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

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Mar 26

PMID 35335197

Authors

Junwei He

Xinxian Meng

Chen Meng

Jiayu Zhao

Yunsheng Chen

Zheng Zhang

Yixin Zhang

Affiliations

Soon will be listed here.

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 (CeO) as an enzyme-like ROS scavenger and pirfenidone (PFD) as an anti-fibrotic drug to inhibit the expression of TGF-β. However, CeO 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 in their shell; these NCs were referred to as PFD/CeO NCs. PFD/CeO NCs were supposed to efficiently achieve intracellular delivery of PFD and successfully scavenged ROS from the microenvironment. Cellular experiments verified that PFD/CeO NCs had good biocompatibility, satisfactory cellular uptake, and favorable ROS-scavenging capacity. To be applied directly to the wound, PFD/CeO 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.

Citing Articles

Emerging biomedical technologies for scarless wound healing.

Cao X, Wu X, Zhang Y, Qian X, Sun W, Zhao Y Bioact Mater. 2024; 42:449-477.

PMID: 39308549 PMC: 11415838. DOI: 10.1016/j.bioactmat.2024.09.001.

The regulatory mechanisms of cerium oxide nanoparticles in oxidative stress and emerging applications in refractory wound care.

Yi L, Yu L, Chen S, Huang D, Yang C, Deng H Front Pharmacol. 2024; 15:1439960.

PMID: 39156103 PMC: 11327095. DOI: 10.3389/fphar.2024.1439960.

Endogenous stimuli-responsive separating microneedles to inhibit hypertrophic scar through remodeling the pathological microenvironment.

Yang Z, Suo H, Fan J, Lv N, Du K, Ma T Nat Commun. 2024; 15(1):2038.

PMID: 38448448 PMC: 10917775. DOI: 10.1038/s41467-024-46328-2.

Further Improvement Based on Traditional Nanocapsule Preparation Methods: A Review.

Zhou Y, Wan F, Zhu L, Wang Z, Fan G, Wang P Nanomaterials (Basel). 2023; 13(24).

PMID: 38133022 PMC: 10745493. DOI: 10.3390/nano13243125.

Radioprotective Potency of Nanoceria.

Alvandi M, Shaghaghi Z, Farzipour S, Marzhoseyni Z Curr Radiopharm. 2023; 17(2):138-147.

PMID: 37990425 DOI: 10.2174/0118744710267281231104170435.

References

Hollestein L, Nijsten T . An insight into the global burden of skin diseases. J Invest Dermatol. 2014; 134(6):1499-1501. DOI: 10.1038/jid.2013.513. View

Wells A, Leung K . Pirfenidone attenuates the profibrotic contractile phenotype of differentiated human dermal myofibroblasts. Biochem Biophys Res Commun. 2019; 521(3):646-651. DOI: 10.1016/j.bbrc.2019.10.177. View

Shi K, Wang F, Xia J, Zuo B, Wang Z, Cao X . Pirfenidone inhibits epidural scar fibroblast proliferation and differentiation by regulating TGF-β1-induced Smad-dependent and -independent pathways. Am J Transl Res. 2019; 11(3):1593-1604. PMC: 6456526. View

Carney B, Chen J, Kent R, Rummani M, Alkhalil A, Moffatt L . Reactive Oxygen Species Scavenging Potential Contributes to Hypertrophic Scar Formation. J Surg Res. 2019; 244:312-323. DOI: 10.1016/j.jss.2019.06.006. View

Dorati R, Medina J, DeLuca P, Leung K . Development of a Topical 48-H Release Formulation as an Anti-scarring Treatment for Deep Partial-Thickness Burns. AAPS PharmSciTech. 2018; 19(5):2264-2275. DOI: 10.1208/s12249-018-1030-3. View

Gauglitz G, Korting H, Pavicic T, Ruzicka T, Jeschke M . Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2010; 17(1-2):113-25. PMC: 3022978. DOI: 10.2119/molmed.2009.00153. View

Wu H, Li F, Wang S, Lu J, Li J, Du Y . Ceria nanocrystals decorated mesoporous silica nanoparticle based ROS-scavenging tissue adhesive for highly efficient regenerative wound healing. Biomaterials. 2017; 151:66-77. DOI: 10.1016/j.biomaterials.2017.10.018. View

Gravina N, Maghni K, Welman M, Yahia L, Mbeh D, Messina P . Protective role against hydrogen peroxide and fibroblast stimulation via Ce-doped TiO2 nanostructured materials. Biochim Biophys Acta. 2015; 1860(2):452-64. DOI: 10.1016/j.bbagen.2015.12.001. View

Forbes S, Rosenthal N . Preparing the ground for tissue regeneration: from mechanism to therapy. Nat Med. 2014; 20(8):857-69. DOI: 10.1038/nm.3653. View

10.

Hu M, Rennert R, McArdle A, Chung M, Walmsley G, Longaker M . The Role of Stem Cells During Scarless Skin Wound Healing. Adv Wound Care (New Rochelle). 2014; 3(4):304-314. PMC: 3985511. DOI: 10.1089/wound.2013.0471. View

11.

Cui J, van Koeverden M, Mullner M, Kempe K, Caruso F . Emerging methods for the fabrication of polymer capsules. Adv Colloid Interface Sci. 2013; 207:14-31. DOI: 10.1016/j.cis.2013.10.012. View

12.

Dunnill C, Patton T, Brennan J, Barrett J, Dryden M, Cooke J . Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int Wound J. 2015; 14(1):89-96. PMC: 7950185. DOI: 10.1111/iwj.12557. View

13.

Popov A, Popova N, Tarakina N, Ivanova O, Ermakov A, Ivanov V . Intracellular Delivery of Antioxidant CeO Nanoparticles via Polyelectrolyte Microcapsules. ACS Biomater Sci Eng. 2021; 4(7):2453-2462. DOI: 10.1021/acsbiomaterials.8b00489. View

14.

Popova N, Popov A, Ermakov A, Reukov V, Ivanov V . Ceria-Containing Hybrid Multilayered Microcapsules for Enhanced Cellular Internalisation with High Radioprotection Efficiency. Molecules. 2020; 25(13). PMC: 7411955. DOI: 10.3390/molecules25132957. View

15.

Popov A, Popova N, Gould D, Shcherbakov A, Sukhorukov G, Ivanov V . Ceria Nanoparticles-Decorated Microcapsules as a Smart Drug Delivery/Protective System: Protection of Encapsulated P. pyralis Luciferase. ACS Appl Mater Interfaces. 2018; 10(17):14367-14377. DOI: 10.1021/acsami.7b19658. View

16.

Miguel S, Sequeira R, Moreira A, Cabral C, Mendonca A, Ferreira P . An overview of electrospun membranes loaded with bioactive molecules for improving the wound healing process. Eur J Pharm Biopharm. 2019; 139:1-22. DOI: 10.1016/j.ejpb.2019.03.010. View

17.

Zafar M, Najeeb S, Khurshid Z, Vazirzadeh M, Zohaib S, Najeeb B . Potential of Electrospun Nanofibers for Biomedical and Dental Applications. Materials (Basel). 2017; 9(2). PMC: 5456492. DOI: 10.3390/ma9020073. View

18.

Hall C, Wells A, Leung K . Pirfenidone reduces profibrotic responses in human dermal myofibroblasts, in vitro. Lab Invest. 2018; 98(5):640-655. DOI: 10.1038/s41374-017-0014-3. View

19.

Xin Y, Wang X, Zhu M, Qu M, Bogari M, Lin L . Expansion of CD26 positive fibroblast population promotes keloid progression. Exp Cell Res. 2017; 356(1):104-113. DOI: 10.1016/j.yexcr.2017.04.021. View

20.

Greaves N, Ashcroft K, Baguneid M, Bayat A . Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing. J Dermatol Sci. 2013; 72(3):206-17. DOI: 10.1016/j.jdermsci.2013.07.008. View