ArticleActa biomaterialia2025
Sustained ROS scavenging and pericellular oxygenation by lignin composites rescue HIF-1α and VEGF levels to improve diabetic wound neovascularization and healing.
Article in Acta biomaterialia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Composite Hydrogel Loading Polysaccharides Derived fromBiomolecules · 2026Article
- Dynamic synergistic interplay between ovarian antioxidant defense and angiogenesis sustains high egg production in laying hens.Journal of animal science and biotechnology · 2026Article
- An In Situ Embedded B-MOF Sponge With Shape-Memory for All-in-One Diabetic Wound Therapy.Advanced healthcare materials · 2026Article
- A novel molecule ZYZ329 targeting histone methyltransferase SMYD3 suppresses pathological angiogenesis via the driven mitochondrial ROS/HIF-1α/VEGFA axis.Journal of translational medicine · 2026Article
- In situ encapsulation of Cu-MOF in wax gourd sponge for integrated smart treatment of diabetic wounds.Journal of nanobiotechnology · 2026Article
- An engineered and scalable human cell-derived extracellular matrix demonstrates advantages over recombinant collagen in biomimicry and wound healing.Frontiers in bioengineering and biotechnology · 2026Article
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Authors and funding
20 authors.
Funding
Abstract
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 post-wounding, with a higher presence of pro-healing type macrophages. Our findings demonstrate that lignosulfonate composites promote diabetic wound healing without requiring additional drugs. This highlights the potential of functionalized lignosulfonate for wound healing applications that require balanced antioxidation and controlled oxygen release. STATEMENT OF SIGNIFICANCE: The lignosulfonate composites developed in this study offer a promising solution for delayed diabetic wound healing. By effectively addressing key factors contributing to the multifaceted pathophysiology of the diabetic wounds, including impaired neovascularization, increased ROS levels, and chronic inflammation and wound proteolysis, these composites demonstrate significant potential for promoting wound repair and reducing the complications associated with diabetic wounds. The unique combination of pro-angiogenic, oxygen-releasing, ECM remodeling and antioxidant properties in these lignosulfonate-based materials highlights their potential as a valuable therapeutic option, providing a multi-pronged approach to diabetic wound healing without the need for additional drugs.
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