Hydrogel dressings with intrinsic antibiofilm and antioxidative dual functionalities accelerate infected diabetic wound healing.

Chronic wounds are often infected with biofilm bacteria and characterized by high oxidative stress. Current dressings that promote chronic wound healing either require additional processes such as photothermal irradiation or leave behind gross amounts of undesirable residues. We report a dual-functionality hydrogel dressing with intrinsic antibiofilm and antioxidative properties that are synergistic and low-leaching. The hydrogel is a crosslinked network with tethered antibacterial cationic polyimidazolium and antioxidative N-acetylcysteine. In a murine diabetic wound model, the hydrogel accelerates the closure of wounds infected with methicillin-resistant Staphylococcus aureus or carbapenem-resistant Pseudomonas aeruginosa biofilm. Furthermore, a three-dimensional ex vivo human skin equivalent model shows that N-acetylcysteine promotes the keratinocyte differentiation and accelerates the re-epithelialization process. Our hydrogel dressing can be made into different formats for the healing of both flat and deep infected chronic wounds without contamination of the wound or needing other modalities such as photothermal irradiation.

Identification of Malassezia furfur Secreted Aspartyl Protease 1 (MfSAP1) and Its Role in Extracellular Matrix Degradation.

Malassezia is the most abundant eukaryotic microbial genus on human skin. Similar to many human-residing fungi, Malassezia has high metabolic potential and secretes a plethora of hydrolytic enzymes that can potentially modify and structure the external skin environment. Here we show that the dominant secreted Malassezia protease isolated from cultured Malassezia furfur is an aspartyl protease that is secreted and active at all phases of culture growth. We observed that this protease, herein named as MfSAP1 (M. furfur secreted aspartyl protease 1) has a broader substrate cleavage profile and higher catalytic efficiency than the previously reported protease homolog in Malassezia globosa. We demonstrate that MfSAP1 is capable of degrading a wide range of human skin associated extracellular matrix (ECM) proteins and ECM isolated directly from keratinocytes and fibroblasts. Using a 3-D wound model with primary keratinocytes grown on human de-epidermized dermis, we show that MfSAP1 protease can potentially interfere with wound re-epithelization in an acute wound model. Taken together, our work demonstrates that Malassezia proteases have host-associated substrates and play important roles in cutaneous wound healing.