Affiliation:
1. Institute of Polymer Science and Engineering National Taiwan University Taipei 106319 Taiwan, Republic of China
2. Division of Neurosurgery Department of Surgery National Taiwan University Hospital and College of Medicine Taipei 100225 Taiwan, Republic of China
3. Institute of Cellular and System Medicine National Health Research Institutes Miaoli 350401 Taiwan, Republic of China
Abstract
AbstractStroke is a common disease with high mortality worldwide. The endogenous neural regeneration during the intracerebral hemorrhage (ICH) stroke is restricted by the brain cavity, inflammation, cell apoptosis, and neural scar formation. Biomaterials serving as temporary supporting matrices are highly demanded as injectable implants for brain tissue regeneration. Herein, a chitosan micellar self‐healing hydrogel (CM hydrogel) with comparable modulus (≈150 Pa) to brain, shape adaptability, and proper swelling (≈105%) is developed from phenolic chitosan (PC) and a micellar crosslinker (DPF). Two model drugs are individually packaged in the hydrophilic network and hydrophobic micelle cavities of CM hydrogel, and they feature asynchronous releasing kinetics, including a first‐order rapid release for hydrophilic drug and a zero‐order sustained release for hydrophobic drug. The dual‐drug loaded CM (CMD) hydrogel delivers two clinical drugs corresponding to the anti‐inflammatory and neurogenesis phases of the stroke to ICH rats through brain injection. The rats receiving CMD hydrogel show behavioral improvement (≈84% recovery) and balanced brain midline shift (≈0.98 left/right hemibrain ratio). Immunohistochemistry reveals neurogenesis (doublecortin‐ and nestin‐ positive cells) and evidence of angiogenesis (≈18 µm diameter vessels lined with CD31‐positive cells). The injectable CMD hydrogel offers a novel asynchronous drug delivery platform for treating ICH stroke.
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials
Cited by
3 articles.
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