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-α (TNF-α)). 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-α, 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.

Therapeutic Efficacy of Intratendinous Delivery of Dexamethasone Using Porous Microspheres for Amelioration of Inflammation and Tendon Degeneration on Achilles Tendinitis in Rats

“…In the present study, tenocytes were treated with IL-1β in order to mimic the inflamed condition in vitro. Our previous studies reported that LPS-stimulated tenocytes increase gene expression levels for cytokines (i.e., ADAMTS-5, COX-2, IL-6, TNF-α) as well as ECM-degrading proteinases (i.e., MMP-3 and MMP-13) [1,3]. We found that DEX/PMS systems markedly suppressed the mRNA levels of these cytokines in IL-1β-stimulated tenocytes.…”

“…To produce DEX/PMSs, a simple fluidic device equipped was used as previously described [1,3,13]. First, 140 mg of poly (lactic-co-glycolic acid) (PLGA, 50 : 50, Mw: 30,000-60,000 g/mol, Sigma-Aldrich, St. Louis, MO, USA) was clearly solubilized in dichloromethane (DCM, 7 mL).…”

“…Tendon disorders caused by overuse, aging, or gradual wear and tear are common in athletes and sedentary peoples. Achilles tendinitis involves chronic pain and swelling [1] and induces an inflammatory response. Many inflammatory markers (e.g., tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), matrix metalloproteinases (i.e., MMP-2, -3, -9, and -13, among others), and metabolic enzyme (cyclooxygenase-2, COX-2)) are involved in this process [1][2][3].…”

“…Achilles tendinitis involves chronic pain and swelling [1] and induces an inflammatory response. Many inflammatory markers (e.g., tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), matrix metalloproteinases (i.e., MMP-2, -3, -9, and -13, among others), and metabolic enzyme (cyclooxygenase-2, COX-2)) are involved in this process [1][2][3]. Anti-inflammatory treatment of Achilles tendinitis usually entails noninvasive methods such as treating with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroid treatments, ultrasound, and hot and cold compresses [4].…”

3D printed poly(ε‑caprolactone) scaffolds function with simvastatin‑loaded poly(lactic‑co‑glycolic acid) microspheres to repair load‑bearing segmental bone defects

“…The content of SIM in the microspheres was determined using an ultraviolet (UV) spectrophotometer (Beckman Coulter, Inc., Brea, CA, USA) (26,28–30). UV scanning from 100 to 1,000 nm was used to identify the absorption peak of SIM.…”