Light-triggered theranostic hydrogels for real-time imaging and on-demand photodynamic therapy of skin abscesses

• Published in: Acta biomaterialia 2023-01, Vol.155, p.292-303
• Main Authors: Ran, Pan, Xia, Tian, Zheng, Huan, Lei, Fangmei, Zhang, Zhanlin, Wei, Junwu, Li, Xiaohong
• Format: Article
• Language: English
• Subjects: Abscess; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacteria; Humans; Hydrogels - pharmacology; Hydrogels - therapeutic use; Injectable hydrogel; Phenolsulfonphthalein; Photochemotherapy; Photodynamic therapy; Precision Medicine; Reactive Oxygen Species; Staphylococcal Infections - drug therapy; Theranostic wound dressing; Visual imaging; Wound Infection
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2022.11.039

The management of wound infection remains the major challenges in real-time diagnosis, effective bacterial elimination and rapid wound healing. Herein, we developed injectable theranostic hydrogels to achieve long-term visual imaging of infected wounds and possible infection recurrence and to launch an on-demand bactericidal effect without using any antibiotics. Antimicrobial peptide ε-polylysine (ePL)-derived hydrogels were prepared through the copolymerization of methacrylated ePL (mPL) and the conjugates with tetrakis(4-carboxyphenyl) porphyrin (mPL-TCPP) and phenol red (mPL-Pr). Light illumination of mPL-TCPP produces reactive oxidative species (ROS) to initiate free radical crosslinking into PL@Pr-TCPP hydrogels without using any additional photoinitiators and concurrently exhibits antibacterial photodynamic therapy (PDT). PL@Pr-TCPP hydrogels experience quick color changes from yellow to orange and finally to red when pH values change from 5.0 to 9.0. The actual pH and related bacterial levels in the wounds could be read from G/B signal ratios of hydrogel colors captured by a smart phone. The conjugation of phenol red and TCPP into hydrogels affords a robust bacterial infection diagnosis and persistent bactericidal effect after cycled light illumination. The bacterial capture by ePL hydrogels strengthens PDT effect through alleviating the short lifetime and action distance of ROS. On a Staphylococcus aureus-infected abscess model, light illumination of the pregel solutions achieves in situ formation of hydrogel dressings. The synergistic bactericidal performance significantly relieves inflammatory status, accelerates collagen deposition, and promotes neovascularization, leading to full recovery of the infected wounds with regeneration of skin accessories. PL@Pr-TCPP hydrogels on the wound bed show color changes upon the recurrence of bacterial infection, which could also be totally eliminated after light illumination. Therefore, this study demonstrates a feasible strategy to develop theranostic hydrogel dressings for life-cycle diagnosis and on-demand treatment of wound infections. Over 30% of skin and soft tissue infections become chronic even after appropriate antibacterial treatment, and recurrent infections are commonly reported after initial infection. Challenges remain in the development of theranostic wound dressings having the capability of point-of-care diagnosis, life-cycle monitoring and on-demand elimination of bacterial infection. Herein