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Doxycycline Loaded Collagen-Chitosan Composite Scaffold for the Accelerated Healing of Diabetic Wounds
Published on: August 21, 2021
Dual-functional quaternized chitosan-modified carbon dots within a polymeric fiber-gel scaffold for infected wound
Yuanyuan Geng1, Fangman Chen1, Yanteng Xu1
1Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Abstract:
While polysaccharide-based biomaterials show great promise in wound management, endowing them with potent, antibiotic-free antibacterial and immunomodulatory properties remains a profound challenge. Herein, we report the functionalization of aspirin-derived carbon dots with a bioactive carbohydrate derivative, quaternized chitosan, via a one-step hydrothermal synthesis, yielding a novel dual-functional macromolecular conjugate (CS-ACD). Leveraging the strong polycationic properties of the modified carbohydrate, CS-ACD achieves a remarkable 97.3% sterilization rate against E. coli through physical membrane lysis, inherently circumventing drug resistance. Concurrently, the entire macromolecular conjugate acts as a potent immunomodulator, driving macrophage reprogramming from a pro-inflammatory M1 to a reparative M2 phenotype. This shift significantly reduces TNF-α expression (9.85-fold) while elevating M2 markers (13.59-fold). To optimize clinical translation, we integrated this carbohydrate-functionalized conjugate into a sandwich-structured electrospun nanofiber/fibrin gel polymeric composite. This scaffold provides hemostasis, optimal gas exchange, and sustained localized release. In an E. coli-infected murine wound model, the composite drastically reduced bacterial burdens (15.26-fold) and accelerated tissue regeneration, leaving only ~1.0% residual wound area by day 13. By coupling targeted polysaccharide functionalization with an advanced polymeric scaffold, this work presents a highly translatable, carbohydrate-based strategy for treating infected wounds.
