Hydrogel‐based drug delivery systems for intracerebral hemorrhage with therapeutic advances and emerging roles of the bone–brain axis

Abstract Intracerebral hemorrhage (ICH) is a severe neurological condition characterized by high mortality and long‐term disability. The pathophysiology of ICH involves not only primary hematoma formation but also secondary injury mechanisms such as blood–brain barrier disruption, oxidative stress, excitotoxicity, and neuroinflammation. Hematoma‐derived factors like hemoglobin, iron, and thrombin, together with pro‐inflammatory cytokines from activated glial and immune cells, exacerbate neurovascular dysfunction. Emerging research highlights the role of the bone‐brain axis, where bone marrow‐derived cells and osteokines influence systemic inflammation, angiogenesis, and tissue repair. Hydrogel‐based drug delivery systems (HDDS) have gained attention for their potential to address these challenges, offering controlled release, biocompatibility, and targeted delivery. This review summarizes recent advancements in hydrogel‐based therapeutic strategies for ICH treatment, focusing on structure‐activity relationships and the integration of bone‐brain axis modulation for enhanced neuroregeneration. We discuss key translational barriers, including biosafety, manufacturing scalability, and inter‐patient heterogeneity. Future advances are expected to rely on the development of dynamic, microenvironment‐responsive hydrogels that can synchronize drug release with stage‐specific pathological cues, improving therapeutic precision. Moreover, combining HDDS with multimodal therapies and minimally invasive neurosurgical techniques may further enhance clinical outcomes. The potential for HDDS to target both local brain injury and systemic inter‐organ crosstalk represents a promising direction for advancing clinical applications in ICH.