# Organic di-selenide hydrogel microspheres for multimodal treatment of osteoarthritis

## TL;DR

A new hydrogel microsphere treatment for osteoarthritis targets multiple tissues and processes to reduce joint damage and improve function.

## Contribution

A dual-responsive hydrogel microsphere is developed to modulate selenoprotein levels across multiple tissues for multimodal osteoarthritis treatment.

## Key findings

- HSPHR injections reduce cartilage damage, synovial hyperplasia, and bone sclerosis in post-traumatic OA.
- The treatment enhances selenoprotein synthesis and activates the PI3K-AKT-mTOR pathway in key cells.
- The approach reveals shared regulatory pathways among different cell types in OA.

## Abstract

Osteoarthritis (OA) involves multiple pathological processes and presents significant clinical challenges in treatment. Traditional therapies focus on individual factors in cartilage, synovium, or subchondral bone, limiting their ability to comprehensively address OA pathogenesis. In this study, a ROS/MMP13 dual-responsive organic selenium hydrogel microsphere (HSPHR) is developed to trigger a localized microenvironmental response specific to early OA by exploiting the disease’s pathological features. Simultaneously, the organic selenium component effectively enhances selenoprotein levels in cartilage, synovium, and subchondral bone, enabling multimodal treatment for osteoarthritis. HSPHR injections into joints reduce cartilage damage, synovial hyperplasia, and bone sclerosis in post-traumatic OA, while promoting new cartilage in defect models. It enhances selenoprotein synthesis and activates the PI3K-AKT-mTOR pathway in key cells, improving mitochondrial function and antioxidant capacity, thus reversing OA-related changes. Here, we present a multimodal therapeutic strategy for OA lesions and reveal shared regulatory pathways among different cell types. This approach offers distinct insights for the multimodal treatment of degenerative joint diseases.

Osteoarthritis encompasses multiple pathological processes making it difficult to treat. Here, the authors develop ROS/MMP13 dual-responsive organic selenium hydrogel microspheres (HSPHR) to modulate intra-articular multi-tissue selenoprotein levels, achieving multimodal treatment.