A Multifunctional Nanocomposite Hydrogel Delivery System Based on Dual‐Loaded Liposomes for Scarless Wound Healing

• Published in: Advanced healthcare materials 2024-11, Vol.13 (28), p.e2401619-n/a
• Main Authors: Xing, Danlei, Xia, Guoqing, Tang, Xudong, Zhuang, Zhiwei, Shan, Jie, Fang, Xiao, Qiu, Le, Zha, Xiaojun, Chen, Xu‐Lin
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Antioxidants - chemistry; Antioxidants - pharmacology; Apoptosis; Biocompatibility; Cell proliferation; Cell Proliferation - drug effects; Cicatrix - drug therapy; Cicatrix - pathology; Curcumin - chemistry; Curcumin - pharmacology; Down-regulation; Drug Delivery Systems - methods; Fibrosis; Free radicals; Gelatin; Glycosylation; Growth factors; Hepatocyte growth factor; HMGB1 protein; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Hydrophobicity; Inflammation; liposome; Liposomes; Liposomes - chemistry; Macrophages; Male; Mechanical properties; Medical innovations; Mice; Microenvironments; nanocomposite hydrogel system; Nanocomposites; Nanocomposites - chemistry; Oxidative stress; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells; Reactive oxygen species; scarless wound healing; Scavenging; Skin; tetrahydrocurcumin; Transforming growth factor-b; Wound healing; Wound Healing - drug effects
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202401619

Increased inflammatory responses and oxidative stress at the wound site following skin trauma impair healing. Furthermore, skin scarring places fibroblasts under severe mechanical stress and aggravates pathological fibrosis. A novel liposomal composite hydrogel is engineered for wound microenvironment remodeling, incorporating dual‐loaded liposomes into gelatin methacrylate to create a nanocomposite hydrogel. Notably, tetrahydrocurcumin (THC) and hepatocyte growth factor (HGF) are encapsulated in the hydrophobic and hydrophilic layers of liposomes, respectively. The composite hydrogel maintains porous nanoarchitecture, demonstrating sustainable THC and HGF release and enhanced mechanical properties and biocompatibility. This system effectively promotes cell proliferation and angiogenesis and attenuates apoptosis. It decreases the expression of the inflammatory factors by inhibiting the high‐mobility group box /receptor for advanced glycation end product/NF‐κB (HMGB1/RAGE/NF‐κB)pathway and increases macrophage polarization from M1 to M2 in vitro, effectively controlling inflammatory responses. It exhibits remarkable antioxidant properties by scavenging excess reactive oxygen species and free radicals. Most importantly, it effectively prevents scar formation by restraining the transforming growth factor beta (TGF‐β)/Smads pathway that downregulates associated fibrotic factors. It demonstrates strong therapeutic effects against inflammation and fibrosis in a rat skin wound model with biosafety, advancing the development of innovative hydrogel‐based therapeutic delivery strategies for clinical scarless wound therapy. The preparation of liposomes loaded with THC and HGF (Lipo@THC/HGF) utilizing the film dispersion method, then embedding the Lipo@THC/HGF into gelatin methacryloyl (GelMA) to prepare the THC/HGF@Gel by rapid photoreactive UV cross‐linking. The synergistic effects of the nanocomposite hydrogel system, including reactive oxygen species (ROS) scavenging, inflammation reduction, scarring inhibition, promotion of angiogenesis, and accelerate wound healing.