Hydrogels are particularly suitable materials for loading drug delivery agents; their high water content provides a biocompatible environment for most biomolecules, and their cross-linked nature protects the loaded agents from damage. During delivery, the delivered substance usually needs to be released gradually over time, which can be achieved by degradable cross-linked chains. In recent years, biodegradable hydrogels have become a promising technology in new methods of disease treatment and drug delivery methods due to their many advantageous properties. This review briefly discusses the degradation mechanisms of different types of biodegradable hydrogel systems and introduces the specific applications of degradable hydrogels in several new methods of disease treatment and drug delivery methods.

Background: Brain disorders, such as glioblastoma, Alzheimer’s disease and ischemic stroke, represent formidable challenges due to the highly restrictive blood–brain barrier (BBB) and the complex pathophysiological microenvironment, which severely compromise drug delivery and therapeutic outcomes. Metal–phenolic networks (MPNs), as a class of novel hybrid materials, hold great promise for overcoming brain delivery bottlenecks and enabling precise synergistic therapy by leveraging their unique physicochemical properties. However, a comprehensive synthesis of MPN designs tailored specifically to the distinct pathological mechanisms underlying brain disorders is currently lacking. Methods: In this review, we systematically outline the foundational building blocks of MPNs and their diverse nanostructure engineering strategies. Building on this, we closely align MPN customization with the four core pathological pillars of brain diseases, thoroughly summarizing advanced design strategies and synergistic therapeutic mechanisms. Additionally, we prospectively discuss emerging innovative approaches, including the targeting of neutrophil extracellular traps (NETs) to modulate the immunosuppressive tumor microenvironment. Outlook: Finally, we critically examine the pivotal obstacles hindering the clinical translation of MPNs, particularly concerning uncertainties in long-term biosafety and in vivo metabolism, metal-specific neurotoxicity and coordination-stability-governed metal release kinetics, challenges in quality control during scalable production, and the unpredictable interference of the protein corona. Conclusions: In this review, we provide a robust theoretical foundation for the rational design of mechanism-driven MPNs, while offering forward-looking perspectives to accelerate their clinical translation from bench to bedside for the precise management of brain diseases.