Background The complicated hyperglycaemic and chronic inflammation of diabetic wounds in orthopaedic surgery leads to dysregulated immune cell function and potential infection risk. Immune interventions in diabetic wounds face a possible contradiction between simultaneous establishment of the pro-inflammatory microenvironment in response to potential bacterial invasion and the anti-inflammatory microenvironment required for tissue repair. To study this contradiction and accelerate diabetic-wound healing, we developed a photocurable methacryloxylated silk fibroin hydrogel (Sil-MA) system, co-encapsulated with metformin-loaded mesoporous silica microspheres (MET@MSNs) and silver nanoparticles (Ag NPs). Results The hydrogel system (M@M–Ag–Sil-MA) enhanced diabetic-wound healing via spatiotemporal immunomodulation. Sil-MA imparts a hydrogel system with rapid in situ Ultra-Violet-photocurable capability and allows preliminary controlled release of Ag NPs, which can inhibit bacterial aggregation and create a stable, sterile microenvironment. The results confirmed the involvement of Met in the immunomodulatory effects following spatiotemporal dual-controlled release via the mesoporous silica and Sil-MA. Hysteresis-released from Met shifts the M1 phenotype of macrophages in regions of diabetic trauma to an anti-inflammatory M2 phenotype. Simultaneously, the M@M–Ag–Sil-MA system inhibited the formation of neutrophil extracellular traps (NETs) and decreased the release of neutrophil elastase, myeloperoxidase, and NETs-induced pro-inflammatory factors. As a result of modulating the immune microenvironmental, the M@M–Ag–Sil-MA system promoted fibroblast migration and endothelial cell angiogenesis in vivo, with verification of enhanced diabetic-wound healing accompanied with the spatiotemporal immunoregulation of macrophages and NETs in a diabetic mouse model. Conclusions Our findings demonstrated that the M@M–Ag–Sil-MA hydrogel system resolved the immune contradiction in diabetic wounds through spatiotemporal immunomodulation of macrophages and NETs, suggesting its potential as a promising engineered nano-dressing for the treatment of diabetic wounds in orthopaedic surgery. Graphical Abstract

Background. Bone cement spacers are widely used in two-stage revision surgeries for periprosthetic joint infection (PJI) after total knee arthroplasty. Current spacer design results in insufficient release of drugs; therefore, current spacers have low efficacy. In this study, we explored a set of alternative articular spacer using 3D printing technology. This novel spacer will increase effectiveness of revision surgery for PJI. Methods. The spacer was designed using CAD software and constructed on site using 3D-printed silicone mold during debridement surgery. We carried out a retrospective study among patients undergoing treatment using traditional static and new articular spacers. Infection control rate, bone loss, difficulty of revision surgery, knee joint range of motion, function evaluation, and subjective satisfaction of the patients in the two groups were compared. Results. Forty-two patients undergoing knee revision surgery between Jan 2014 and Nov 2019 were included in this study. Twenty-two patients were treated with static antibiotic cement spacers, whereas the other twenty patients were with treated with 3D printing-assisted antibiotic loaded articulating spacers. Patients in the articular group showed significantly lower bone loss on the femur site and tibial site compared with patients in the static group. In addition, patients in the articular group showed significantly less operation time, intraoperative blood loss, and improved knee function and patient overall satisfaction compared with patients in the static group. Conclusions. The 3D printing-assisted articular spacer provides satisfactory range of motion during the interim period, prevents bone loss, facilitates second-stage reimplantation and postoperative rehabilitation, and results in low reinfection and complication rates.

Bacterial biofilm‐associated infections (BAIs) are the leading cause of prosthetic implant failure. The dense biofilm structure prevents antibiotic penetration, while the highly acidic and H2O2‐rich biofilm microenvironment (BME) dampens the immunological response of antimicrobial macrophages. Conventional treatments that fail to consistently suppress escaping planktonic bacteria from biofilm result in refractory recolonization, allowing BAIs to persist. Herein, a BME‐responsive copper‐doped polyoxometalate clusters (Cu‐POM) combination with mild photothermal therapy (PTT) and macrophage immune re‐rousing for BAI eradication at all stages is proposed. The self‐assembly of Cu‐POM in BME converts endogenous H2O2 to toxic ·OH through chemodynamic therapy (CDT) and generates a mild PTT effect to induce bacterial metabolic exuberance, resulting in loosening the membrane structure of the bacteria, enhancing copper transporter activity and increasing intracellular Cu‐POM flux. Metabolomics reveals that intracellular Cu‐POM overload restricts the TCA cycle and peroxide accumulation, promoting bacterial cuproptosis‐like death. CDT re‐rousing macrophages scavenge planktonic bacteria escaping biofilm disintegration through enhanced chemotaxis and phagocytosis. Overall, BME‐responsive Cu‐POM promotes bacterial cuproptosis‐like death via metabolic interference, while also re‐rousing macrophage immune response for further planktonic bacteria elimination, resulting in all‐stage BAI clearance and providing a new reference for future clinical application.

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