Localized delivery of miRNAs targets cyclooxygenases and reduces flexor tendon adhesions

[Display omitted] The formation of adhesions during healing of an injured tendon remains a difficult problem in clinical practice. Local anti-inflammation gene delivery provides high local gene concentration, reduces the inflammatory response of the injured tendon microenvironment, and decreases sys...

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Bibliographic Details
Published in:Acta biomaterialia 2018-04, Vol.70, p.237-248
Main Authors: Zhou, You Lang, Yang, Qian Qian, Yan, Ying Ying, Zhu, Changlai, Zhang, Luzhong, Tang, Jin Bo
Format: Article
Language:English
Subjects:
Animals
Avian Proteins - antagonists & inhibitors
Avian Proteins - metabolism
Chickens
Cyclooxygenase
Cyclooxygenase 1 - metabolism
Cyclooxygenase 2 - metabolism
Cyclooxygenase 2 Inhibitors - pharmacology
Cyclooxygenase-1
Cyclooxygenase-2
Drug Delivery Systems
Embedded systems
Gene expression
Gene transfer
Hyaluronic acid
Hydrogels
In vivo methods and tests
Inflammation
Inflammatory response
Injectable hydrogel
Injury prevention
Localized
MicroRNAs - pharmacology
miRNA
miRNA delivery
Nanoparticles
Reducing flexor tendon adhesions
Ribonucleic acid
RNA
Side effects
Tendon Injuries - drug therapy
Tendon Injuries - enzymology
Tendon Injuries - pathology
Tendons
Tissue Adhesions - enzymology
Tissue Adhesions - pathology
Tissue Adhesions - prevention & control
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Summary:[Display omitted] The formation of adhesions during healing of an injured tendon remains a difficult problem in clinical practice. Local anti-inflammation gene delivery provides high local gene concentration, reduces the inflammatory response of the injured tendon microenvironment, and decreases systemic side effects to enhance in vivo efficacy. In this study, we designed a novel local sustained gene delivery system by using cyclooxygenase (COX-1 and COX-2)-engineered miRNA plasmid/nanoparticles embedded in hyaluronic acid (HA) hydrogel to reduce flexor tendon adhesions. The local sustained gene delivery system significantly downregulates COX-1 and COX-2 expression in the tendon tissue and the surrounding subcutaneous tissue. More importantly, this plasmid/nanoparticle hydrogel system significantly reduced tissue adhesion formation. This approach offers an effective therapeutic strategy to reduce tendon adhesions by directly targeting the down-regulation of COX-1 and COX-2 expression within the microenvironment of the injured tendon. A local sustained gene delivery system was developed to regulate the expression of targeted genes in the specific time and location for tendon adhesion treatment. The engineered miRNA plasmid/nanoparticles embedded in hyaluronic acid hydrogel were synthesized to downregulate the expression of cyclooxygenases in the tendon tissue during the early stage of tendon healing with inflammatory response. This plasmid/nanoparticle hydrogel system offers an effective therapeutic strategy to attenuate the formation of tendon adhesion through direct downregulation of COX-1 and COX-2 expression within the microenvironment of the injured tendon.
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2018.01.047