Silybin-Loaded Chitosan–Gelatin Hydrogels as a Novel Strategy for MRSA-Infected Diabetic Foot Treatment: In Vitro, In Vivo, and In Silico Evidence
Journal of Polymers and the Environment, cilt.34, sa.10, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 34 Sayı: 10
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s10924-026-03962-9
- Dergi Adı: Journal of Polymers and the Environment
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, Compendex, Environment Index, Geobase, Greenfile, Natural Science Collection (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Earth, Atmospheric, & Aquatic Science Collection (ProQuest), Materials Science & Engineering Collection (ProQuest), Pharma Collection (ProQuest), Technology Collection (ProQuest)
- Anahtar Kelimeler: Chitosan, Diabetic foot, Gelatin, Hydrogel, MRSA, Silybin, Wound healing
- Çukurova Üniversitesi Adresli: Evet
Özet
Diabetic foot infections are serious complications that increase morbidity, prolong hospitalization, and elevate the risk of amputation in patients with diabetes. Methicillin-resistant Staphylococcus aureus (MRSA) remains a major causative pathogen, and its multidrug resistance significantly limits the effectiveness of conventional antibiotics, necessitating alternative therapeutic strategies. This study aimed to develop and evaluate silybin-loaded chitosan–gelatin (CS–Gel) hydrogels prepared by glutaraldehyde-mediated crosslinking for the treatment of MRSA-induced diabetic foot infections. The fabricated hydrogels (SB1 and SB2) were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), confirming successful crosslin king and silybin incorporation. In vitro studies demonstrated excellent biocompatibility and hemocompatibility, with no cytotoxic effects observed in NIH/3T3 fibroblast cells at concentrations up to 10 mg/mL. Both SB1 and SB2 hydrogels exhibited potent antibacterial activity against MRSA, producing inhibition zones of 19.7 ± 0.45 mm and 20.9 ± 0.53 mm, respectively, with antibacterial efficacy rates exceeding 85%. SEM analysis revealed marked morphological disruption of MRSA cells following treatment. Molecular docking analysis provided complementary computational support for the observed antibacterial and anti-inflammatory activities, demonstrating favorable predicted binding of silybin to MRSA-associated proteins and inflammatory mediators. Consistent with these findings, silybin-loaded hydrogels significantly reduced IL-6 and TNF-α gene expression in a dose-dependent manner. Furthermore, in vivo evaluation in an MRSA-infected diabetic foot wound model demonstrated accelerated wound closure and superior healing outcomes for both SB1 and SB2 compared with fusidic acid (Fucidin®) by day 12. These findings suggest that silybin-loaded CS–Gel hydrogels represent a promising therapeutic platform for the management of MRSA-infected diabetic foot infections.