Parathyroid Hormone-Loaded Microneedle Promotes Tendon Healing Through Activation of mTOR

Tendon rupture/defects may impose a huge economic and mental burden on patients and society. At present, neither surgery nor conservative treatment regimens can provide long-term therapeutic benefits, and the prognosis is often disappointing owing to the loss of tendon function and strength. There is an urgent need for innovative strategies to treat defective tendons. Here, a microneedle patch is developed for the efficient transdermal delivery of parathyroid hormone (PTH). The microneedle tip is made up of polyvinyl alcohol (PVA) and is water swellable, but insoluble, thereby ensuring the accurate and efficient release of PTH, while evacuating the skin without any tip material deposition. The PTH-loaded microneedle patch is replaced daily in a rat tendon defect-healing model. Results from histology, biomechanics, and gene expression analysis confirm that this newly developed microneedle patch accelerates tendon healing following the subcutaneous delivery of PTH and activates the transforming growth factor (TGF)-beta 1/mothers against decapentaplegic homolog 3 (Smad3)/mammalian target of rapamycin (mTOR) signaling cascade, which may be involved in the underlying mechanism. These results suggest that the PTH-loaded microneedle patch developed herein may serve as a novel therapeutic strategy for the treatment of injured tendons.