Yuan Zhixian, Zhang Wei, Wang Chang, Zhang Chuwei, Hu Chao, Liu Lu, Xiang Lunli, Yao Shun, Shi Rong, Fan Dejiang, Ren Bibo, Luo Gaoxing, Deng Jun
Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing 400038, China.
Department of Burn and Plastic Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Regen Biomater. 2024 Nov 23;12:rbae134. doi: 10.1093/rb/rbae134. eCollection 2025.
Chronic diabetic wounds present significant treatment challenges due to their complex microenvironment, often leading to suboptimal healing outcomes. Hydrogen sulfide (HS), a crucial gaseous signaling molecule, has shown great potential in modulating inflammation, oxidative stress and extracellular matrix remodeling, which are essential for effective wound healing. However, conventional HS delivery systems lack the adaptability required to meet the dynamic demands of different healing stages, thereby limiting their therapeutic efficacy. To address this, we developed an injectable, ROS-responsive HS donor system integrated within a gelatin methacryloyl (GelMA) hydrogel matrix, forming a double-network hydrogel (GelMA-ODex@RRHD). The injectability of this hydrogel allows for minimally invasive application, conforming closely to wound contours and ensuring uniform distribution. The incorporation of oxidatively modified dextran derivatives (ODex) not only preserves biocompatibility but also enables the chemical attachment of ROS-responsive HS donors. The GelMA-ODex@RRHD hydrogel releases HS in response to oxidative stress, optimizing the environment for cell growth, modulating macrophage polarization and supporting vascular regeneration. This innovative material effectively suppresses inflammation during the initial phase, promotes tissue regeneration in the proliferative phase and facilitates controlled matrix remodeling in later stages, ultimately enhancing wound closure and functional recovery. The HS released by GelMA-ODex@RRHD not only expedited the process of wound healing but also improved the biomechanical characteristics of newborn skin in diabetic mice, particularly in terms of stiffness and elasticity. This enhancement resulted in the skin quality being more similar to normal skin during the wound healing process. By aligning therapeutic delivery with the natural healing process, this approach offers a promising pathway toward more effective and personalized treatments for chronic diabetic wounds.
慢性糖尿病伤口因其复杂的微环境而带来重大治疗挑战，常常导致愈合效果欠佳。硫化氢（HS）作为一种关键的气体信号分子，在调节炎症、氧化应激和细胞外基质重塑方面显示出巨大潜力，而这些对于有效的伤口愈合至关重要。然而，传统的HS递送系统缺乏适应不同愈合阶段动态需求所需的适应性，从而限制了它们的治疗效果。为了解决这一问题，我们开发了一种整合在甲基丙烯酰化明胶（GelMA）水凝胶基质中的可注射、对活性氧（ROS）响应的HS供体系统，形成了一种双网络水凝胶（GelMA-ODex@RRHD）。这种水凝胶的可注射性允许进行微创应用，紧密贴合伤口轮廓并确保均匀分布。氧化改性葡聚糖衍生物（ODex）的加入不仅保留了生物相容性，还能实现对ROS响应的HS供体的化学连接。GelMA-ODex@RRHD水凝胶在氧化应激下释放HS，优化细胞生长环境，调节巨噬细胞极化并支持血管再生。这种创新材料在初始阶段有效抑制炎症，在增殖阶段促进组织再生，并在后期促进可控的基质重塑，最终增强伤口闭合和功能恢复。GelMA-ODex@RRHD释放的HS不仅加速了糖尿病小鼠伤口愈合过程，还改善了新生皮肤的生物力学特性，特别是在硬度和弹性方面。这种改善使得伤口愈合过程中的皮肤质量更接近正常皮肤。通过使治疗递送与自然愈合过程相匹配，这种方法为慢性糖尿病伤口更有效和个性化的治疗提供了一条有前景的途径。
