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

Hong Joon Choi, Somang Choi, Jae Gyoon Kim, Mi Hyun Song, Kyu Sik Shim, Youn Mook Lim, Hak Jun Kim, Kyeongsoon Park, Sung Eun Kim

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

    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.

    Original languageEnglish
    Article number116284
    JournalCarbohydrate Polymers
    Volume241
    DOIs
    Publication statusPublished - 2020 Aug 1

    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

    ASJC Scopus subject areas

    • Organic Chemistry
    • Polymers and Plastics
    • Materials Chemistry

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