A joint research team led by Professors Jae Hyung Park and Changhyun Pang from the School of Chemical Engineering (lead authors: Minwoo Song, Minji Ha, and Dr. Sol Shin) has developed a core technology that enables a next-generation transdermal drug delivery system. By hierarchically integrating octopus-sucker–inspired suction cups with short microneedles, the team successfully created a highly adhesive dual-amplified transdermal patch capable of delivering large biomolecular therapeutics such as extracellular vesicles (EVs) deep into the skin uniformly, efficiently, and without pain. This innovation overcomes long-standing limitations of injection-based therapy and opens up new possibilities for applications ranging from aesthetic and anti-aging treatments to future smart healthcare platforms. The research addressed fundamental drawbacks of conventional microneedle patches, particularly pain, skin irritation, and poor adhesion.

The stratum corneum, the outermost layer of the skin, possesses a dense and protective structure that blocks the penetration of external substances, making it difficult for biological agents such as exosomes and proteins to reach the dermis via topical formulations like creams or ointments. Previous microneedle systems attempted to bypass this barrier by utilizing long needles over 600 μm, but such lengths often induced discomfort, irritation, and detachment on curved or moist skin surfaces. To overcome these challenges, the research team designed a bioinspired suction-cup microstructure that generates stable negative pressure upon simple attachment, without requiring external devices or power. By combining this suction mechanism with short microneedles under 300 μm, the researchers constructed a novel dual-amplification architecture. Once applied to the skin, the patch naturally forms microscale negative pressure within each suction chamber, enhancing conformal adhesion. Simultaneously, this negative pressure induces nanoscale opening and temporary deformation of the stratum corneum, thereby amplifying microneedle insertion efficiency and enabling the effective delivery of large biomolecules, including exosomes, into the dermal layer.

Animal studies demonstrated the superior therapeutic performance and safety of the newly developed exosome transdermal patch. Compared to conventional microneedle patches, the system increased drug delivery depth by approximately 2.6-fold (up to 290 μm). It also stimulated collagen production, reduced reactive oxygen species (ROS), and improved the microenvironment of aging skin. Importantly, the patch maintained strong, stable adhesion even on curved or moist skin surfaces, ensuring sustained drug delivery during long-term application.

The dual-amplified patch exhibits excellent biocompatibility and irritation-free delivery, making it suitable for stable daily use. Beyond exosomes, the platform can effectively deliver a wide range of biological therapeutics, including proteins and nucleic acids. Therefore, its applicability is expected to expand into diverse fields such as cosmetic dermatology, anti-aging therapy, regenerative applications, and wearable smart healthcare systems.

This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (No. RS-2023-00256265, RS-2024-00352352, RS-2024-00405818) and by the Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Health & Welfare). (No. 25A0102L1). The authors gratefully acknowledge the support from the Market-led K-sensor technology program (RS-2022-00154781, Development of large-area wafer-level flexible/stretch- able hybrid sensor platform technology for form factor-free highly integrated convergence sensor), funded By the Ministry of Trade, Industry & Energy (MOTIE, Korea).

The study was published online on July 23, 2025, in the international journal Nano-Micro Letters (IF 36.3, JCR top 1%) and was selected as the Cover Paper.

*Paper Title: A Hierarchical Short Microneedle-Cupping Dual-Amplified Patch Enables Accelerated, Uniform, Pain-Free Transdermal Delivery of Extracellular Vesicles

*Journal: Nano-Micro Letters

*Paper Link: https://doi.org/10.1007/s40820-025-01853-7

*Pure: https://pure.skku.edu/en/persons/jae-hyung-park/ (Prof. Jae Hyung Park)

              https://pure.skku.edu/en/persons/changhyun-pang/(Prof. Changhyun Pang)