Anti-Adhesive Resorbable Indomethacin/Bupivacaine-Eluting Nanofibers for Tendon Rupture Repair: In Vitro and In Vivo Studies.

The treatment and surgical repair of torn Achilles tendons seldom return the wounded tendon to its original elasticity and stiffness. This study explored the in vitro and in vivo simultaneous release of indomethacin and bupivacaine from electrospun polylactide-polyglycolide composite membranes for their capacity to repair torn Achilles tendons. These membranes were fabricated by mixing polylactide-polyglycolide/indomethacin, polylactide-polyglycolide/collagen, and polylactide-polyglycolide/bupivacaine with 1,1,1,3,3,3-hexafluoro-2-propanol into sandwich-structured composites. Subsequently, the in vitro pharmaceutic release rates over 30 days were determined, and the in vivo release behavior and effectiveness of the loaded drugs were assessed using an animal surgical model. High concentrations of indomethacin and bupivacaine were released for over four weeks. The released pharmaceutics resulted in complete recovery of rat tendons, and the nanofibrous composite membranes exhibited exceptional mechanical strength. Additionally, the anti-adhesion capacity of the developed membrane was confirmed. Using the electrospinning technique developed in this study, we plan on manufacturing degradable composite membranes for tendon healing, which can deliver sustained pharmaceutical release and provide a collagenous habitat.

Tri-Layered Doxycycline-, Collagen- and Bupivacaine-Loaded Poly(lactic-co-glycolic acid) Nanofibrous Scaffolds for Tendon Rupture Repair.

Achilles tendon rupture is a severe injury, and its optimal therapy remains controversial. Tissue engineering scaffolds play a significant role in tendon healing and tissue regeneration. In this study, we developed tri-layered doxycycline/collagen/bupivacaine (DCB)-composite nanofibrous scaffolds to repair injured Achilles tendons. Doxycycline, collagen, and bupivacaine were integrated into poly(lactic-co-glycolic acid) (PLGA) nanofibrous membranes, layer by layer, using an electrospinning technique as healing promoters, a 3D scaffold, and painkillers, respectively. After spinning, the properties of the nanofibrous scaffolds were characterized. In vitro drug discharge behavior was also evaluated. Furthermore, the effectiveness of the DCB-PLGA-composite nanofibers in repairing ruptured Achilles tendons was investigated in an animal tendon model with histological analyses. The experimental results show that, compared to the pristine PLGA nanofibers, the biomolecule-loaded nanofibers exhibited smaller fiber size distribution and an enhanced hydrophilicity. The DCB-composite nanofibers provided a sustained release of doxycycline and bupivacaine for over 28 days in vivo. Additionally, Achilles tendons repaired using DCB-composite nanofibers exhibited a significantly higher maximum load-to-failure than normal tendons, suggesting that the biomolecule-incorporated nanofibers are promising scaffolds for repairing Achilles tendons.