Mimicking gingival endotoxin tolerance to modulate immune balance for tumor postoperative wound management

Abstract

Postoperative management after tumor resection poses a significant clinical challenge as it must satisfy two demands – tumor eradication and tissue repair, which require contradictory immunological characteristics. Current treatment strategies have limitations as they usually fulfil one of the two requirements. Here, inspired by the unique mechanism of bacteria-triggered endotoxin tolerance (ET) in maintaining tissue homeostasis in the periodontal tissue, we devise a bioactive scaffold to establish an ET-mimicking immune niche in the local tissue of tumor resection. This glucomannan derivative-based electrospun scaffold (GMES) efficiently stimulates macrophages towards an ET state via a toll-like receptor-2 (TLR2)-dependent manner that, on the one hand, overexpresses pro-inflammatory factors and macrophage receptor with collagenous structure (MARCO) to suppress tumor recurrence and, on the other hand, release anti-inflammatory and pro-regenerative factors to promote wound healing. Our in vivo tests in three models of tumor recurrence, post-resection wounds and tumor metastasis show that GMES promotes healing at the tumor resection site while preventing tumor recurrence or metastasis. Our strategy represents a novel, microbial signal-inspired approach to postoperative tumor management.