Investigation of the effect of exosome added on polycaprolactone scaffold on cartilage regeneration in rabbit septum cartilage defects: An experimental study

Nasal septum perforation (NSP) is defined as a composite tissue loss affecting the mucosa, bone and cartilage tissues of the nasal septum. It affects 0.9% of the general population. Nasal septum perforations are an important cause of morbidity due to their clinical presentation and the functional loss caused by the damage seriously reduces the quality of life of the patients. Although surgical treatment options and many interpositional graft materials have been tried together, none of these treatments give satisfactory results and regenerative medicine applications attract attention in the search for alternative treatment in this field. The aim of this study was to investigate the therapeutic efficacy of the combination of biocompatible, absorbable, low immunogenicity PKL tissue scaffold designed in 3D printer and exosomes obtained from WJ-MKH on septum perforations. In the study, 24 male New Zealand rabbits aged 6-9 months were used. Subjects were divided into 4 groups. In all groups, the nasal septum was surgically accessed and a 7x7 mm perforation was created. The 1st group (control) was followed without treatment, the 2nd group was treated with exosome treatment in GelMA scaffold of the same size as the defect. The 3rd group received only tissue scaffold. The 4th group (combined) was treated by implanting exosomes in the tissue scaffold. After 12 weeks of follow-up, septum samples were obtained. Histopathology, immunohistochemical analysis and SEM imaging were performed on the obtained septum samples. The highest amount of perforation closure was observed in group 4. Although a similar number of complete closure was observed in group 2 and group 3, no improvement in perforation was observed in the control group. In histopathological evaluation, although high scores were obtained in all experimental groups compared to the control group, the highest scores were observed in the combined group. There was a statistical difference in the evaluation of cellular proliferation compared to the control group and a statistical difference was evaluated in group 4 and group 3 compared to the other two groups in the evaluation of type 2 collagen expression applied exosome. SEM analysis showed that the surface morphology of the newly formed tissues was compatible with the natural cartilage tissue and cellular implantations were detected in the porous structure of the scaffold. Traditional surgical and autologous graft methods in the treatment of nasal septal perforations do not yield adequate results due to limited success rates and various complications (graft rejection, infection, inadequate repair, etc.). This situation has brought regenerative medicine applications to the forefront. In the present study, PKL and HA-based hybrid scaffold attracted attention with its biocompatible structure and properties supporting cartilage regeneration; it was observed to increase vascularisation, regulate inflammatory response and promote chondrocyte proliferation. In addition, it was determined that the expression of Type II collagen, which plays a critical role in tissue healing, increased with this system. In addition, WJ-MKH-derived exosomes, which are considered to be a safer alternative to stem cell therapies, were found to synergistically support perforation healing when used in combination with tissue scaffold. GelMA hydrogel was used as a carrier for the effective release of exosomes into the target tissue and significant improvement in histological parameters was obtained with this combination. In conclusion, this study demonstrated that this cell-free and biocompatible regenerative approach may be an effective and low complication alternative for the treatment of nasal septal perforations.