In a groundbreaking development that could revolutionize cartilage repair and osteoarthritis treatment, researchers have created a biomimetic gradient-structured cartilage organoid (BGSC-organoid) culture system. This innovative approach, detailed in a study published in *Bioactive Materials* (which translates to *生物活性材料* in English), offers a promising avenue for joint regeneration and could have significant implications for the construction and energy sectors, particularly in areas requiring advanced biomaterials and regenerative technologies.
The study, led by Xiangwan Miao from the Department of Otolaryngology & Head and Neck Surgery at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and affiliated with the Department of Orthopedic Surgery at Shanghai Ninth People’s Hospital and the Wake Forest Institute for Regenerative Medicine, focuses on addressing the challenges posed by articular cartilage damage. This damage is a primary cause of osteoarthritis (OA), often resulting from a senescent cartilage microenvironment and insufficient repair of chondrocytes. The limited availability and depleted stemness phenotype of chondrocyte stem cells have historically hindered effective cartilage repair, exacerbating symptoms and limiting treatment options.
Miao and his team developed the BGSC-organoid culture system using decellularized cartilage extracellular matrix infused with extracellular vesicles from SOX9-overexpressing bone marrow-derived stem cells (SBEVs). This system induces the rejuvenation of senescent chondrocytes, a critical step in cartilage repair. “Single-cell sequencing revealed that a subpopulation of chondrocytes could be rejuvenated in the BGSC-organoid culture system,” Miao explained. This finding highlights the potential of the BGSC-organoids to restore cartilage function and delay degeneration.
To simulate the mechanical microenvironment of cartilage, the researchers constructed an ex vivo osteoarthritis-on-a-chip (OAOC) model with cyclic mechanical stimulation. The BGSC-organoids demonstrated sustained release of chondrocyte-protective factors and good mechanical resistance through the Vimentin/14-3-3/FOXO3 pathway. Animal studies further showed that BGSC-organoids preserved a hyaline-like cartilage phenotype in vivo and delayed the degeneration of articular cartilage and intervertebral discs.
The implications of this research extend beyond medical applications. In the construction industry, advanced biomaterials like BGSC-organoids could lead to innovative solutions for joint regeneration in orthopedic implants and prosthetics. The energy sector could also benefit from the development of bio-inspired materials with enhanced durability and regenerative capabilities, potentially improving the performance and longevity of various energy-related infrastructures.
As the field of regenerative medicine continues to evolve, the efficient expansion of human cartilage organoids with enhanced regenerative capabilities represents a promising approach for joint regeneration. This research not only advances our understanding of cartilage repair but also paves the way for future developments in biomaterials and regenerative technologies, offering hope for improved treatments and innovative applications across multiple industries.