Researchers have developed a nanozyme-integrated hydrogel that directly targets advanced glycation end products (AGEs), a key driver of diabetic osteoarthritis (DOA).
Study: Nanozyme-Integrated Hydrogel Targeting AGEs for Diabetic Osteoarthritis Therapy. Image Credit: Dragana Gordic/Shutterstock.com
The study, published in Advanced Science, demonstrates how a locally delivered, photothermally activated biomaterial can slow joint degeneration, restore cartilage function, and improve mobility in diabetic animal models.
Diabetic osteoarthritis is increasingly recognized as a distinct and more aggressive form of osteoarthritis. Chronic hyperglycemia accelerates the accumulation of AGEs, the damaging compounds formed when sugars bind to proteins, which drive oxidative stress, inflammation, cartilage breakdown, and impaired joint lubrication.
Current clinical treatments, including analgesics and intra-articular steroids, focus primarily on pain relief. They do not address AGE accumulation or the downstream cellular damage that makes DOA difficult to manage, particularly in diabetic patients.
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Building a Targeted Hydrogel Therapy
Looking to address these challenges, the research team engineered a composite hydrogel known as PTC-MP. The material integrates polydopamine-coated tannic acid–cerium nanozymes (PTC) into a sodium alginate-Poloxamer 407 matrix, reinforced with magnesium ions (Mg2+).
Each component plays a distinct role. Tannic acid helps suppress AGE formation, cerium nanozymes mimic antioxidant enzymes to neutralize reactive oxygen species, and magnesium ions promote endogenous hyaluronic acid production, improving joint lubrication. Polydopamine enables mild photothermal therapy (mPTT) under near-infrared (NIR) light.
The hydrogel is injectable, mechanically stable, and designed to conform to irregular joint cavities, making it suitable for intra-articular delivery.
Under controlled NIR irradiation, the hydrogel warms to approximately 40-42 °C, a temperature range known to be beneficial for osteoarthritis treatment.
This mild heating enhances cellular uptake of the nanozymes and boosts their catalytic activity without damaging surrounding tissue.
The photothermal effect also induces heat shock protein 70 (HSP70), a protective molecule that reduces inflammation, limits cell death, and helps stabilize mitochondrial function in cartilage cells.
Hydrogel Therapy: Does it Work?
In laboratory experiments, the hydrogel inhibited AGE formation by up to 43.6 % at optimal cerium concentrations.
This effect arises from three complementary mechanisms: scavenging reactive oxygen and nitrogen species, chelating pro-glycation metal ions such as Fe2+, and competitively blocking protein glycation sites.
Chondrocytes treated with the hydrogel showed lower oxidative stress, restored mitochondrial activity, and increased expression of key cartilage markers, including collagen II and aggrecan. These findings indicate recovery of cartilage homeostasis rather than temporary symptom relief.
Beyond cartilage protection, the hydrogel addresses lubrication failure, a major contributor to joint wear in DOA.
In fibroblast-like synoviocytes, treatment reduced inflammatory signaling and restored the activity of hyaluronic acid synthase-2 (HAS-2). Magnesium ions further stimulated hyaluronic acid secretion, improving the biochemical environment of the joint.
The therapy was tested in streptozotocin-induced diabetic rats with surgically induced osteoarthritis, a model that reflects severe diabetic joint pathology. Although the authors note this represents Type 1 diabetes rather than the more common Type 2 form, the results were striking.
Micro-CT imaging revealed preserved joint architecture and reduced subchondral bone erosion in treated animals. Histological analysis showed reduced inflammation and maintenance of cartilage matrix.
Functional testing confirmed near-normal gait patterns, with treated rats achieving step lengths similar to healthy controls.
A “3R” Strategy for Diabetic Osteoarthritis
The researchers describe their approach as a “3R” strategy:
- Restrain AGE formation
- Restore cartilage homeostasis
- Reinforce joint repair through improved lubrication
This multi-layered design distinguishes the therapy from previous treatments that have focused primarily on inflammation or pain.
Importantly, the hydrogel demonstrated strong biocompatibility. It remained in the joint cavity for up to 14 days, showed no accumulation in major organs, and caused no detectable tissue damage in safety studies.
The authors note that further work is needed to evaluate long-term biodegradation, ion release, and performance in models of Type 2 diabetes.
However, the study establishes a compelling proof of concept for AGE-targeted, nanozyme-based therapies.
The Study Beyond Osteoarthritis
By directly addressing AGE-driven pathology, this work may open new possibilities for treating other diabetic complications marked by oxidative stress and chronic inflammation.
More broadly, it highlights how innovative biomaterials can combine catalytic activity, mechanical support, and external activation to tackle complicated degenerative diseases.
Journal Reference
Chen, R. et al. (2025, December). Nanozyme-Integrated Hydrogel Targeting AGEs for Diabetic Osteoarthritis Therapy. Advanced Science, e16389. DOI: 10.1002/advs.202516389
