In situ forming and reactive oxygen species-scavenging gelatin hydrogels for enhancing wound healing efficacy

• Published in: Acta biomaterialia 2020-02, Vol.103, p.142-152
• Main Authors: Thi, Phuong Le, Lee, Yunki, Tran, Dieu Linh, Thi, Thai Thanh Hoang, Kang, Jeon Il, Park, Kyung Min, Park, Ki Dong
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Arteriosclerosis; Atherosclerosis; Biodegradability; Biodegradation; Biomaterials; Biomedical materials; Cell Death - drug effects; Collagen; Cross-linking; Crosslinking; Female; Fibroblasts - drug effects; Free Radical Scavengers - pharmacology; Free radicals; Gallic acid; Gallic Acid - chemistry; Gallic Acid - pharmacology; Gelatin; Gelatin - pharmacology; Humans; Hydrogels; Hydrogels - pharmacology; Hydrogen peroxide; Hydroxyl radicals; Injectable hydrogels; Injections; Materials Testing; Mechanical properties; Mice, Inbred C57BL; Myocardial infarction; Oxidative stress; Pathogenesis; Phenylpropionates - chemistry; Phenylpropionates - pharmacology; Polymers - chemical synthesis; Polymers - chemistry; Protective Agents - pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Regeneration; Scavenging; Swine; Time Factors; Tissue engineering; Tissue regeneration; Vascularization; Viability; Wound healing; Wound Healing - drug effects
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2019.12.009

The overexpression of reactive oxygen species (ROS) contributes to the pathogenesis of numerous diseases such as atherosclerosis, myocardial infarction, cancer, and chronic inflammation. Therefore, the development of materials that can locally control the adverse effects resulting from excessive ROS generation is of great significance. In this study, the antioxidant gallic acid-conjugated gelatin (GGA) was introduced into gelatin-hydroxyphenyl propionic (GH) hydrogels to create an injectable hydrogel with enhanced free radical scavenging properties compared to pure GH hydrogels. The modified hydrogels were rapidly formed by an HRP-catalyzed cross-linking reaction with high mechanical strength and biodegradability. The resulting GH/GGA hydrogels effectively scavenged the hydroxyl radicals and DPPH radicals, and the scavenging capacity could be modulated by varying GGA concentrations. Moreover, in an in vitro H2O2-induced ROS microenvironment, GH/GGA hydrogels significantly suppressed the oxidative damage of human dermal fibroblast (hDFBs) and preserved their viability by reducing intracellular ROS production. More importantly, the ROS scavenging hydrogel efficiently accelerated the wound healing process with unexpected regenerative healing characteristics, shown by hair follicle formation; promoted neovascularization; and highly ordered the alignment of collagen fiber in a full-thickness skin defect model. Therefore, we expect that injectable GH/GGA hydrogels can serve as promising biomaterials for tissue regeneration applications, including wound treatment and other tissue repair related to ROS overexpression. Recently, many researchers have endeavored to develop injectable hydrogel matrices that can modulate the ROS level to normal physiological processes for the treatment of various diseases. Here, we designed an injectable gelatin hydrogel in which gallic acid, an antioxidant compound, was conjugated onto a gelatin polymer backbone. The hydrogels showed tunable properties and could scavenge the free radicals in a controllable manner. Because of the ROS scavenging properties, the hydrogels protected the cells from the oxidative damage of ROS microenvironment and effectively accelerated the wound healing process with high quality of healed skin. We believe that this injectable ROS scavenging hydrogel has great potential for wound treatment and tissue regeneration, where oxidative damage by ROS contributes to the pathogenesis. [Display omitted]