Catalyst-Free Collagen Filament Crosslinking for Engineering Anisotropic and Mechanically Robust Tissue Scaffolds.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Engineering mechanically resilient hydrogels from naturally derived proteins, such as collagen and gelatin, remains a key challenge in tissue regeneration, particularly when cell compatibility and structural integrity are simultaneously required. Here, a bioorthogonal crosslinking strategy using rhodamine and polyethylene glycol (PEG) is reported to fabricate dense, mechanically reinforced collagen hydrogels. PEG-mediated dehydration induces spontaneous peptide bond formation between rhodamine and collagen without the need for additional catalysts, yielding fibrous protein networks with enhanced stiffness. To enable anisotropic tissue engineering, this crosslinking method is integrated with wet-spinning to produce uniaxially aligned collagen filaments. These constructs exhibit high mechanical strength and support human adipose-derived stem cell (hASC) encapsulation. Mechanotransductive signaling, including cytoskeletal organization and myogenic gene expression, is effectively activated within the aligned filaments. The applicability of cell-laden filaments in a murine volumetric muscle loss model is demonstrated, which promoted in vitro differentiation and in vivo functional muscle regeneration. This strategy offers a scalable and cytocompatible platform for generating aligned protein-based scaffolds with tunable mechanical and biological properties, thereby expanding the toolk

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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