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Organic di-selenide hydrogel microspheres for multimodal treatment of osteoarthritis
Yang Liu1,2, Yijian Zhang1,2, Chenqi Yu1,2
1Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
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.
Insights
A novel organic selenium hydrogel microsphere (HSPHR) offers multimodal treatment for osteoarthritis (OA). This therapy targets the joint
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Osteoarthritis Pathogenesis
Background:
- Osteoarthritis (OA) presents complex challenges due to its multifactorial nature, with current treatments often targeting isolated pathological aspects.
- Existing therapies struggle to comprehensively address the interconnected pathological processes in cartilage, synovium, and subchondral bone.
- Developing integrated therapeutic strategies is crucial for effective OA management.
Purpose of the Study:
- To develop a dual-responsive organic selenium hydrogel microsphere (HSPHR) for targeted, multimodal osteoarthritis treatment.
- To investigate HSPHR's ability to respond to the early OA microenvironment and enhance selenoprotein levels.
- To evaluate the therapeutic efficacy of HSPHR in preclinical osteoarthritis models.
Main Methods:
- Fabrication of ROS/MMP13 dual-responsive organic selenium hydrogel microspheres (HSPHR).
- Intra-articular injection of HSPHR in post-traumatic and defect osteoarthritis models.
- Assessment of cartilage integrity, synovial hyperplasia, bone sclerosis, and new cartilage formation.
- Analysis of selenoprotein synthesis, PI3K-AKT-mTOR pathway activation, mitochondrial function, and antioxidant capacity.
Main Results:
- HSPHR injections significantly reduced cartilage damage, synovial hyperplasia, and bone sclerosis in post-traumatic OA models.
- HSPHR promoted new cartilage formation in defect models.
- The treatment enhanced selenoprotein synthesis and activated the PI3K-AKT-mTOR pathway, improving mitochondrial function and antioxidant capacity.
- HSPHR effectively reversed OA-related cellular and tissue changes.
Conclusions:
- HSPHR provides a promising multimodal therapeutic strategy for osteoarthritis lesions.
- The study reveals shared regulatory pathways (PI3K-AKT-mTOR) involved in OA pathogenesis across different cell types.
- This approach offers novel insights for treating degenerative joint diseases.
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