Nanofibrous polycaprolactone/amniotic membrane facilitates peripheral nerve regeneration by promoting macrophage polarization and regulating inflammatory microenvironment.

Appropriate levels of inflammation are an important part of functional repair of nerve damage. However, excessive inflammation can cause the continuous activation of immune inflammatory cells and degeneration of nerve cells. Regulating the temporal and spatial changes in M1/M2 macrophages can regulate the local inflammatory immune environment of the tissue to promote its transformation to a direction conducive to tissue repair.In the present study, a multi-layer multifunctional nanofiber composite membrane of polycaprolactone(PCL) and amniotic membrane (AM) was constructed using electrospinning. In vitro studies have shown that the PCL/AM composite promoted the axon growth of SH-SY5Y cells and induced their differentiation into neurons. The PCL/AM composite wrapped the nerve stump to form a microenvironment that was conducive to nerve regeneration, blocked the invasion of scar tissue, promoted the recruitment of macrophages and moderate polarization to M2, enhanced the expression of anti-inflammatory factors IL-10 and IL-13, inhibited the expression of pro-inflammatory factors IL-6 and TNF-α, and induced myelin sheath and axon regeneration. By releasing various bioactive substances to regulate the polarization of M2 macrophages and formation of anti-inflammatory factors, the PCL/AM composite can enhance axonal regeneration and improve nerve repair.

Multilayer amnion-PCL nanofibrous membrane loaded with celecoxib exerts a therapeutic effect against tendon adhesion by improving the inflammatory microenvironment.

Tendon adhesion is a common complication after tendon surgery. The inflammatory phase of tendon healing is characterized by the release of a large number of inflammatory factors, whose mediated excessive inflammatory response is an important cause of tendon adhesion formation. Nonsteroidal anti-inflammatory drugs(NSAIDs) were used to prevent tendon adhesions by reducing the inflammatory response. However, recent studies have shown that the NSAIDs partially impairs tendon healing. Therefore, optimizing the anti-adhesive membrane loaded with NSAIDs to mitigate the effects on tendon healing requires further in-depth study. Amniotic membranes(AM) are natural polymeric semi-permeable membranes from living organisms that are rich in matrix, growth factors, and other active ingredients. In this study, we used electrostatic spinning technology to construct multifunctional nanofiber membranes of the PCL membrane loaded with celecoxib and AM. In vitro cellular assays revealed that celecoxib-loaded PCL membranes significantly inhibited the adhesion and proliferation of fibroblasts with increasing concentrations of celecoxib. In a rabbit tendon repair model, biomechanical tests further confirmed that the PCL membrane loaded with celecoxib had better anti-adhesion effects. Further experimental studies revealed that the PCL/AM membrane improved the inflammatory microenvironment by downregulating the expression of pro-inflammatory factors such as COX-2, IL-1ß, and TNF-α proteins; and inhibiting the synthesis of COL I and COL Ⅲ. The PCL/AM membrane can continuously release celecoxib to reduce the inflammatory response and deliver growth factors to the damaged area to build a suitable microenvironment for tendon repair, which provides a new direction to improve the repair efficiency of tendon.