Hyaluronic acid-liposomes hybridized with HucMSC exosomes for enhanced exosomes transdermal delivery and acute skin photodamage repair

Long-term exposure to ultraviolet (UV) radiation can damage human skin, resulting in photodamage. Repairing photodamaged skin has been a major focus of research in recent years. Extensive research has shown that human umbilical cord mesenchymal stem cell-derived exosomes (Exo) possess anti-inflammatory, pro-angiogenic, and wound healing properties, holding great potential for treating skin damage. However, due to the limitations of exosomes alone, such as poor transdermal penetration, instability, and low utilization, there is an urgent need for new delivery strategies. We designed a hybrid nanovesicle (HL@Exo) by combining ultrasonic incubation with membrane extrusion to fuse Exo with HL. HL@Exo capitalizes on the advantages of liposomal carriers and the permeation-enhancing properties of hyaluronic acid to effectively facilitate transdermal delivery of Exo. The successful fusion of HL@Exo and its skin penetration were verified by methods such as fluorescent labeling, western blotting, Transwell assays, and in vivo imaging. In vitro studies on photodamaged keratinocytes and endothelial cells demonstrated HL@Exo ability to promote cell proliferation, repair, angiogenesis, and reduce inflammation. In a laser-induced skin photodamage model, HL@Exo enhanced collagen regeneration, accelerated wound healing, and demonstrated significant anti-inflammatory effects, indicating its potential as a non-invasive treatment and offering a novel strategy for the clinical application of Exo.