Vertically Aligned Micro- and Nanoneedles for Advanced Biomedical Applications: From Fabrication Strategies to Clinical Translation

Abstract

Effective therapeutic delivery and diagnostic monitoring at cellular levels are constrained by biological barriers including stratum corneum, extracellular matrix, and plasma membranes. Conventional approaches such as viral vectors and liposomes face limitations including inadequate penetration, immunogenicity, and invasiveness. High-aspect-ratio nanostructures, including nanoneedles and microneedles, address these challenges through their unique geometries enabling direct, minimally invasive cellular access. This review examines high-aspect-ratio nanostructure technologies from fabrication strategies to therapeutic and diagnostic applications. We discuss bottom-up synthesis, top-down lithographic methods, and integrative approaches enabling precise control over geometry, mechanical properties, and surface functionalization. Mechanotransduction applications reveal how these architectures modulate cellular behavior through mechanosensitive pathways and enable phenotypic control. Recent advances have expanded applications to precision medicine through intracellular delivery of genetic engineering tools to challenging cell populations including immune cells and neurons. Hollow, porous, and surface-functionalized architectures enable controlled therapeutic release and targeted cellular reprogramming. Diagnostic applications demonstrate capabilities for intracellular sensing and continuous physiological monitoring. Convergence with artificial intelligence promises adaptive, personalized therapeutic protocols. However, challenges including scalable manufacturing, long-term biocompatibility, and regulatory translation must be addressed to realize clinical potential. This review positions high-aspect-ratio nanostructures as foundational platforms for next-generation precision medicine and personalized healthcare.