Construction of Smart Hydrogel-Exosome Drug Delivery Platforms and Their Applications in Skin Rehabilitation

Skin rehabilitation is a highly coordinated process involving sequential cellular and molecular events that ultimately restore the integrity and function of damaged tissue, yet this cascade is frequently disrupted by infection, oxidative stress, and inflammation. Precise and controllable drug delivery is the key to enhance the efficacy of skin rehabilitation and reduce the systemic side effects. Although exosomes, as natural drug carriers, possess low immunogenicity and excellent biocompatibility, they still face challenges such as rapid in vivo clearance and insufficient targeting ability. The smart hydrogels, with their three-dimensional polymeric network structure and stimulus-responsive properties (such as pH, reactive oxygen system and glucose), can not only serve as a "reservoir" for exosomes but also act as their "intelligent switch". Therefore, the smart hydrogel-exosome platforms can enhance the efficacy of skin rehabilitation by enabling local, continuous, targeted and controllable drug release. Excitingly, by reducing secondary infection risk, enabling responsive inflammatory regulation, and preventing the tissue damage associated with frequent dressing changes, this system addresses the key limitations of conventional therapies, including topical agents, wound dressings, intralesional injections, and skin grafting. This article reviews the construction of these smart hydrogel-exosome drug delivery platforms, focusing on the sources, isolation and drug-loading strategies of exosomes, as well as the response mechanisms and fabrication strategies of the smart hydrogels. It also summarizes the mechanism and latest progress of this system in skin rehabilitation. Finally, this article looks forward to the challenges and future directions in this field, with the aim of providing new strategies for precise treatment of skin.