Engineering electrospun living nanofibers for oral therapeutics

Living nanofibers (LNs) are biohybrid fibrous materials that integrate living microorganisms within electrospun polymeric architectures, preserving their biological activity and enabling programmed therapeutic action at the target site. Their rational design requires integrating materials science and process engineering with biological constraints, using architectures that decouple and coordinate the protection, release, and host interaction of the encapsulated microorganisms. LNs can further incorporate conventional therapeutic agents, including small-molecule drugs, peptides, and biologics, enabling combinatorial strategies in which living or bioactive components act synergistically with drug-based therapies. In this review, we discuss the fundamental principles guiding LNs design, including material and strain selection, electrospinning-based fabrication techniques, and approaches to preserve viability and functionality during processing and storage. We then examine the physicochemical and biological barriers to oral delivery, including gastric acidity, enzymatic degradation and mucosal and epithelial barriers, and highlight emerging strategies to overcome these limitations. Finally, we discuss current and prospective applications of LNs in gastrointestinal and oncological therapies, emphasizing current capabilities for site-directed release and the requirements that remain for responsive therapeutic behaviour.