Layer-by-Layer Pirfenidone/Cerium Oxide Nanocapsule Dressing Promotes Wound Repair and Prevents Scar Formation

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 p...

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Main Authors: Junwei He, Xinxian Meng, Chen Meng, Jiayu Zhao, Yunsheng Chen, Zheng Zhang, Yixin Zhang
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/6/1830
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author Junwei He
Xinxian Meng
Chen Meng
Jiayu Zhao
Yunsheng Chen
Zheng Zhang
Yixin Zhang
author_facet Junwei He
Xinxian Meng
Chen Meng
Jiayu Zhao
Yunsheng Chen
Zheng Zhang
Yixin Zhang
author_sort Junwei He
collection DOAJ
description 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 (CeO<sub>2</sub>) as an enzyme-like ROS scavenger and pirfenidone (PFD) as an anti-fibrotic drug to inhibit the expression of TGF-β. However, CeO<sub>2</sub> 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 CeO<sub>2</sub> in their shell; these NCs were referred to as PFD/CeO<sub>2</sub> NCs. PFD/CeO<sub>2</sub> NCs were supposed to efficiently achieve intracellular delivery of PFD and successfully scavenged ROS from the microenvironment. Cellular experiments verified that PFD/CeO<sub>2</sub> NCs had good biocompatibility, satisfactory cellular uptake, and favorable ROS-scavenging capacity. To be applied directly to the wound, PFD/CeO<sub>2</sub> 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.
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spelling doaj.art-2c5e7b6735474d479be855d506133cea2023-11-30T21:41:51ZengMDPI AGMolecules1420-30492022-03-01276183010.3390/molecules27061830Layer-by-Layer Pirfenidone/Cerium Oxide Nanocapsule Dressing Promotes Wound Repair and Prevents Scar FormationJunwei He0Xinxian Meng1Chen Meng2Jiayu Zhao3Yunsheng Chen4Zheng Zhang5Yixin Zhang6Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Rd., Shanghai 200011, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Rd., Shanghai 200011, ChinaCollege of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, ChinaCollege of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Rd., Shanghai 200011, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Rd., Shanghai 200011, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Rd., Shanghai 200011, ChinaAn 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 (CeO<sub>2</sub>) as an enzyme-like ROS scavenger and pirfenidone (PFD) as an anti-fibrotic drug to inhibit the expression of TGF-β. However, CeO<sub>2</sub> 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 CeO<sub>2</sub> in their shell; these NCs were referred to as PFD/CeO<sub>2</sub> NCs. PFD/CeO<sub>2</sub> NCs were supposed to efficiently achieve intracellular delivery of PFD and successfully scavenged ROS from the microenvironment. Cellular experiments verified that PFD/CeO<sub>2</sub> NCs had good biocompatibility, satisfactory cellular uptake, and favorable ROS-scavenging capacity. To be applied directly to the wound, PFD/CeO<sub>2</sub> 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.https://www.mdpi.com/1420-3049/27/6/1830wound repairscar preventioncerium oxide nanoparticlespirfenidonenanocapsulesdressing
spellingShingle Junwei He
Xinxian Meng
Chen Meng
Jiayu Zhao
Yunsheng Chen
Zheng Zhang
Yixin Zhang
Layer-by-Layer Pirfenidone/Cerium Oxide Nanocapsule Dressing Promotes Wound Repair and Prevents Scar Formation
Molecules
wound repair
scar prevention
cerium oxide nanoparticles
pirfenidone
nanocapsules
dressing
title Layer-by-Layer Pirfenidone/Cerium Oxide Nanocapsule Dressing Promotes Wound Repair and Prevents Scar Formation
title_full Layer-by-Layer Pirfenidone/Cerium Oxide Nanocapsule Dressing Promotes Wound Repair and Prevents Scar Formation
title_fullStr Layer-by-Layer Pirfenidone/Cerium Oxide Nanocapsule Dressing Promotes Wound Repair and Prevents Scar Formation
title_full_unstemmed Layer-by-Layer Pirfenidone/Cerium Oxide Nanocapsule Dressing Promotes Wound Repair and Prevents Scar Formation
title_short Layer-by-Layer Pirfenidone/Cerium Oxide Nanocapsule Dressing Promotes Wound Repair and Prevents Scar Formation
title_sort layer by layer pirfenidone cerium oxide nanocapsule dressing promotes wound repair and prevents scar formation
topic wound repair
scar prevention
cerium oxide nanoparticles
pirfenidone
nanocapsules
dressing
url https://www.mdpi.com/1420-3049/27/6/1830
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AT chenmeng layerbylayerpirfenidoneceriumoxidenanocapsuledressingpromoteswoundrepairandpreventsscarformation
AT jiayuzhao layerbylayerpirfenidoneceriumoxidenanocapsuledressingpromoteswoundrepairandpreventsscarformation
AT yunshengchen layerbylayerpirfenidoneceriumoxidenanocapsuledressingpromoteswoundrepairandpreventsscarformation
AT zhengzhang layerbylayerpirfenidoneceriumoxidenanocapsuledressingpromoteswoundrepairandpreventsscarformation
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