Dual functional core-sheath electrospun hyaluronic acid/polycaprolactone nanofibrous membranes embedded with silver nanoparticles for prevention of peritendinous adhesion

Peritendinous adhesions, one of the common complications after tendon injury and subsequent surgery, could be minimized by directly placing a physical barrier between the injured site and the surrounding tissue. We used silver (Ag) nanoparticles embedded in electrospun hyaluronic acid (HA)/polycaprolactone (PCL) nanofibrous membranes (NFMs) (HA/PCL + Ag NFMs) to prevent peritendinous adhesions and bacterial infection after tendon surgery. HA was used for effective lubrication, and Ag provided antibacterial activity. A dual functional anti-adhesion barrier with core-sheath nanofibrous architecture was made from an HA core solution and a photo-reduced silver nitrate/PCL sheath solution. Polycaprolactone NFMs (PCL NFMs), hyaluronic acid/polycaprolactone core-sheath NFMs (HA/PCL NFMs) and HA/PCL + Ag NFMs with comparable fiber diameters and pore sizes were prepared and analyzed. The microporous structure of NFMs is expected to effectively block the penetration of adhesion-forming fibroblasts during tendon healing. The release of Ag from HA/PCL + Ag NFMs plateaued after 4 days, which confirmed the short-term anti-bacterial effect, and this result was verified with agar diffusion tests. In contrast, the release of HA was extended up to 21 days to simulate the lubrication effect offered by HA in the synovial fluid of the tendon sheath. In vitro cell culture experiments revealed that HA/PCL + Ag NFMs exhibited the highest inhibition of fibroblast attachment and proliferation without significant cytotoxicity due to the synergistic effect of Ag and HA. In vivo studies with a rabbit flexor tendon model further confirmed the efficacy of HA/PCL + Ag NFMs in reducing peritendinous adhesion as determined by gross observation, histology, joint range-of-motion, tendon gliding and biomechanical tests.