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A significant increase in fibroblast proliferation and migration was observed in cross-linked MatriDerm with reduced scaffold contraction in vitro. In the mouse model, noncross-linked MatriDerm was almost completely biodegraded after 14 days whereas cross-linked MatriDerm remained intact. No significant difference in wound contraction was found between scaffolds. In conclusion, cross-linked MatriDerm showed a significant increase in stability and strength, enhancing its durability and cell-scaffold interaction. in vivo analysis showed c