Inhibition of ROS activity by controlled release of proanthocyanidins from mesoporous silica nanocomposites effectively ameliorates heterotopic ossification in tendon

• High levels of reactive oxygen species (ROS) were found in tendinopathy. • MSNs-PC promote tenogenesis differentiation of TSPCs. • MSNs-PC alleviated heterotopic tendon ossification by scavenging excess ROS. In the inflammatory environment of tendinopathy, tendon stem/progenitor cells (TSPCs) have been demonstrated to aberrantly differentiate into osteochondral lineage causing late-stage heterotopic ossification (HO) of the tendon, which severely damages tissue function and worsens patients’ activities. However, no effective treatment for tendinopathy currently exist because the mechanism underlying the TSPCs abnormal differentiation is unclear. In this article, high levels of reactive oxygen species (ROS) were found in tendinopathy samples. In vitro results revealed that proanthocyanidins (PC) can potentially regulate the differentiation of TSPCs by scavenging excess ROS, which would promote tenogenesis instead of chondrogenesis or osteogenesis. Moreover, in vivo results demonstrated that PC-loaded mesoporous silica nanocomposite (MSNs-PC) hinders the recurrence of HO in repaired tendons owing to the inhibition of oxidative stress, showing anti-inflammatory effects. Our findings indicate a high level of ROS in tendinopathy, which is probably the cause of aberrant differentiation of TSPCs. MSNs-PCs can effectively ameliorate HO of the tendon by scavenging excess ROS, providing a promising avenue to for other ROS-related diseases.