Bioinspired Microneedles for Multifunctional Theranostics: Design Principles, Fabrication Strategies, and Translational Barriers

Abstract Bioinspired microneedles (MNs) are rapidly evolving into advanced, minimally invasive platforms for transdermal drug delivery and diagnostics, driven by the growing demand for multifunctional, patient-centric theranostic systems. However, the integration of multiple therapeutic and diagnostic modalities within a single MN architecture remains a significant challenge owing to the conflicting requirements of mechanical penetration, anchoring stability, biofluid transport, and long-term functional reliability. Bioinspiration offers a coherent, transformative framework for addressing these bottlenecks by translating structural, interfacial, and adaptive strategies evolved in natural systems into engineered designs. This review systematically examines biomimetic MN architectures that enable optimized skin access, asymmetric tissue anchoring, and efficient biofluidic transport, highlighting how these features provide the structural requirements for multifunctional operation. Recent advances in fabrication technologies, including high-resolution additive manufacturing, magnetic and dynamic field-assisted assembly, and four-dimensional printing, are discussed as key enablers for implementing complex bioinspired geometries and spatially programmed functionalities. Complementary material selection strategies, encompassing high-performance polymers, hydrogels, biocomposites, and stimuli-responsive materials, are analyzed for their roles in preserving mechanical fidelity, enabling dynamic adhesion, and supporting active therapeutic and diagnostic functions. Building on these foundations, we critically review multifunctional theranostic MN platforms integrating synergistic drug delivery, embedded biosensing, and autonomous functional sequencing, alongside key translational considerations such as insertion reliability, dosing fidelity, and multicomponent stability. Collectively, this review positions bioinspired multifunctional MN patches as a promising pathway toward robust, adaptive, and clinically viable transdermal theranostic systems.