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Tissue regeneration strategies have traditionally relied on designing biomaterials that closely mimic features of the native extracellular matrix (ECM) as a means to potentially promote site-specific cellular behaviors. However, inflammation, while a necessary component of wound healing, can alter processes associated with successful tissue regeneration following an initial injury. These processes can be further magnified by the implantation of a biomaterial within the wound site. In addition to designing biomaterials to satisfy biocompatibility concerns as well as to replicate elements of the composition, structure, and mechanics of native tissue, we propose that ECM analogs should also include features that modulate the inflammatory response. Indeed, strategies that enhance, reduce, or even change the temporal phenotype of inflammatory processes have unique potential as future pro-regenerative analogs. Here, we review derivatives of three natural materials with intrinsic anti-inflammatory properties and discuss their potential to address the challenges of inflammation in tissue engineering and chronic wounds., (© 2016 by the Society for Experimental Biology and Medicine.)