Advanced biomedical materials and drug delivery systems for gastrointestinal applications: current understanding and future perspectives.

The gastrointestinal (GI) tract is a major site of ulcerative, inflammatory, and neoplastic diseases. It also functions as an important interface in systemic metabolic regulation. The effectiveness of current treatments is often limited by poor drug stability and short residence times in the GI tract, insufficient exposure at the target site, and unnecessary systemic exposure. These limitations are compounded by regional pH changes, digestive enzymes, mucus turnover, peristaltic clearance, immune surveillance, and microbial metabolism. Advanced biomedical materials, including mucoadhesive hydrogels, stimuli-responsive nanoplatforms, metal-organic frameworks (MOFs), and extracellular matrix (ECM)-derived scaffolds, are increasingly being developed to protect cargo, prolong mucosal residence, enable site-selective release, support tissue repair, and modulate immune or microbial processes. However, selecting a suitable material and delivery strategy for different GI diseases remains challenging. This review examines physiological barriers to drug delivery in the GI tract, classifies advanced biomaterials and delivery systems by therapeutic function and platform type, and evaluates their applications across GI diseases with attention to administration routes, target sites, therapeutic outcomes, and clinical translation. Finally, we discuss future priorities for route-specific material design, human-relevant evaluation, and the safe development of advanced delivery systems. This review aims to provide a practical reference for selecting appropriate biomaterials and delivery systems for GI disease treatment and for guiding their further development toward clinical use.