The secondary injuries following traumatic spinal cord injury (SCI) is a multiphasic and complex process that is difficult to treat. Although methylprednisolone (MP) is the only available pharmacological regime for SCI treatment, its efficacy remains controversial due to its very narrow therapeutic time window and safety concerns associated with high dosage. In this study, we have developed an oil-in-gel type of organohydrogel (OHG) in which the binary oleic-water phases coexist, for the local delivery of MP. This new OHG is fabricated by a glycol chitosan/oxidized hyaluronic acid hydrophilic network that is uniformly embedded with a biocompatible oil phase, and it can be effectively loaded with MP or other hydrophobic compounds. In addition to spatiotemporally control MP release, this biodegradable OHG also provides a brain tissue-mimicking scaffold that can promote tissue regeneration. OHG remarkably decreases the therapeutic dose of MP in animals and extends its treatment course over 21 d, thereby timely manipulating microglia/macrophages and their associated with signaling molecules to restore immune homeostasis, leading to a long-term functional improvement in a complete transection SCI rat model. Thus, this OHG represents a new type of gel for clinical treatment of secondary injuries in SCI.
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