PtPdNi Trimetallic-Doped MIL-88 Hydrogel Accelerates Healing of Bacterial-Infected Diabetic Wounds

Yawen Peng,1,2,* Wenjuan Du,3,* Yating Cui,1,* Chenri Su,4 Yuyu Liu,1 Yang Bai,2 Wen Li,1 Juan Zhang,2 Xianhua Wang,4 Shihui Fu,5,6 Haiyan Zhu2 1Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Emergency, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People’s Republic of China; 4Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 5Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, 572013, People’s Republic of China; 6Department of Geriatric Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiyan Zhu, 28th Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Email [email protected] Shihui Fu, 80th Jianglin Road, Haitang District, Sanya, 572013, People’s Republic of China, Email [email protected]: Treatment of bacterial-infected diabetic wounds is still challenging due to the susceptibility to bacterial infection and oxidative stress. Therefore, a novel multifunctional platform was established for accelerating the healing of bacterial-infected diabetic wounds.Methods: PtPdNi trimetallic-doped MIL-88 (PPNM) was fabricated and anchored to polyvinyl alcohol/sodium alginate (PVA/SA) matrix for constructing PPNM-containing hydrogel (PPNM-Gel). The basic properties of PPNM were characterized by TEM, SEM, XPS, FT-IR spectra, and UV-vis spectra. Adhesive, swelling, and degradation properties of PPNM-Gel were also analyzed. In vitro biocompatibility of PPNM-Gel was determined using L929 and HUVEC-SV40 cells. In vitro antimicrobial effects of PPNM-Gel were evaluated with E. coli and S. aureus. In vivo antibacterial and wound healing evaluation of PPNM-Gel was performed in the STZ-induced diabetic SD rats, which were established by intraperitoneal injection of STZ, followed by full-thickness skin wound preparation and bacterial infection. Histological and immunofluorescence staining were used to evaluate the status of epithelization, collagen deposition and inflammation response.Results: PPNM exhibited multienzyme-like activity including POD-like, OXD-like, CAT-like, SOD-like, and NAD-like activities. PPNM-Gel demonstrated excellent tissue adhesive activity, water absorption ability, biodegradability, and biocompatibility. In vitro testing, PPNM-Gel showed obvious antibacterial ability against E. coli and S. aureus in a PPNM dose-dependent approach, and its antibacterial ability against E. coli was stronger than that against S. aureus. In the STZ-induced diabetic SD rats, PPNM-Gel effectively accelerated wound remodeling by killing pathogenic bacteria, reducing inflammation, and promoting collagen deposition.Conclusion: PPNM-Gel significantly accelerated the healing of bacterial-infected diabetic wounds in the rat model. Therefore, PPNM-Gel showed great promise for the treatment of diseases affected by bacterial infections and high ROS levels.Keywords: trimetallic nanozyme, multienzyme-like activity, hydrogel, bacterial-infected diabetic wounds