Core-Shell Silk Fibroin Hydrogel Microneedles Functionalized with Antibody-Binding Domains for Transdermal Delivery

Abstract

Microneedle (MN) patches comprise a promising platform for transdermal delivery of macromolecular therapeutics. However, achieving sufficient mechanical strength for skin penetration while maintaining high biocompatibility and efficient antibody loading remains a major challenge. In this study, we designed and developed a core-shell-structured hydrogel MN patch composed of a silk fibroin core and a protein-based shell layer for antibody loading and potential transdermal release. The latter was constructed using a fusion protein consisting of the B and C domains of Staphylococcus aureus protein A (BC) and a tyrosine-rich mussel adhesive protein (MAP), thereby enabling antibody binding via the BC domains. By harnessing biomimetic design strategies, the BC-MAP shell facilitates antibody immobilization via specific affinity interactions, while the silk fibroin core provides substantial mechanical strength: the MN patch demonstrated a penetration force approximately 4.2 times greater than that required to pierce porcine skin. Collectively, our core-shell-structured hydrogel MN patch is a promising platform for transdermal antibody delivery.