Spermidine-functionalized biomaterials to modulate implant-induced immune response and enhance wound healing

Medical implants often induce foreign body reaction (FBR) from the host immune system, which may cause implant failure. Spermidine is a natural polyamine with various important functions, especially in immunomodulation. Herein, two types of spermidine-functionalized biomaterials have been fabricated: one is hydrogels from natural biopolymers and the other is composite films based on synthetic polymers. Both spermidinefunctionalized hydrogels and films can inhibit inflammatory responses of macrophages and favor the polarization toward M2 phenotype in vitro. More importantly, both spermidine-functionalized biomaterials downregulate pro-inflammatory cytokines in rats and accelerate the transition from M1 macrophage-dominated phase to M2 macrophage-dominated phase, leading to faster and more natural wound healing. An "operando" proteomic analysis has yielded interesting hits that suggest possible mechanisms to explain our in vivo observations and the recent reports about spermidine. Hence, the local administration of spermidine in medical implants may afford a more natural and elegant way to mitigate implant-induced inflammation and foreign body reaction.