Abstract: The present invention provides, in some embodiments, multi-layer silk compositions including a first layer comprising silk fibroin and keratinocytes, a second layer comprising silk fibroin and fibroblasts, a third layer comprising silk fibroin and adipocytes, and a plurality of nervous system cells, wherein at least some of the plurality of nervous system cells span at least two layers, and methods of making and using the same. In some embodiments, provided methods and compositions further include immune cells and/or endothelial cells.