Sustained ROS scavenging and pericellular oxygenation by lignin composites rescue HIF-1α and VEGF levels to improve diabetic wound neovascularization and healing

作者：Jangwook P. Jung, Oluyinka O. Olutoye, Tanuj J. Prajati, Olivia S. Jung, Lane D. Yutzy, Kenny L. Nguyen, Stephen W. Wheat, JoAnne Huang, Benjamin Padon, Fayiz Faruk, Sonya S Keswani, Phillip Kogan, Aditya Kaul, Ling Yu, Hui Li, Shiyanth Thevasagayampillai, Mary E. Guerra, Walker D. Short, Preethi H. Gunaratne, Swathi Balaji · 发表于：Acta Biomaterialia · 年份：2025 · DOI：10.1016/j.actbio.2025.04.047 · 被引用次数：13 · 研究领域：Wound Healing and Treatments、Mesenchymal stem cell research、Advanced Glycation End Products research

Although delayed wound healing is an important clinical complication in diabetic patients, few targeted treatments are available, and it remains a challenge to promote diabetic wound healing. Impaired neovascularization is one of the prime characteristics of the diabetic phenotype of delayed wound healing. Additionally, increased levels of reactive oxygen species (ROS) and chronic low-grade inflammation and hypoxia are associated with diabetes, which disrupts mechanisms of wound healing. We developed lignosulfonate composites with several wound healing properties, including sustained oxygen release through calcium peroxide nanoparticles and ROS and free radical scavenging by thiolated lignosulfonate nanoparticles. Sustained release of oxygen and ROS-scavenging by these composites promoted endothelial cell (EC) branching and characteristic capillary-like network formation under high glucose conditions in vitro. Gene co-expression network analysis of RNA-sequencing results from ECs cultured on lignin composites showed regulation of inflammatory pathways, alongside the regulation of angiogenic hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth facor (VEGF) pathways. In vivo, lignosulfonate composite treatment promoted VEGF expression and angiogenesis in full thickness skin wounds in diabetic (db/db) mice, a model of delayed wound healing. Lignosulfonate composites also promoted faster epithelial gap closure and increased granulation tissue deposition by day 7 p...