Synergistic effect of ROS-generating polydopamine on drug-induced bone tissue regeneration

A PHD (prolyl hydroxylase) inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), is a drug that can artificially promote tissue regeneration by enhancing metabolic activity through the upregulation of hypoxia inducible factor 1 subunit alpha (Hif-1α) under normoxic conditions. This...

Full description

Saved in:
Bibliographic Details
Published in:Nanoscale 2024-11, Vol.16 (43), p.2118-213
Main Authors: Han, Hyeju, Kang, Bongkyun, Sharker, Shazid Md, Kashem, Tabassum Binte, Kim, Yuejin, Lee, Jeehee, Park, Minok, Kim, Eunjeong, Jung, YunJae, Lim, Jinkyu, Ryu, Seungwon, Lee, Kyueui
Format: Article
Language:English
Subjects:
Animals
Bone Regeneration - drug effects
Carboxylic acids
Drug Delivery Systems
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Indoles - chemistry
Indoles - pharmacology
Mice
Polymers - chemistry
Polymers - pharmacology
Prolyl-Hydroxylase Inhibitors - chemistry
Prolyl-Hydroxylase Inhibitors - pharmacology
Reactive Oxygen Species - metabolism
Regeneration (physiology)
Skull - drug effects
Skull - injuries
Skull - metabolism
Skull - pathology
Synergistic effect
Tissue engineering
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A PHD (prolyl hydroxylase) inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), is a drug that can artificially promote tissue regeneration by enhancing metabolic activity through the upregulation of hypoxia inducible factor 1 subunit alpha (Hif-1α) under normoxic conditions. This study presents a novel design methodology for a drug delivery system to maximize the regenerative effect of 1,4-DPCA. Specifically, by encapsulating 1,4-DPCA in polydopamine (PDA) that generates reactive oxygen species (ROS), the combined effects of Hif-1α upregulation and the induction of cellular antioxidant defense mechanisms by localized ROS can significantly enhance tissue regeneration. The study confirmed that each material (PDA and 1,4-DPCA) triggers a positive synergistic effect on the regenerative mechanisms. As a result, the use of a PDA drug delivery system loaded with 1,4-DPCA showed approximately six times greater bone regeneration compared to the control (no treatment) in a mouse calvarial defect model. The combination of PDA NPs and 1,4-DPCA leads to a synergistic effect that enhances bone tissue regeneration in vivo .
ISSN:2040-3364
2040-3372
2040-3372
DOI:10.1039/d4nr02887b