Research advances on protein-based microneedles for treatment of skin diseases: A review

Protein-based microneedles (MNs) have emerged as a minimally invasive platform for transdermal therapy, enabling precise and localized delivery of bioactive molecules to cutaneous lesions. This review provides a comprehensive overview of protein-based MN systems, including key matrix materials, fabrication strategies, and their therapeutic applications across a wide range of skin diseases. Natural proteins such as gelatin, silk fibroin, zein, and collagen, are widely employed in MN fabrication due to their favorable physicochemical properties, including excellent biocompatibility, biodegradability, and tunable mechanical strength. These materials support mild drug encapsulation and efficient transdermal delivery, while their intrinsic bioactivity-such as pro-regenerative and biointeractive functions-can further enhance therapeutic outcomes through synergistic effects. Recent advances in protein-based MNs have demonstrated significant potential in the treatment of inflammatory skin diseases, wound healing, melanoma, and cosmetic dermatology. However, several challenges remain, including limited long-term stability, batch-to-batch variability, and the high cost of large-scale sterile manufacturing, which hinder clinical translation. In addition, regulatory complexity associated with device-drug combination products presents further barriers to commercialization. Future research is expected to focus on the development of stimuli-responsive and theranostic MN systems, as well as scalable, reproducible, and sustainable manufacturing strategies. Overall, protein-based MNs represent a versatile and promising platform for next-generation dermatological therapies, with strong potential for clinical translation and commercial development.