Fabrication of a cartilage patch by fusing hydrogel-derived cell aggregates onto electrospun film

Irregular defects at sites of degenerative cartilage often accompany osteoarthritis (OA). The development of novel cell-/biomaterial-based cartilage tissue engineering methods to address these defects may provide a durable approach to hinder the development of OA. In this study, we fabricated a neocartilage patch by fusing cell aggregates onto a biodegradable nanofiber film for degenerative cartilage repair. Human mesenchymal stem/stromal cell (MSC) aggregates were prepared and induced for chondrogenesis in a thermosensitive hydrogel, poly (N-isopropylacrylamide-co-acrylic acid (p(NIPAAm-AA)). Cell migration mediated the formation of cell aggregates in the thermosensitive hydrogel and led to a cell-dense hollow shell structure. The chondrocytes derived from MSC aggregates in the hydrogel were evidenced by the expression of chondrogenesis-related genes and extracellular matrices. They were fused onto an electrospun film by mechanical force and spatial confinement to generate a neo-cartilage patch. The fabricated neocartilage patches may be able to integrate into the irregular defects under compressive stresses and achieve cartilage regeneration in vivo. The formation of human mesenchymal stem/stromal cells aggregates in thermosensitive hydrogels was mechanistically examined. These in situ formed cell aggregates with enhanced chondrogenesis were bioengineered into a neocartilage patch for regeneration of superficial irregular cartilage defects.