Enhanced tendon restoration effects of anti-inflammatory, lactoferrin-immobilized, heparin-polymeric nanoparticles in an Achilles tendinitis rat model

Abstract

Gradual wear and tear can cause a local inflammatory response in tendons. The trauma and inflammatory reaction eventually impair the biomechanical properties of the tendon. In this study, we prepared lactoferrin-immobilized, heparin-anchored, poly(lactic-co-glycolic acid) nanoparticles (LF/Hep-PLGA NPs) and evaluated their in vitro anti-inflammatory effects on interleukin-1β (IL-1β)-treated tenocytes and in vivo tendon healing effects in a rat model of Achilles tendinitis. Long-term LF-deliverable NPs (LF/Hep-PLGA NPs) remarkably decreased mRNA levels of pro-inflammatory factors [cyclooxygenase-2 (COX-2), IL-1β, matrix metalloproteinase-3 (MMP-3), MMP-13, IL-6, and tumor necrosis factor-α (TNF-α)] and increased mRNA levels of anti-inflammatory cytokines (IL-4 and IL-10) in both IL-1β-treated tenocytes and the Achilles tendons of a collagenase-induced Achilles tendinitis rat model. Interestingly, anti-inflammatory LF/Hep-PLGA NPs greatly enhanced collagen content, mRNA levels of tenogenic markers [collagen type I (COL1A1), decorin (DCN), tenascin-C (TNC)], and biomechanical properties such as tendon stiffness and tensile strength. These results suggest that anti-inflammatory LF/Hep-PLGA NPs are effective at restoring tendons in Achilles tendinitis.

Keywords: 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (PubChem CID: 2723939); 2-(N-morpholino)-ethanesulfonic acid (PubChem CID:4478249); Dichloromethane (DCM) (PubChem CID: 6344); Dopamine hydrochloride (PubChem CID:65340); Heparin sodium (PubChem CID: 22833565); Lactoferrin (PubChem CID: 126456119, Mw: 3128.8 g/mol); N-hydroxysuccinimide (NHS) (PubChem CID: 80170); Poly (lactic-co-glycolic acid) (PLGA) (PubChem CID: 23111554); Polyvinyl Alcohol (PVA) (PubChem CID: 11199); Sodium Chloride (PubChem CID:5234); inflammatory factors; nanoparticles; sustained lactoferrin delivery; tendon healing; tenocytes.