Engineering the meniscus is challenging due to its bizonal structure; the tissue is cartilaginous at the inner portion and fibrous at the outer portion. Here, we constructed an artificial meniscus mimicking the biochemical organization of the native tissue by 3D printing a meniscus shaped PCL scaffold and then impregnating it with agarose (Ag) and gelatin methacrylate (GelMA) hydrogels in the inner and outer regions, respectively. After incubating the constructs loaded with porcine fibrochondrocytes for 8 weeks, we demonstrated that presence of Ag enhanced glycosaminoglycan (GAG) production by about 4 fold (p < 0.001), while GelMA enhanced collagen production by about 50 fold (p < 0.001). In order to mimic the physiological loading environment, meniscus shaped PCL/hydrogel constructs were dynamically stimulated at strain levels gradually increasing from the outer region (2% of initial thickness) towards the inner region (10%). Incorporation of hydrogels protected the cells from the mechanical damage caused by dynamic stress. Dynamic stimulation resulted in increased ratio of collagen type II (COL 2) in the Ag-impregnated inner region (from 50% to 60% of total collagen), and increased ratio of collagen type I (COL 1) in the GelMA-impregnated outer region (from 60% to 70%). We were able to engineer a meniscus, which is cartilage-like at the inner portion and fibrocartilage-like at the outer portion. Our construct has a potential for use as a substitute for total meniscus replacement.

No abstract

Cardiovascular diseases are the leading cause of death worldwide and their occurrence is highly associated with age. However, lack of knowledge in cardiac tissue aging is a major roadblock in devising novel therapies. Here, we studied the effects of cell and cardiac extracellular matrix (ECM) aging on the induced pluripotent stem cell (iPSC)-derived cardiomyocyte cell state, function, as well as response to myocardial infarction (MI)-mimicking stress conditions in vitro.Within 3-weeks, young ECM promoted proliferation and drug responsiveness in young cells, and induced cell cycle re-entry, and protection against stress in the aged cells. Adult ECM improved cardiac function, while aged ECM accelerated the aging phenotype, and impaired cardiac function and stress defense machinery of the cells. In summary, we have gained a comprehensive understanding of cardiac aging and highlighted the importance of cell-ECM interactions. This study is the first to investigate the individual effects of cellular and environmental aging and identify the biochemical changes that occur upon cardiac aging.

No abstract

No abstract