Modulating Macrophage Phenotype by Sustained MicroRNA Delivery Improves Host-Implant Integration.
Animals
Blood Vessels
/ growth & development
Female
Foreign-Body Reaction
/ prevention & control
Gene Transfer Techniques
Macrophages
/ pathology
Mice, Inbred C57BL
MicroRNAs
/ administration & dosage
Nanofibers
/ chemistry
Organophosphates
/ chemistry
Polyesters
/ chemistry
Prostheses and Implants
/ adverse effects
RNA interference
electrospinning
fibrous capsule formation
gene silencing
tissue engineering
Journal
Advanced healthcare materials
ISSN: 2192-2659
Titre abrégé: Adv Healthc Mater
Pays: Germany
ID NLM: 101581613
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
06
09
2019
revised:
03
12
2019
pubmed:
20
12
2019
medline:
23
2
2021
entrez:
20
12
2019
Statut:
ppublish
Résumé
Biomedical implant failure due to the host's response remains a challenging problem. In particular, the formation of the fibrous capsule is a common barrier for the normal function of implants. Currently, there is mounting evidence indicating that the polarization state of macrophages plays an important role in effecting the foreign body reaction (FBR). This opens up a potential avenue for improving host-implant integration. Here, electrospun poly(caprolactone-co-ethyl ethylene phosphate) nanofiber scaffolds are utilized to deliver microRNAs (miRs) to induce macrophage polarization and modulate FBR. Specifically, C57BL/6 mice that are treated with M2-inducing miRs, Let-7c and miR-124, display relatively thinner fibrous capsule formation around the scaffolds at both Week 2 and 4, as compared to treatment with M1-inducing miR, Anti-Let-7c. Histological analysis shows that the density of blood vessels in the scaffolds are the highest in miR-124 treatment group, followed by Anti-Let-7c and Let-7c treatment groups. Based on immunohistochemical quantifications, these miR-encapsulated nanofiber scaffolds are useful for localized and sustained delivery of functional miRs and are able to modulate macrophage polarization during the first 2 weeks of implantation to result in significant alteration in host-implant integration at longer time points.
Identifiants
pubmed: 31854130
doi: 10.1002/adhm.201901257
doi:
Substances chimiques
MicroRNAs
0
Mirn124 microRNA, mouse
0
Organophosphates
0
Polyesters
0
mirnlet7 microRNA, mouse
0
poly(caprolactone-co-ethylethylene phosphate)
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1901257Subventions
Organisme : Singapore National Research Foundation
ID : NMRC/CBRG/0096/2015
Pays : International
Organisme : Singapore Ministry of Health's National Medical Research Council
ID : RG148/14
Pays : International
Informations de copyright
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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