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

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 expressions of pro-inflammatory cytokines (Matrix metalloproteinase-3 (), cyclooxygenase-2 (), interleukin-6 (), and tumor necrosis factor-α ()). In addition, the local injection of SIM/PMSs into the tendons of collagenase-induced Achilles tendinitis rat models suppressed pro-inflammatory cytokines (, , , , and ). This local treatment also upregulated anti-inflammatory cytokines (, , and ). 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.