Effectiveness of the injectable hyaluronic acid-based microparticles loaded with cannabidiol on rat sciatic nerve injury model.

We have developed an innovative peripheral nerve tissue repair approach by designing biomimetic microparticles loaded with cannabidiol (CBD) using horseradish peroxidase-mediated crosslinking within a microfluidic device. This method utilizes a water-in-oil emulsion system where a mixture of phenol-substituted hyaluronic acid (HAPh), CBD, and laccase is channeled into oil flow, forming hydrogel microparticles. The physical properties, such as their swelling rate, mechanical strength, and the sustained release of CBD, emphasize their potential in tissue engineering and drug delivery applications. Cellular proliferation studies within the microparticles demonstrate their cytocompatibility, making them suitable for developing microtissues. The microparticles also served as a controlled release mechanism for CBD-targeted delivery to the injured locations, showcasing the effectiveness and ability to aid in the regeneration of the sciatic nerve tissue. In vivo, histopathological analysis of treated sciatic nerve injuries showed enhanced axonal restoring and remyelination with HAPh microparticles containing CBD in contrast to control groups. Furthermore, microparticles enhanced various functional aspects of locomotor activities, such as functional sciatic index (SFI) values, response to heat stimulation, and muscle mass retention. In conclusion, results indicate that these composite biomimetic microparticles with CBD effectively promote nerve structural restoration and increase the reconstruction process in a sciatic nerve injury model.