Effect of methylprednisolone loaded poly lactic-co-glycolic acid (PLGA) bioabsorbable nanofibers on tendon healing and adhesion formation

Background: Nanomaterials have been widely used in many fields such as vaccination and drug delivery. Beside its behavior as a degradable physical barrier, it can provide a controlled drug release. Tendon healing is a process full of complications, one of which is adhesion caused by excessive fibrosis. Aim: In this study, we aimed to prevent adhesion formation by using methylprednisolone (MP) loaded Poly lactic-co-glycolic acid (PLGA) mats. We used PLGA mats as both, biodegradable physical barrier to reduce the contact between surrounding tissues and healing tendon and as a drug delivery vehicle to release the antifibrotic MP with a controlled pattern. Methods: MP-loaded PLGA nanofiber mats were produced using electrospinning technique under optimized parameters. To find the optimal MP dose, the drug was loaded in 15%, 25% and 35% concentrations. In vitro analysis included FT-IR, antibacterial, water absorption, biodegradability and drug release behavior tests. 70 rats' tendons were used for this study. After scarification of the rats, tendons were analyzed in terms of macroscopic, histopathological and biomechanical evaluation. Results: The neat PLGA and 15%, 25%, and 35% MP-loaded nanofibers lost 47%, 83%, 88%, and 97% of their initial weights at the end of the 8 weeks' degradation process. Within the first 24 h, mats including higher drug concentrations showed more initial release burst effect than samples loaded with lower concentrations. Cumulative drug release at 24 h was 29.5%, 27.6%, and 24.7% for PLGA nanofiber samples containing 15%, 25%, 35% MP, respectively. Macroscopically, When the groups were compared, no statistically significant difference was found between group 1 (no surgical intervention) and group 5 (25% MP/PLGA) in terms of length, characteristics and degree of the adhesion. Comparing to other groups statistically significant atrophic effect was found in group 6 (35% MP/PLGA). Conclusion: 25% MP-loaded PLGA reduces the formation of adhesions macroscopically comparable to tendons that didn't receive any surgical intervention. Microscopically, it provides better tendon healing compared to tendons that received only surgical repair or surgery + neat PLGA. Methylprednisolone did not only add an antibacterial effect to PLGA but also increased the hydrophilic property and degradation rate of PLGA. Increased steroid concentration also leads to atrophy at the healing tendons which can be prevented by modifying the PLGA design