Click-Engineered Carbon Dots Remodel the Inflammatory Microenvironment to Accelerate Healing of Infected Diabetic Wounds

Chronic diabetic wounds continue to impose a forbidding challenge, as persistent bacterial colonization and cytokine-steered inflammatory milieu that disrupt the intrinsic progression of healing. This microenvironment hampers re-epithelialization, granulation tissue formation, and neovascularization, leaving the wound caught in a vicious cycle of inflammation and tissue damage. Herein, we report click-engineered carbon dot designed to intercept infection and inflammation in nondiabetic, diabetic, and infected diabetic wound models. Pristine carbon dots (Pn-CDs) were synthesized via hydrothermal carbonization and subsequently functionalized through Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) to yield triazole-functionalized carbon dots (Tz-CDs). Structural and spectroscopic characterization confirmed the successful incorporation of 1,2,3-triazole moieties on the carbon dot surface while preserving the structural integrity of the nanoscale carbon core. The aromatic and chemically robust 1,2,3-triazole scaffold with multiple hydrogen-bond-accepting nitrogen atoms and hydrolytic stability, promotes interfacial interactions with biological targets, thereby enhancing the therapeutic capability of the functionalized nanomaterial. Consequently, Tz-CDs achieved a 2-fold reduction in the minimum inhibitory concentration (MIC = 62.5 μg mL–1) and exhibited potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Beyond antimicrobial efficacy, the nanoplatform modulated the wound immune environment by regulating the temporal expression of inflammatory cytokines, thereby restoring immune homeostasis. This reestablished cytokine equilibrium together with enhanced angiogenic signaling, reflects the immunomodulatory and regenerative potential of Tz-CDs, accompanied by preserved structural integrity in the regenerated wound bed. Collectively, these findings highlight triazole-engineered carbon dots as promising multifunctional nanotherapeutics for chronic infected diabetic wound management.