Silk fibroin bioscaffold from Bombyx mori and Antheraea assamensis elicits a distinct host response and macrophage activation paradigm in vivo and in vitro

Biomaterials composed of silk fibroin from both mulberry and non-mulberry silkworm varieties have been investigated for their utility in tissue engineering and drug delivery, but these studies have largely excluded any evaluation of host immune response. The present study compares the macrophage activation response towards mulberry (Bombyx mori, BM) and non-mulberry (Antheraea assamensis, AA) silk types, individually and as a blend (BA) in a partial thickness rat abdominal wall defect model and in vitro primary murine bone marrow-derived macrophage (BMDM) assay. Biologic materials composed of liver extracellular matrix (LECM) and small intestinal submucosa (SIS) ECM that are recognized for constructive tissue remodeling, and polypropylene mesh that is associated with pro-inflammatory macrophage phenotype activation are used as controls in the animal model. The AA silk graft shows a host response similar to SIS with few foreign body multinucleate giant cells, vascularization, high CD206 expression, and high M2-like: M1-like macrophage phenotype ratio. Exposure to AA silk degradation products in vitro induces a higher arginase: iNOS ratio in both naive BMDM and pro-inflammatory activated BMDM; and higher Fizz1: iNOS ratio in pro-inflammatory activated BMDM. These data suggest that the AA silk supports a pro-remodeling macrophage response with potential therapeutic applications.