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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).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The hydrogel system (M@M\u2013Ag\u2013Sil-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\u2013Ag\u2013Sil-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\u2013Ag\u2013Sil-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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings demonstrated that the M@M\u2013Ag\u2013Sil-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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12951-022-01414-9","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T13:03:34Z","timestamp":1652533414000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":108,"title":["An injectable photo-cross-linking silk hydrogel system augments diabetic wound healing in orthopaedic surgery through spatiotemporal immunomodulation"],"prefix":"10.1186","volume":"20","author":[{"given":"Jiawei","family":"Mei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingtong","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,14]]},"reference":[{"issue":"11","key":"1414_CR1","doi-asserted-by":"publisher","first-page":"3653","DOI":"10.1002\/jps.24610","volume":"104","author":"J Boateng","year":"2015","unstructured":"Boateng J, Catanzano O. 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