Implanted and degradable hydrogel evaporative cooler for regional and repeated mild hypothermia therapy of traumatic brain injury.

Implantable, regional and repeated mild hypothermia represents a promising therapeutic strategy for traumatic brain injury. Here, we develop a soft, degradable hydrogel microchannel evaporative cooler capable of removing heat through water evaporation in microchannels and achieving focused regional cooling within a short time. Fabricated from degradable hydrogels and using water as the coolant, the cooler shows biocompatibility and tissue adhesion. In vivo intracranial experiments with the cooler adhered on the rat dura mater enabled precise temperature regulation during repeated regional hypothermia (33 ± 0.5 °C, 4 h per day for 3 consecutive days). The treatment conferred neuroprotection and supported neural repair, with therapeutic effects persisting for 14 days. Sustained recovery was associated with increased Nestin+/Ki67+ and Sox2+/Ki67+ cells, along with elevated MAP2/PSD95 co-localization. Additional staining confirmed the presence of Nestin+/GFAP- and Sox2+/GFAP- cell populations, supporting the involvement of progenitor-like cells. At 28 days post-injury, rats receiving treatment exhibited reduced lesion volume, preserved axonal integrity and myelination, and ameliorated cognitive performance. Proteomic profiling performed at day 3 further suggested that repeated hypothermia modulates synaptic plasticity, dampens neuroinflammation, and rescues perturbed energy metabolism, representing a multi-faceted response distinct from single-episode hypothermia. Collectively, these findings highlight the translational potential of this implantable cooling strategy for TBI therapy.