Exploring the In Vivo Anti-Inflammatory Actions of Simvastatin-Loaded Porous Microspheres on Inflamed Tenocytes in a Collagenase-Induced Animal Model of Achilles Tendinitis

Abstract

Tendon rupture induces an inflammatory response characterized by release of pro-inflammatory cytokines and impaired tendon performance. This study sought to investigate the therapeutic effects of simvastatin-loaded porous microspheres (SIM/PMSs) on inflamed tenocytes in vitro and collagenase-induced Achilles tendinitis in vivo. The treatment of SIM/PMSs in lipopolysaccharide (LPS)-treated tenocytes reduced the mRNA expressions of pro-inflammatory cytokines (Matrix metalloproteinase-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)). In addition, the local injection of SIM/PMSs into the tendons of collagenase-induced Achilles tendinitis rat models suppressed pro-inflammatory cytokines (MMP-3, COX-2, IL-6, TNF-alpha, and MMP-13). This local treatment also upregulated anti-inflammatory cytokines (IL-4, IL-10, and IL-13). Furthermore, treatment with SIM/PMSs also improved the alignment of collagen fibrils and effectively prevented collagen disruption in a dose-dependent manner. Therefore, SIM/PMSs treatment resulted in an incremental increase in the collagen content, stiffness, and tensile strength in tendons. This study suggests that SIM/PMSs have great potential for tendon healing and restoration in Achilles tendinitis.