The use of silver nanoparticles on achilles tendon rupture and their role in the healing process

Abstract

Full recovery from tendon injury remains a challenge in modern medicine. Such injury, for example through wear and tear, lacerations or sports injuries, always entails slow healing, scarring and weakened tissues. Past studies of skin wounds have shown that silver nanoparticles (AgNPs) can accelerate healing, enhance mechanical strength, promote collagen deposition and reduce scarring. It is therefore postulated that AgNPs could improve tendon healing, as skin and tendon are both soft tissues with very similar compositions. However, little is known about the mechanism of AgNPs in promoting healing. This study therefore aimed to describe the effect of AgNPs on tendon healing, specifically for Achilles tendon rupture, and to investigate the possible underlying mechanism(s).

The effect of AgNPs on tendon healing was studied using primary tenocyte culture and a rat Achilles tendon injury model. Cytotoxicity, cell proliferation and differentiation were examined in vitro; tensile properties, collagen and proteoglycan expression were studied in vivo. Alternative treatments including silver ions, gold nanoparticles, non-steroidal anti-inflammatory drugs and glucocorticoids were used for comparison. Similar in vivo study was performed to scrutinize the impact of delayed treatment on tensile modulus. In vivo neutrophil and macrophage infiltration to the wound was observed and in vitro cytokine secretion by adherent peripheral blood mononuclear cells was measured. The results of the in vitro and in vivo study indicated that AgNPs promoted tendon healing. The mechanical properties of the repaired tendon were promoted, which was not observed with the alternative treatments mentioned above. Inflammation was alleviated, cell proliferation and proteoglycan expression were increased and collagen alignment was improved with AgNPs at 6 weeks post injury. The tensile modulus of the tendon showed a decreasing trend with delayed intervention, and treatment started 14 days after injury exhibited no effect on healing. Immunostaining of the tendon showed that AgNPs reduced the influx of neutrophils and macrophages to the wound, and in vitro study of cytokine secretion indicated that AgNPs selectively suppressed the expression of both pro-inflammatory and anti-inflammatory cytokine.

This work demonstrated a promotional effect on tendon healing in the early phase with AgNPs treatment. This effect was unique when compared with drugs with similar physiochemical and biochemical properties. Delayed AgNPs treatment did not show promotion in tensile modulus, suggesting that the immunomodulatory property of AgNPs plays a major role in enhancing healing. The intervention of neutrophil and macrophage infiltration can be a reason for the promotion in healing, as suggested in the literature. The regulatory role of AgNPs on macrophage cytokine secretion suggested a potential mechanism in achieving better healing.

This is the first study to show that AgNPs promote tendon healing and that their action on the inflammatory response is critical. This work on inflammation contributes to the knowledge in the field of nanomedicine and wound healing. Further study will be needed to investigate the principle of AgNPs on cytokine regulation and to confirm the results in an animal model.