Localized Delivery of miRNAs Targets Cyclooxygenases and Reduces Flexor Tendon Adhesions

Publication date: Available online 7 February 2018
Source:Acta Biomaterialia
Author(s): Youlang Zhou, Qianqian Yang, Yingying Yan, Changlai Zhu, Luzhong Zhang, Jin Bo Tang
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 reducetendonadhesionsby directly targeting the down-regulation of COX-1 and COX-2 expression within the microenvironment of the injured tendon.Statement of SignificanceA 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 attenuatethe formation of tendonadhesionthrough direct downregulation of COX-1 and COX-2 expression within the microenvironment of the injured tendon.

Graphical abstract

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