Department of Orthopedics, Orthopedics Research Institute, West China Hospital, Sichuan University, China; Trauma medical center, Department of Orthopedics surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of Orthopedics, Orthopedics Research Institute, West China Hospital, Sichuan University, China.
J Control Release. 2024 Apr;368:518-532. doi: 10.1016/j.jconrel.2024.03.002. Epub 2024 Mar 12.
Current therapeutic strategies for chronic refractory wounds remain challenge owing to their unfavorable wound microenvironment and poor skin regeneration ability. Thus far, a regimen for effective chronic refractory wounds management involves bacterial elimination, alleviation of oxidative stress, inhibition of inflammatory response, and promotion of angiogenesis. In this work, an injectable glycopeptide hydrogel based on phenylboronic acid-grafted ϵ-polylysine (EPBA) and poly (vinyl alcohol) (PVA) with pH/reactive oxygen species (ROS) dual-responsive properties was prepared, which exerted intrinsic antibacterial and antioxidant properties. ROS-responsive micelles (MIC) loaded with herb-derived Astragaloside IV (AST) are introduced into the hydrogel before gelation. Attributed to the acidic condition and oxidative stress microenvironment of wound bed, the hydrogel gradually disintegrates, and the released EPBA could help to eliminate bacterial. Meanwhile, the subsequential release of AST could help to achieve anti-oxidation, anti-inflammatory, proangiogenic effects, and regulation of macrophage polarization to accelerate chronic wound healing. In addition, the wound repair mechanism of composite hydrogel accelerating skin regeneration was assessed by RNA-sequencing, exploring a range of potential targets and pathway for further study. Collectively, this multifunctional hydrogel dressing, matching different healing stages of tissue remodeling, holds a great potential for the treatment of chronic refractory wounds.
目前,由于慢性难治性创面的不利微环境和较差的皮肤再生能力,其治疗策略仍然具有挑战性。迄今为止,有效的慢性难治性创面管理方案包括细菌消除、缓解氧化应激、抑制炎症反应和促进血管生成。在这项工作中,制备了一种基于苯硼酸接枝的 ε-聚赖氨酸(EPBA)和聚乙烯醇(PVA)的可注射糖肽水凝胶,具有 pH/活性氧(ROS)双重响应特性,具有内在的抗菌和抗氧化特性。在凝胶化之前,将载有草药衍生的黄芪甲苷(AST)的 ROS 响应胶束(MIC)引入水凝胶中。由于创面床的酸性条件和氧化应激微环境,水凝胶逐渐崩解,释放的 EPBA 有助于消除细菌。同时,AST 的后续释放有助于实现抗氧化、抗炎、促血管生成作用,并调节巨噬细胞极化,从而加速慢性伤口愈合。此外,通过 RNA 测序评估了复合水凝胶加速皮肤再生的伤口修复机制,探索了一系列潜在的靶点和途径,以进行进一步研究。总的来说,这种多功能水凝胶敷料,与组织重塑的不同愈合阶段相匹配,在治疗慢性难治性创面方面具有很大的潜力。