Microorganism-integrated microneedles: emerging biohybrid platforms for next-generation therapeutics

The minimally invasive delivery of therapeutics across biological barriers is a major challenge in modern medicine. Microneedles (MNs) are novel platforms to address this challenge effectively. Simultaneously, the therapeutic potential of live microorganisms has been harnessed for various biomedical applications. The integration of living microorganisms with MNs has recently emerged as a promising strategy that combines minimally invasive delivery with dynamic biological functions. This review explores the integration of different microorganisms (probiotics, commensal bacteria, pathogenic and engineered bacteria, and microalgae) into MNs for various biomedical applications such as chronic skin conditions, wound dressing, cancer therapy, and intradermal vaccination. In preclinical studies, these platforms generally showed improved outcomes compared with free microorganisms, microorganism-free MNs, or conventional treatments used as controls. Furthermore, combining microorganisms with photothermal agents, sonosensitizers, antibiotics, and nanozymes can further enhance therapeutic performance. Synergistic mechanisms in these platforms - such as targeted pathogen killing, microenvironment remodeling (hypoxia alleviation and glucose consumption), and in situ generation of gases and metabolites - highlight their potential as a new class of localized therapies. Finally, the current challenges along with the future potential applications of these emerging platforms are discussed in detail.