Impact of Select Sophorolipid Derivatives on Macrophage Polarization and Viability

A major limitation of many biomaterials is the induction of a host response that challenges the integrity and overall efficacy of the implanted material. Emerging literature suggests that the resolution of inflammation is essential for proper healing and restoration of homeostasis. Macrophages are highly plastic immune cells that play a variety of critical roles throughout the duration of the host response. Specifically, the transition from a pro-inflammatory M1 phenotype to an antiinflammatory/wound healing M2 macrophage phenotype is a central feature in the resolution of inflammation. The long-term goal of this work is to incorporate natural or modified sophorolipids (SLs), a class of glycolipids, as novel drug-loading or bioactive coating candidates to facilitate the resolution of biomaterial-induced inflammation. Toward this goal, the diacetylated lactonic SL (L) and seven SL-esters (modified to present methyl (M), ethyl (E), propyl (P), butyl (B), pentyl (Pent), hexyl (H), or octyl (O) groups) were compared with respect to macrophage viability and phenotype to identify promising SL-esters for biomaterial applications. An initial viability screen showed that certain SL-ester structures (L, Pent, and O) have relatively higher toxicity. Macrophage phenotypic assessments also revealed that most SL-esters suppressed the M1 profile in lipopolysaccharide-stimulated macrophages (M(LPS)). However, only two SL-ester candidates (E and B) were also capable of increasing the M2 profile in M(LPS), largely by enhancing the production of vascular endothelial growth factor A. Cumulatively, these results suggest that further investigation of SL-esters E and B for facilitating biomaterial-induced inflammation resolution is warranted.