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pH-Responsive Engineered Exosomes Enhance Endogenous Hyaluronan Production by Reprogramming Chondrocytes for
Xiaodan Wu1,2, Weiyong Tao1,2, Ziyang Lan1,2
1Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China.
Advanced Healthcare Materials
|March 5, 2025
Summary
Engineered exosomes deliver hyaluronan synthase 2 (HAS2) to chondrocytes, enabling sustained production of endogenous hyaluronic acid (HA) for cartilage repair. This novel approach offers a potential one-shot treatment for osteoarthritis, outperforming multiple exogenous HA injections.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Molecular Biology
Background:
- Cartilage injury from trauma or inflammation causes joint dysfunction and pain.
- Current treatments using exogenous hyaluronic acid (HA) require multiple injections due to short in vivo duration.
Purpose of the Study:
- To develop a novel strategy for in situ chondrocyte reprogramming to produce endogenous high molecular weight HA.
- To create pH-responsive engineered exosomes for targeted delivery of hyaluronan synthase 2 (HAS2) to chondrocytes.
Main Methods:
- Engineered exosomes decorated with VSV-G and HAS2 were developed.
- VSV-G mediated pH-triggered membrane fusion for HAS2 delivery to chondrocyte membranes, avoiding lysosomal degradation.
- Characterization of HAS2-chondrocytes for endogenous HA production in vitro and in vivo.
Main Results:
- Engineered exosomes successfully generated HAS2-chondrocytes producing high molecular weight HA.
- One-shot administration of engineered exosomes increased intra-articular HA concentration by 145% compared to exogenous HA.
- Endogenous HA levels were sustained for 4 weeks, while exogenous HA decreased within 2 weeks, enhancing cartilage regeneration and inhibiting osteoarthritis progression.
Conclusions:
- pH-responsive engineered exosomes offer a promising platform for sustained endogenous HA generation.
- This approach has significant potential to replace multiple exogenous HA injections for effective cartilage repair.
- The strategy effectively treats osteoarthritis by promoting cartilage regeneration through sustained HA production.
