Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration

TLDR

Osteoarthritis is marked by mitochondrial dysfunction and oxidative stress, and although MSC‑derived exosomes mediate intercellular mitochondrial communication, their capacity to modulate mitochondrial function in OA has not been investigated. The study aimed to evaluate the therapeutic potential of MSC exosomes delivered via a 3D‑printed scaffold for early osteoarthritis treatment. The authors examined mitochondrial proteins in human cartilage, confirmed exosome‑induced mitochondrial biogenesis in vitro, engineered a radially oriented ECM/GelMA/exosome scaffold using desktop stereolithography, and tested its osteochondral repair efficacy in a rabbit model. The scaffold restored chondrocyte mitochondrial function, promoted migration, shifted macrophages to an M2 phenotype, and significantly accelerated cartilage regeneration in the rabbit model, indicating its promise for early OA therapy.

Abstract

Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods: We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro. We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results: The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion: This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.