Sustained ROS Scavenging and Pericellular Oxygenation by Lignin Composites Rescue HIF-1α and VEGF Levels to Improve Diabetic Wound Neovascularization and Healing

Abstract

Although delayed wound healing is an important clinical complication in diabetic patients, few targeted treatments are available, and it remains challenging 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 disrupt mechanisms of wound healing. We developed lignin composites with multiple wound healing-promotive functions, including pro-angiogenesis, sustained oxygenation from calcium peroxide based nanoparticles and ROS scavenging with thiolated lignosulfonate that captures the elevated ROS in diabetic wounds. The sustained release of oxygen and ROS-scavenging lignin composites promoted endothelial cell branching and their reorganization into characteristic network formation in vitro, and promoted vascular endothelial growth factor (VEGF) expression and capillary lumen formation in full thickness skin wounds in a diabetic murine model of delayed wound healing (db/db), with decreased HIF-1alpha expression. These effects significantly increased the granulation tissue deposition and tissue repair. Our findings demonstrate that lignin composites promote diabetic wound healing without use of other drugs and show the potential of functionalized lignosulfonate for wound healing applications requiring balanced antioxidation and controlled oxygen release.

Bioactive and Hemocompatible PLA/Lignin Bio-Composites: Assessment of In Vitro Antioxidant Activity for Biomedical Applications

“…20 By scavenging the free radicals, antioxidant biomaterials can prevent the oxidative process, promoting tissue regeneration. 21,22 However, the previous reports on lignin/PLA as an antioxidant only evaluated the cytocompatibility or antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) or other assays without providing a detailed assessment of lignin/PLA in vitro antioxidant activity. 23,24 Moreover, the development of biomaterials like tissue engineering scaffolds, stents, implants, and so forth necessitates the achievement of desired mechanical properties.…”

“…ROS interferes with cellular equilibrium, damages cellular components , which eventually causes cell apoptosis . By scavenging the free radicals, antioxidant biomaterials can prevent the oxidative process, promoting tissue regeneration. , However, the previous reports on lignin/PLA as an antioxidant only evaluated the cytocompatibility or antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) or other assays without providing a detailed assessment of lignin/PLA in vitro antioxidant activity. , …”