Abstract
An increase in the levels of reactive oxygen species (ROS) and high expression levels of transforming growth factor-β (TGF-β) in wound tissue are two major problems for wound repair and scar inhibition. Modulation of the wound microenvironment is considered to be able to overcome these issues. Two possible solutions include the use of cerium oxide nanoparticles (CeO2) as an enzyme-like ROS scavenger and pirfenidone (PFD) as an anti-fibrotic drug to inhibit the expression of TGF-β. However, CeO2 is easily adsorbed by biological macromolecules and loses its enzyme-like activity. Furthermore, the intracellular delivery of PFD is difficult. Herein, the layer-by-layer method was used to prepare nanocapsules (NCs) with a sophisticated structure featuring PFD at their core and CeO2 in their shell; these NCs were referred to as PFD/CeO2 NCs. PFD/CeO2 NCs were supposed to efficiently achieve intracellular delivery of PFD and successfully scavenged ROS from the microenvironment. Cellular experiments verified that PFD/CeO2 NCs had good biocompatibility, satisfactory cellular uptake, and favorable ROS-scavenging capacity. To be applied directly to the wound, PFD/CeO2 NCs were then adhered to plasma-etched polylactic acid (PLA) fiber membranes to prepare a new wound dressing. Animal experiments further demonstrated that the dressing accelerated the epithelialization of the wound, reduced the levels of ROS and TGF-β, improved the arrangement and proportion of collagen fibers, and finally, achieved satisfactory wound-repairing and anti-scarring effects. These results provide a new concept for promoting wound repair and preventing scar formation.
Highlights
Human skin is limited by its own ability to repair itself following injuries that penetrate beyond the epidermis
polylactic acid (PLA)-fiber membranes loaded with PFD/CeO2 NCs are an ideal wound dressing for promoting wound repair and preventing scar formation
After 30 min, Normal human fibroblasts (NHF) were washed with PBS, images were taken with a fluorescence microscope, and analysis was performed with Image-Pro Plus 6.0
Summary
Human skin is limited by its own ability to repair itself following injuries that penetrate beyond the epidermis. Polyelectrolyte nanocapsules (NCs) have been regarded as feasible carriers for the delivery of various drugs, and metallic oxide nanoparticles (such as TiO2, SiO2 and Fe3O4) can be introduced into these NCs by applying the layer-by-layer (LbL) method [14] In this form, CeO2 is usually stabilized by citric acid and is negatively charged in a water system. In the form of NCs shell, CeO2 can maintain ROS-scavenging capacity both extracellularly and intracellularly, and provide a highly efficient option for promoting wound repair [16]. PLA-fiber membranes loaded with PFD/CeO2 NCs are an ideal wound dressing for promoting wound repair and preventing scar formation. The PFD/CeO2-NC-loaded PLA dressing displayed the therapeutic functions of CeO2 and PFD, and avoided the defects of their direct application Those findings provide new Molecules 2022, 27, x FOR PEER REVinIEsWight into the design of composite functional wound dressings for prom4otoifn1g6 wound repair and preventing scar formation (Scheme 1). To investigate the effects of the two main components, PFD and CeO2, in subsequent experiments, PFD NCs and CeO2 NCs were prepared by replacing PFD solution with water during synthesis or replacing CeO2 with DS as the fourth layer, respectively
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