Bioengineered injectable HAMA/GelMA hydrogel encapsulating exosomes loaded lycopene mitigates deoxynivalenol-induced testicular injury via apoptotic pathway modulation

作者：Ru Feng, Ramaiyan Velmurugan, Chunfeng Li, Ying Mu, Hai‐Yan Tian, Lina Zhou, Xiaoming Cao · 发表于：Journal of Biological Engineering · 年份：2025 · DOI：10.1186/s13036-025-00555-3 · 被引用次数：7 · 研究领域：Sperm and Testicular Function、Reproductive Biology and Fertility、Bee Products Chemical Analysis

Deoxynivalenol (Dex), a widespread mycotoxin found in contaminated cereals, induces testicular dysfunction primarily through oxidative stress, inflammation, and activation of apoptotic pathways. Lycopene (Lyc), a natural antioxidant, offers cytoprotective potential but is limited by poor aqueous solubility and instability. To address these limitations, we developed a bioengineered injectable hydrogel system composed of hyaluronic acid and gelatin methacrylate, both natural biopolymers, to encapsulate exosomes preloaded with lycopene (HAMA-GelMA@Exo-Lyc) for controlled, localized delivery. Comprehensive characterization demonstrated successful integration of HAMA-GelMA@Exo-Lyc hydrogel, evidenced by a shifted amide I band at 1643.67 cm⁻¹ and a uniform porous network of 50-150 μm. The modified hydrogel exhibited improved mechanical strength (21.8 ± 1.6 kPa), faster gelation (95 ± 8 s), and enhanced water retention (85.7 ± 3.1%) compared to the unmodified HAMA/GelMA system. In vitro, GC-1 spg cells treated with HAMA-GelMA@Exo-Lyc hydrogel exhibited enhanced viability, maintaining over 79.0 ± 0.30% cell survival at 150 µg/mL after 24 h, alongside reduced ROS levels and improved proliferative capacity compared to free Lyc. In a Dex-induced testicular injury model, HAMA/GelMA@Exo-Lyc treatment restored serum testosterone levels, improved spermatogenic architecture, and significantly reduced oxidative stress markers. Elevated levels of GSH and CAT indicated an enhanced antioxidant d...