Researchers develop novel engineered extracellular matrix to improve cartilage repair

Recently, a research team from Chongqing Medical University, led by Prof. Wei Huang, Dr. Wei Bao, and Dr. Yiting Lei, has successfully developed a novel engineered extracellular matrix (eECM) to address the challenge of cartilage repair. Their findings were published in Research under the title "Cytokine-Activated MSC-Derived ECM Facilitates Cartilage Repair by Maintaining Chondrocyte Homeostasis and Promoting Chondrogenic Differentiation of Recruited Stem Cells."

Research background

Cartilage injuries are a common clinical issue, often caused by trauma, severe infections, or degenerative joint diseases. The lack of direct blood supply to cartilage and limited access to nutrients from the surrounding synovial fluid make it difficult for these injuries to heal on their own, often leading to osteoarthritis, which is characterized by joint deformity and functional impairment. Current strategies for cartilage repair, such as microfracture surgery, arthroscopic debridement, and cell-based therapies, face challenges including limited cell availability, risks of immune rejection, donor site morbidity, and logistical issues related to cell transport.

Research progress

The research team optimized the extracellular matrix (ECM) derived from mesenchymal stromal cells (MSCs) by preconditioning them with inflammatory cytokines, such as IL-6, TNF-α, and IFN-γ, to create a bioactive eECM. Immunofluorescence and scanning electron microscopy revealed that the decellularization process successfully removed cellular components while preserving key ECM components, including glycosaminoglycans (GAGs).

Further proteomic analysis showed significant changes in the expression levels of key ECM components, such as collagen, laminin, and matrix metalloproteinases, in the cytokine-preconditioned eECM. The eECM was also enriched with bioactive molecules like TGFBI, TGFB3, and SDF2, which play crucial roles in maintaining chondrocyte homeostasis and recruiting endogenous stem cells.

In vitro experiments demonstrated that the eECM significantly influenced the expression of cartilage matrix components. Specifically, IFN-γ-ECM restored type II collagen levels and reduced ADAMTS5 expression, promoting matrix synthesis and inhibiting degradation, thereby effectively maintaining cartilage homeostasis. Additionally, the eECM significantly enhanced chondrocyte recruitment and proliferation, with IFN-γ-ECM showing the strongest recruitment ability. It also reduced pro-inflammatory cytokine levels and enhanced chondrocyte proliferation, indicating significant anti-inflammatory effects and the potential to reverse cellular senescence.

In vivo experiments using an animal model showed that implanting IFN-γ-ECM into cartilage defects treated with microfracture surgery led to significantly better cartilage regeneration compared to controls treated with microfracture alone or with standard ECM. Histological analysis at 6 and 12 weeks post-surgery revealed that the IFN-γ-ECM group had superior hyaline cartilage regeneration, with repaired tissue showing rich type II collagen expression and minimal distinction from surrounding normal tissue.

Future prospects

This study not only provides a new strategy for cartilage repair but also offers new insights into the development of bioactive materials with specific functions. By selecting appropriate cytokines for MSC preconditioning, it is possible to customize eECMs with specific functions for cartilage repair and other tissue regeneration therapies. Future research will further explore the long-term safety and efficacy of eECM in vivo, as well as its potential applications in other tissue regeneration fields.