[The Ocean University of China Zhao Xia Research Group] Seaweed Polysaccharide Photodynamic Thermosensitive Hydrogel Accelerates Healing of Infected Wounds

BZ Oligo 1 /acsami.2c23321 .

[The Ocean University of China Zhao Xia Research Group] Seaweed Polysaccharide Photodynamic Thermosensitive Hydrogel Accelerates Healing of Infected Wounds

Are you still troubled by the prolonged skin wound infection? Recently, the team of Professor Zhao Xia from the School of Medicine, Ocean University of China, based on the good biocompatibility and moisturizing properties of alginic acid, developed a photodynamic thermosensitive hydrogel of seaweed polysaccharide, which can significantly accelerate the healing of infected wounds without the use of antibiotics. Heal without developing drug resistance. The relevant research titled " Photodynamic Alginate Zn-MOF Thermosensitive Hydrogel for Accelerated Healing of Infected Wounds " was published on " ACS Applied Materials & Interfaces " ( IF=10.383 ) on May 2 .

At present, although antibiotics have been widely used in anti-infection treatment, the abuse of antibiotics can easily lead to the development of drug-resistant strains, which is not conducive to wound healing. Photodynamic therapy ( PDT ) is a recently emerging new antibacterial method that is not prone to drug resistance. It can stimulate cells to produce reactive oxygen species ( ROS ) at specific wavelengths and induce bacterial death through oxidative stress. However, most commonly used photosensitizers are hydrophobic or negatively charged, and are easily repelled by the same negatively charged cell membrane, which will reduce the accumulation of ROS in cells and affect their antibacterial effect.

Based on the above background, this study used the zinc ion organometallic framework ( Zn-MOF ) to load the photosensitizer chlorin ( Ce6 ) and compound it with alginic acid and poloxamer ( F127 ) to prepare a photodynamic thermosensitive hydrogel ( Ce6@MOF-Gel , Figure 1a ). The porous structure of Zn-MOF can realize the effective loading of Ce6 and the responsive and sustained release of Zn 2+ in the slightly acidic environment of the wound . Zn 2+ can significantly promote the healing of infected wounds by binding to the negatively charged cell membrane, increasing the accumulation of Ce6 inside the bacteria and the production of ROS ( Figure 1b ). At body temperature, Ce6@MOF-Gel can transform from a sol to a gel state, which can meet the needs of wounds of different shapes. Moreover, Ce6@MOF-Gel can obviously generate ROS under 660 nm laser irradiation ( Figure 2 ), which is conducive to exerting the photothermal antibacterial effect.

Figure 1 : Schematic diagram of the preparation of Ce6@MOF-Gel and the treatment of skin infection wounds. ( a ) Preparation method of Ce6@MOF-Gel . ( b ) After Ce6@MOF-Gel was applied to the infected wound, the MOF dissociated and released Zn 2+ in the slightly acidic environment of the wound . Zn 2+ binds to the negatively charged cell membrane, destroys the permeability of the cell membrane, and increases the internalization of the photosensitizer Ce6 . Ce6 generates ROS under laser irradiation ( 660 nm ) , which leads to oxidative stress inside the bacteria, which in turn leads to the death of the bacteria.

Figure 2 : Morphological observation and performance characterization of hydrogel ( a ) SEM image of the gel and the distribution of MOFs in the hydrogel (yellow arrow: MOFs ); ( b ) storage modulus of Ce6@MOF-Gel The change of G' and loss modulus G'' with temperature; ( c ) the strain curve of the gel, the scanning range is 0.1-100% ; ( d ) the ROS production of the gel.

The team found that Ce6@MOF-Gel can achieve similar antibacterial activity to the positive control penicillin under laser irradiation ( Figure 3a-b ). However, after 3 passages in the penicillin group , the time required for the bacteria to reach the logarithmic growth phase was significantly shortened, indicating that obvious drug resistance had occurred; while in the Ce6@MOF-Gel treatment group, after 6 passages , the time for bacteria to reach the logarithmic growth phase remained stable ( Fig. 3c ), indicating that Ce6@MOF-Gel is not easy to develop drug resistance. Moreover, Ce6@MOF-Gel can significantly inhibit the growth of antibiotic-resistant bacteria under laser irradiation ( Fig. 3d ). In addition, during the treatment of Ce6@MOF-Gel , it was found that there was obvious damage and rupture of the cell membrane, which caused the leakage of the bacterial content and eventually led to the death of the bacteria ( Fig. 3e ). This may be related to the electrostatic interaction between Zn 2+ and the cell membrane, and the damage to the bacterial membrane caused by the ROS generated by the photosensitizer Ce6 .

Figure 3 : Study on the in vitro antifungal effect and antibacterial mechanism of Ce6@MOF-Gel . ( a ) Representative photos of Staphylococcus aureus colonies; ( b ) Quantitative analysis of gel antibacterial effect; ( C ) Changes in the time required for bacteria to reach the logarithmic growth phase after passage in the gel treatment group; ( d ) Growth of antibiotic-resistant bacteria in the gel; ( e ) TEM and SEM of Staphylococcus aureus (yellow arrow: broken cell membrane)

The team established a rat model of Staphylococcus aureus infection and found that Ce6@MOF-Gel could completely heal the rat's wound on day 13 ( Figure 4 ). Further evaluation of wound healing progress by H&E staining and Masson staining showed that Ce6@MOF-Gel could significantly reduce wound inflammation, promote angiogenesis, collagen deposition and wound re-epithelialization, thereby significantly accelerating the healing of infected wounds. healing process.

Figure 4 : In vivo anti-wound effect of Ce6@MOF-Gel on full-thickness skin infection. ( a ) Schematic diagram of animal model construction and administration of full-thickness skin infection; ( b ) representative images of wound healing at different times and with different materials; ( c ) quantitative analysis of wound area; ( d ) images of bacterial infection at the wound site on day 13 and ( e ) Quantitative analysis; ( f ) Gram staining images of rat wounds in different treatment groups on day 13 .

In summary, this study based on the strategy of combining  organometallic framework ( Zn-MOF ) and photodynamic therapy ( PDT ), successfully prepared a seaweed polysaccharide photodynamic thermosensitive hydrogel ( Ce6@MOF-Gel ). Ce6@MOF-Gel exerts antibacterial effect mainly through the combination of destruction of bacterial cell membrane and ROS generated by PDT , effectively avoiding the emergence of bacterial drug resistance. The seaweed polysaccharide hydrogel has the obvious effect of promoting the healing of infected wounds, and has obvious advantages compared with the commercially available alginate wound dressing positive control. This study provides new ideas for the treatment of anti-drug-resistant bacterial infections and the development of new wound dressings from marine polysaccharides.

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