ROS-triggered smart hydrogel adhesives for modulating the inflammatory microenvironment and promoting tendon-bone interface regeneration

Currently, suture surgery for rotator cuff repair is unable to regenerate the original functional fibrocartilage layer at the tendon-bone interface, resulting in high postoperative retear rates. In this study, a ROS-triggered smart hydrogel adhesive (DPQP@ME) was designed to synergistically enhance...

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Bibliographic Details
Published in:International Journal of Pharmaceutics: X
Main Authors: Hebei He, Yifen Lin, Jia Fang, Kai He, Wenjun Li, Min Du, Shilong Lin, Xiaofei Zheng, Hanyu Lu
Format: Article
Language:English
Published: Elsevier 2026-06-01
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590156726000228
Description
Summary:Currently, suture surgery for rotator cuff repair is unable to regenerate the original functional fibrocartilage layer at the tendon-bone interface, resulting in high postoperative retear rates. In this study, a ROS-triggered smart hydrogel adhesive (DPQP@ME) was designed to synergistically enhance the functional repair of the tendon-bone interface during suture surgery by modulating the inflammatory microenvironment, promoting cell differentiation, and providing mechanically adaptive support. Metal-phenolic nanoparticles (ME) with multiple bioactivities were formed through the self-assembly of epigallocatechin gallate (EGCG) and Mg2+. Subsequently, ME, dithiothreitol (DTT), polyethylene glycol diacrylate (PEGDA), and boronic acid-modified quaternary ammonium chitosan (QCS-PBA) were crosslinked via borate ester bonds, thioether bonds, and photo-crosslinking to form a bioactive hydrogel adhesive with ROS responsiveness and favorable mechanical properties. Based on the ROS sensitivity of the borate ester bonds and thioether bonds, DPQP@ME exhibited favorable ROS-responsive drug release properties, with ME release reaching 73.15 ± 1.35% in H2O2-containing PBS versus 33.15 ± 1.65% in PBS alone. In vitro cellular experiments demonstrated that DPQP@ME could effectively reduce intracellular ROS levels, regulate macrophage polarization toward an anti-inflammatory phenotype, and promote osteogenic differentiation as well as cartilage formation. Animal studies further demonstrated that DPQP@ME significantly attenuated inflammatory responses and promoted functional reconstruction of the tendon-bone interface. In conclusion, this novel smart hydrogel adhesives provides a promising therapeutic strategy for tendon healing.
ISSN:2590-1567