Strongly Adhesive, Self-Healing, Hemostatic Hydrogel for the Repair of Traumatic Brain Injury.

ABSTRACT

With wide clinical demands, therapies for traumatic brain injury (TBI) are a major problem in surgical procedures and after major trauma. Due to the difficulty in regeneration of neurons or axons after injury, as well as the inhibition of blood vessel growth by the formation of neural scars, existing treatment measures have limited effectiveness in repairing brain tissue. Herein, the biomultifunctional hydrogels are developed for TBI treatment based on the Schiff base reaction of calcium ion (Ca2+)-cross-linked oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS). The obtained COCS hydrogel exhibits excellent adhesion to wet tissues, self-repair capability, and antimicrobial properties. What's particularly interesting is that the addition of Ca2+ increases the hydrogel's extensibility, enhancing its hemostatic capabilities. Biological assessments indicate that the COCS hydrogel demonstrates excellent biocompatibility, hemostatic properties, and the ability to promote arterial vessel repair. Importantly, the COCS hydrogel promotes the growth of cerebral microvessels by upregulating CD31, accelerates the proliferation of astrocytes, enhances the expression of GFAP, and stimulates the expression of neuron-specific markers such as NEUN and ß-tubulin. All of these findings highlight that the strongly adhesive, self-healing, hemostatic hydrogel shows great potential for the repair of traumatic brain injury and other tissue repair therapy.