Promotion of collagen deposition during skin healing through Smad3/mTOR pathway by parathyroid hormone-loaded microneedle

Abstract

Skin wounds are associated with huge economic and emotional burdens for millions of people annually and are a challenge for health workers worldwide. At present, for skin defects after traumatic accidents, especially large-area skin defects, newly developed strategies such as the use of emerging biomaterials and cell therapy could be considered as options besides classic skin grafts. However, the new strategies have to deal with problems such as immune rejection and high costs for patients. An insufficient understanding of the mechanisms of skin wound healing further hinders the development of innovative treatment approaches. In this study, we developed a parathyroid hormone (PTH)-loaded phase-transition microneedle (PTMN) patch to deliver PTH subcutaneously in an efficient manner and change microneedle patch daily to achieve intermittent and systematic drug administration. By evaluating wound closure, re-epithelialization, collagen deposition, and extracellular matrix (ECM) expression in a Sprague-Dawley rat model of traumatic skin wounds, we demonstrated that intermittent systemic administration of PTH using our PTMN patches accelerated skin wound healing. Further, we demonstrated that the use of the patch may accelerate skin wound healing depending on the activation of the transforming growth factor (TGF)-β/Smad3/mammalian target of rapamycin (mTOR) cascade pathway. Our results suggest that the PTH-loaded PTMN patch may be a novel therapeutic strategy for treating skin wounds.

Keywords: Microneedle; Parathyroid hormone; Skin healing; Skin wound; TGF-β1; mTOR.