetic collagen scaffolds as wound dressings for dermal tissue regeneration and skin repair.<\/jats:p>","DOI":"10.1002\/jbm.a.70104","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T09:48:57Z","timestamp":1783072137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomimetic Collagen Scaffolds Natural Cross\u2010Linking Strategies via Transglutaminase and Methylglyoxal for Skin Repair"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-3356","authenticated-orcid":false,"given":"Mina","family":"Vaez","sequence":"first","affiliation":[{"name":"Faculty of Dentistry, University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Yen","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Toronto  Toronto 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