No abstract

The hierarchical architecture and complex biologic functions of native sheath make its biomimetic substitute a daunting challenge. In this study, a biomimetic bilayer sheath membrane consisting of hyaluronic acid-loaded poly(ε-caprolactone) (HA/PCL) fibrous membrane as the inner layer and PCL fibrous membrane as the outer layer was fabricated by a combination of sequential and microgel electrospinning technologies. This material was characterized by mechanical testing and analysis of morphology, surface wettability, and drug release. Results of an in vitro drug release study showed sustained release. The outer layer had fewer cells proliferating on its surface compared to tissue culture plates or the inner layer. In a chicken model, peritendinous adhesions were reduced and tendon gliding were improved by the application of this sheath membrane. Taken together, our results demonstrate that such a biomimetic bilayer sheath can release HA sustainably as well as promoting tendon gliding and preventing adhesion.

Peritendinous tissue fibrosis which leads to poor tendon function is a worldwide clinical problem; however, its mechanism remains unclear. Transcription factor RelA/p65, an important subunit in the NF-κB complex, is known to have a critical role in many fibrotic diseases. Here, we show that RelA/p65 functions as a core fibrogenic regulator in tendon adhesion and that its inhibition exerts an anti-fibrogenic effect on peritendinous adhesion. We detected the upregulation of the NF-κB pathway in human tendon adhesion using a gene chip microarray assay and revealed the overexpression of p65 and extracellular matrix (ECM) proteins Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) in human fibrotic tissues by immunohistochemistry and western blotting. We also found that in a rat model of tendon injury, p65 expression correlated with tendon adhesion, whereas its inhibition by small interfering (si)RNA prevented fibrous tissue formation and inflammatory reaction as evidenced by macroscopic, biomechanical, histological, immunohistochemical, and western blotting analyses. Furthermore, in cultured fibroblasts, p65-siRNA, p65-specific inhibitor, Helenalin and JSH23 suppressed cell proliferation and promoted apoptosis, whereas inhibiting the mRNA and protein expression of ECM components and cyclo-oxygenase-2, an inflammatory factor involved in tendon adhesion. Our findings indicate that p65 has a critical role in peritendinous tissue fibrosis and suggest that p65 knockdown may be a promising therapeutic approach to prevent tendon adhesion.