Simultaneous effects of hydrostatic pressure and dexamethasone release from electrospun fibers on inflammation-induced chondrocytes

Osteoarthritis (OA) is one of the major causes of disability worldwide. The characteristics of OA are increasing cell death, production of inflammatory cytokines, and changes in the function of the cell nucleus in the synthesis of destructive enzymes. Tissue engineering is a promising and ongoing process to suppress inflammation and rebuild the lost tissue. The aim of this research study is to investigate the simultaneous effect of hydrostatic pressure and dexamethasone (DEX) on immortalized human chondrocytes cell lines (C28/12). To achieve this, first, dexamethasone (DEX) loaded electrospun poly(lactic acid) (PLA) fibers were prepared via electrospinning. Then, the release profile of DEX was evaluated under hydrostatic pressure (HP) with different magnitudes and frequencies. Based on the release profile of DEX from electrospun fibers and the physiological hydrostatic pressure of the cartilage, one of the applied regimes has been selected. Afterwards, C28/I2 was cultured on electrospun poly(lactic acid) (PLA) and DEX loaded PLA electrospun fiber and was grown in static and HP situation. After 7 days of exposure phorbol-12-myristate-13-acetate (PMA) to cultured cells on DEX loaded PLA scaffolds under hydrostatic pressure condition, cell viability and collagen deposition increased 3.63 and 1.85 times and nitric oxide production decreased 0.242 times in comparison to cultured PMA-stimulated cells on DEX loaded PLA. Moreover, through real time-PCR analysis, it was demonstrated that pairing HP and DEX led to reduced inducible nitric-oxide synthase (iNOS) and matrix metalloproteinase-13 (MMP-13) expressions by 0.01 and 0.041 times in comparison to static groups. However, expression of collagen type II did not enhance in the coupled system of HP and DEX. In conclusion, the presence of HP increased the DEX release from the nanofibrous scaffold and improved its ability as a drug depot scaffold for outstanding reduction of inflammation factors.