Spatiotemporal On–Off Immunomodulatory Hydrogel Targeting NLRP3 Inflammasome for the Treatment of Biofilm‐Infected Diabetic Wounds

• DOI: 10.1002/adfm.202211811
• Publication Date: 2023-01-06T07:22:49Z
• Authors: Jun Zhou; Jiawei Mei; Quan Liu; Dongdong Xu; Xiaoli Wang; Xianzuo Zhang; Wanbo Zhu; Chen Zhu; Jiaxing Wang
• Keywords: Proinflammatory cytokine; Macrophage polarization

Abstract Biofilm‐infected diabetic wounds (BIDWs) with hyperglycemia and bacterial colonization are characterized by disordered inflammation abnormal activation of NLRP3 inflammasome, leading to sustained macrophage M1 polarization neutrophil extracellular traps (NETs) formation. An immoderate anti‐inflammatory treatment that downregulates in turn promotes the persistence biofilm infections impairs healing BIDWs. Therefore, reconciling elimination immune regulation holds promise curing Herein, a novel spatiotemporal on–off immunomodulatory therapy (SOIT) is proposed for treating BIDWs through biphasic NLRP3. Methacrylate gelatin hydrogels (Gel‐MA) incorporated graphene oxide (GO) metformin‐loaded mesoporous silicone nanospheres synthesized photo cross‐linked construct nanocomposite hydrogel (MGO@GM). First, GO nanosheets released from MGO@GM inhibit formation disrupt mature biofilms under near‐infrared irradiation. Meanwhile, activates induce macrophage‐associated proinflammatory response against biofilms. Afterward, subsequent degradation MGO@GM, metformin reduces local hyperglycemia, NLRP3, inhibits NETs Furthermore, repolarized M2 macrophages alleviate inflammatory microenvironment promote tissue regeneration. Briefly, this SOIT strategy regulates rescues impaired innate immunity facilitate anti‐infection repair, which provides new perspective future clinical