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

Abstract

Injured spinal cords have a limited ability to regenerate because of the inhibitory environment formed in situ that affects neuronal regrow. Ensuring stable contact between the injuried 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-glycerophosphate 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 summary, we propose a material that is compatible with different therapies for soft tissue healing, including repairing injured nerve tissue.