Self-healing hydrogel with micellar architecture for neural repair

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ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków


Lin, Shih-ho (Institute of Polymer Science and Engineering, National Taiwan University)


Injured neural tissue after the intracerebral hemorrhage (ICH) stroke has limited endogenous regeneration because of inflammation and cell apoptosis. The brain cavity and neural scar tissue caused by the hematoma often lead to a permanent behavior disability. Biomaterials can serve as temporary supporting matrices and promote brain tissue regeneration. A chitosan-based self-healing hydrogel (CM hydrogel) with micellar structure and comparable stiffness (modulus ~ 0.5 kPa) to brain tissue was developed based on modified chitosan and an aldehyde-terminated triblock copolymer crosslinker. The hydrogel network with self-healing ability was built up through Schiff-base reaction and filled with self-assembled micellar cavities (~20 nm) constructed by the hydrophobic interaction. Two model drugs with opposite affinity to water were successfully packaged (100% efficiency) in the hydrophilic network and hydrophobic cavities of the hydrogel, respectively. Such a drug delivery hydrogel showed two different releasing kinetics. The kinetics included a first-order rapid releasing tendency to the hydrophilic drug and a zero-order sustained releasing to the hydrophobic one. In the stroke model, a hydrophilic anti-inflammatory drug for short-term release and a hydrophobic neuroprotective drug for long-term release were selected in accordance with the subacute and chronic phases of stroke pathology. After 2 weeks of the hydrogel injection into the stroke rats, the scar tissue nearby the stroke cavity significantly decreased, while the signal of doublecortin, a marker from new nerve cells, was observed through immunohistochemistry staining. Magnetic resonance imaging (MRI) revealed the reduced inflammation around the brain cavity in the experimental group. The behavior performance of rats was improved after 28 d of the therapeutic period, evaluated by the rotarod test. The new self-healing hydrogel with micellar architecture offers as a novel drug delivery platform for diseases with complex time-dependent pathological stages, such as the ICH stroke.


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