Development and in vitro assessment of injectable, adhesive, and self-healing chitosan-based hydrogels for treatment of spinal cord injury

Injured spinal cords have a limited ability to regenerate because of the inhibitory environment formed in situ that impacts neuronal regrow. The application of chitosan hydrogels crosslinked with β-glycerophosphate (β-GP) has shown promise in tissue engineering applications; however, ensuring stable contact between the injury nerves to support neural regeneration in the lesion microenvironment remains a significant challenge. To address this challenge, we have engineered a new injectable and adhesive hydrogel to treat spinal cord injuries. This hydrogel was produced by functionalizing chitosan with catechol groups and crosslinking it with different amounts of β-GP to obtain adhesive hydrogels with tunable mechanical properties. The softest hydrogel (G' ~ 300 Pa) demonstrated strong adhesion to different biological soft tissues, including porcine skin (adhesion strength of 3.4 ± 0.9 kPa) and spinal cord, as well as injectability and self-healing abilities, making it ideal for a minimally invasive administration in difficult-to-reach areas. Additionally, this composition promoted the attachment, viability, proliferation and the expression of neuronal marker β-III tubulin (Tuj-1) by the neuroblastoma SH-SY5Y cells. Moreover, SH-SY5Y cells cultured on the hydrogel modulated its mechanical properties (G' ~ 3500 Pa). In a summary, we propose a strategy that is compatible with different therapies for soft tissue healing, including repairing injured nerve tissue.