Bioengineered injectable HAMA/GelMA hydrogel encapsulating exosomes loaded lycopene mitigates deoxynivalenol-induced testicular injury via apoptotic pathway modulation
Ru Feng, Ramaiyan Velmurugan, Chunfeng Li, Ying Mu, Hai‐Yan Tian, Lina Zhou, Xiaoming Cao
Abstract
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 defense, whereas reductions were noted in inflammatory mediators TNF-α and IL-1β, as well as in mitochondrial apoptosis-associated proteins, such as Cyt-c, Bax, and Caspase-3. Meanwhile, Bcl-2 expression rose, suggesting anti-apoptotic effects. These results suggest that HAMA-GelMA@Exo-Lyc represents a promising bioengineered platform for mitigating Dex-induced testicular damage by suppressing oxidative stress and modulating the apoptosis pathway.