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Due to the complex microenvironment and healing process of diabetic wounds, developing wound dressing with good biocompatibility, mechanical stability, breathability, exudate management, antibacterial ability, and immunomodulatory property is highly desired but remains a huge challenge. Herein, a multifunctional cryogel is designed and prepared with bio‐friendly bacterial cellulose, gelatin, and dopamine under the condition of sodium periodate oxidation. Bacterial cellulose can enhance the mechanical stability of the cryogel by improving the skeleton supporting effect and crosslinking degree. The cryogel shows outstanding breathability and exudate management capability thanks to the interpenetrated porous structures. I2 and sodium iodides produced in situ by reduction of sodium periodate provide efficient antibacterial properties for the cryogel. The cryogel facilitates macrophage polarization from M1 to M2, thus regulating the immune microenvironment of infected diabetic wounds. With these advantages, the multifunctional cryogel effectively promotes collagen deposition and neovascularization, thus accelerating the healing of infected diabetic wounds. [ABSTRACT FROM AUTHOR]

It is highly desirable yet significantly challenging to fabricate injectable, self‐crosslinked, self‐fused, and antifouling polyzwitterionic hydrogels, whose successful preparation will expand their application scope in biomedical fields. Herein, for the first time, a novel zwitterionic monomer, carboxybetaine urethane acrylate (CBUTA) is designed and synthesized with a urethane group and zwitterion on the same side chain. The strong inter‐urethane H‐bonds and zwitterionic dipole–dipole interactions of side chains contribute to self‐crosslinked wholly supramolecular polyzwitterionic hydrogel that is directly formed from photoinitiated polymerization of CBUTA aqueous solution without adding any chemical crosslinkers. After being swollen in water, the polyCBUTA (PCBUTA) hydrogel is squeezed into small particles and freeze‐dried to obtain hydrogel powder. The injectable and wholly zwitterionic supramolecular PCBUTA hydrogel can be easily reconstructed by mixing hydrogel powder with water due to the recombination of H‐bonds of urethane groups and zwitterionic dipole–dipole interactions. The re‐formed PCBUTA hydrogel exhibits an excellent self‐fused and antifouling ability, and this injectable PCBUTA hydrogel, endowed with a microenvironment‐regulated function, demonstrates excellent glucose consumption, antioxidation, antibacterial, and angiogenesis ability, thus accelerating the infected diabetic wound healing. Overall, this work provides a promising strategy to develop injectable and wholly zwitterionic hydrogels that will find broad biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract Due to the complex microenvironment and healing process of diabetic wounds, developing wound dressing with good biocompatibility, mechanical stability, breathability, exudate management, antibacterial ability, and immunomodulatory property is highly desired but remains a huge challenge. Herein, a multifunctional cryogel is designed and prepared with bio‐friendly bacterial cellulose, gelatin, and dopamine under the condition of sodium periodate oxidation. Bacterial cellulose can enhance the mechanical stability of the cryogel by improving the skeleton supporting effect and crosslinking degree. The cryogel shows outstanding breathability and exudate management capability thanks to the interpenetrated porous structures. I2 and sodium iodides produced in situ by reduction of sodium periodate provide efficient antibacterial properties for the cryogel. The cryogel facilitates macrophage polarization from M1 to M2, thus regulating the immune microenvironment of infected diabetic wounds. With these advantages, the multifunctional cryogel effectively promotes collagen deposition and neovascularization, thus accelerating the healing of infected diabetic wounds.

Abstract Background Diabetic wound healing remains a challenge because of its susceptibility to drug-resistant bacterial infection and its persistent proinflammatory state. Switching from proinflammatory M1 macrophages (Mφs) to proregenerative M2 dominant Mφs in a timely manner accelerates wound healing by coordinating inflammatory, proliferative, and angiogenic processes. Methods We propose a sequential photothermal antibacterial and subsequent M2 Mφ polarization strategy based on nanofibers (NFs) consisting of polydopamine (PDA) coating on curcumin (Cur) nanocrystals to treat Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds. Results The PDA/Cur NFs showed excellent photothermal conversion and antibacterial effects due to the PDA shell under laser irradiation, consequently resulting in the release of the inner Cur with the ability to promote cell proliferation and reinforce the M2 Mφ phenotype in vitro. In vivo studies on MRSA-infected diabetic wounds showed that PDA/Cur NFs not only inhibited MRSA infection but also accelerated the wound regeneration process. Furthermore, the NFs displayed the ability to promote the M2 Mφ phenotype with enhanced collagen deposition, angiogenesis, and cell proliferation. Conclusion Overall, the NFs displayed great potential as promising therapeutics for healing infected diabetic wounds through a sequential photothermal antibacterial and M2 Mφ polarization strategy. Graphical abstract

The main challenges of chronic wounds represented by diabetic wounds are that the infection is not easily controlled and the healing is difficult, mainly due to the high-glucose microenvironment, M1 macrophage aggregation, and persistent inflammation. Previous studies inspired by endogenous electric fields have demonstrated that conductive materials can promote cell proliferation, migration, etc., to promote wound healing. However, no study has been conducted on the effect of conductive materials on local immunity. To this end, this study designed a graphene oxide-based conductive hydrogel to repair infected diabetic wounds. Self-healing injectable conductive hydrogels were synthesized by dynamic Schiff-base reaction and electrostatic interactions between oxidized hyaluronic acid, N-carboxyethyl chitosan, graphene oxide, and polymyxin B. The study found that the hydrogel has good biocompatibility and antibacterial properties. In addition, in vivo experiments confirmed that the hydrogel could modulate macrophage polarization to improve the local inflammatory microenvironment, promote neovascularization, and significantly accelerate the healing of diabetic wounds. Most notably, graphene oxide-based conductive hydrogels can modulate local immunity in diabetic wounds to promote healing. This study provides new guidelines for expanding research on conductive materials and new directions for promoting healing in infected diabetic wounds.

Background: Diabetic wound healing remains a challenge because of its susceptibility to drug-resistant bacterial infection and its persistent proinflammatory state. Switching from proinflammatory M1 macrophages (Mφs) to proregenerative M2 dominant Mφs in a timely manner accelerates wound healing by coordinating inflammatory, proliferative, and angiogenic processes. Methods: We propose a sequential photothermal antibacterial and subsequent M2 Mφ polarization strategy based on nanofibers (NFs) consisting of polydopamine (PDA) coating on curcumin (Cur) nanocrystals to treat Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds. Results: The PDA/Cur NFs showed excellent photothermal conversion and antibacterial effects due to the PDA shell under laser irradiation, consequently resulting in the release of the inner Cur with the ability to promote cell proliferation and reinforce the M2 Mφ phenotype in vitro. In vivo studies on MRSA-infected diabetic wounds showed that PDA/Cur NFs not only inhibited MRSA infection but also accelerated the wound regeneration process. Furthermore, the NFs displayed the ability to promote the M2 Mφ phenotype with enhanced collagen deposition, angiogenesis, and cell proliferation. Conclusion: Overall, the NFs displayed great potential as promising therapeutics for healing infected diabetic wounds through a sequential photothermal antibacterial and M2 Mφ polarization strategy. [ABSTRACT FROM AUTHOR]

• A composite hydrogel platform inspired by natural elements with a high degree of biocompatibility. • Silk fibroin hydrogel with dual functions of anti-bacterial biofilm infection and macrophage immunomodulation. • In vivo validation achieved based on infected diabetic mouse model. Infected diabetic wounds (IDW) are difficult to heal and lead to serious complications such as amputation. Inspired by natural elements, we developed an injectable photocurable hydrogel platform based on methacrylamide silk fibroin, encapsulated with ZnO NPs and plants derived fisetin, for accelerating IDW healing. The combined release of ZnO NPs and fisetin inhibited the biofilm formation of Staphylococcus aureus on the wound surface, while fisetin possessed the immunomodulatory function of promoting macrophage M2 polarization and the release of anti-inflammatory cytokines to promote tissue healing. Therefore, this natural hydrogel composite platform can be applied as a potential wound dressing with good biocompatibility. [ABSTRACT FROM AUTHOR]

The mechanisms of accelerating infected diabetic wound healing of graphene oxide-based injectable conductive hydrogel. [Display omitted] • The hydrogel exhibited excellent self-healing properties, injectability, conductivity, biocompatibility, and antibacterial properties. • The synergistic antibacterial effect of chitosan and polymyxin B can effectively control the mixed infection of diabetic wounds. • Graphene oxide-based conductive hydrogels can modulate the local immunity of diabetic wounds to accelerate the healing of diabetic wounds. • The hydrogel can promote M2 polarization, and improve the local inflammation, and angiogenesis, accelerating the healing of diabetic wounds. The main challenges of chronic wounds represented by diabetic wounds are that the infection is not easily controlled and the healing is difficult, mainly due to the high-glucose microenvironment, M1 macrophage aggregation, and persistent inflammation. Previous studies inspired by endogenous electric fields have demonstrated that conductive materials can promote cell proliferation, migration, etc., to promote wound healing. However, no study has been conducted on the effect of conductive materials on local immunity. To this end, this study designed a graphene oxide-based conductive hydrogel to repair infected diabetic wounds. Self-healing injectable conductive hydrogels were synthesized by dynamic Schiff-base reaction and electrostatic interactions between oxidized hyaluronic acid, N -carboxyethyl chitosan, graphene oxide, and polymyxin B. The study found that the hydrogel has good biocompatibility and antibacterial properties. In addition, in vivo experiments confirmed that the hydrogel could modulate macrophage polarization to improve the local inflammatory microenvironment, promote neovascularization, and significantly accelerate the healing of diabetic wounds. Most notably, graphene oxide-based conductive hydrogels can modulate local immunity in diabetic wounds to promote healing. This study provides new guidelines for expanding research on conductive materials and new directions for promoting healing in infected diabetic wounds. [ABSTRACT FROM AUTHOR]

Infected diabetic wounds are difficult to heal due to high reactive oxygen species (ROS) concentrations and recurrent infections. Such wounds can easily deteriorate into a diabetic ulcer, a chronic diabetic complication with a very high mortality rate. Herein, we propose a combined antioxidant-antibiotic therapy based on poly(ε-caprolactone)- block -poly(glutamic acid) polymer vesicle to treat infected diabetic wounds. This was realized by in situ decoration of stable, well-dispersed ceria nanoparticles onto ciprofloxacin (CIP)-loaded polymer vesicles. These resulting CIP-loaded and ceria-decorated polymer vesicles (CIP-Ceria-PVs) exhibited high superoxide dismutase mimetic activity to inhibit superoxide free radicals (the inhibition rate reached ∼50% at an extremely low cerium concentration of 1.25 μg/mL). When the cerium content is in the range of 5-20 μg/mL, the CIP-Ceria-PVs showed the highest protective capability to normal L02 cells from damage of superoxide free radicals. In addition, the CIP-Ceria-PVs exhibited enhanced antibacterial activity (the dosage of CIP in CIP-Ceria-PVs was reduced by 25-50% compared to free CIP). In vivo treatment of infected diabetic wounds was performed on a diabetic mice model. The CIP-Ceria-PVs could effectively cure infected diabetic wounds within 14 days. Overall, a combined antioxidant-antibiotic therapy was proposed by introducing ceria nanoparticles and CIP into polymer vesicles for the treatment of infected diabetic wounds.

In the present work, we have tested the potency of iodine-loaded agar transdermal patches (5 mg/cm 2 ) for the treatment of infected diabetic wounds in the Wistar rat model. The rats were treated with the newly developed agar-iodine-potassium iodide (KI)-glycerol (AKIG) patch along with two other commercial dressings Iodoflex and Tegaderm as controls. Animals that received treatment with AKIG patches and Iodoflex showed better infection containment as compared to that with Tegaderm-covered control and exhibited complete healing. The antimicrobial property of all the patches was tested on three bacterial species- Staphylococcus aureus , Escherichia coli, and Pseudomonas aeruginosa -found in infected wounds. P. aeruginosa exhibited the highest minimum inhibitory concentration and minimum bactericidal concentration values among the three bacterial species for all the patches. The patch showed values of tensile strength, elongation, water vapor transmission rate, and swelling in the range of 34 ± 5 MPa, 51% ± 5, 2700 ± 110 g/m 2 /day, and 250% ± 25, respectively, for the agar-KI-iodine patch. The release kinetics of iodine through the agar matrix was found to follow the first-order drug release kinetics.