Prenatal exposure to famine remarkably increases hyperglycemia risk in 2 consecutive generations of Chinese adults independent of known T2D risk factors, which supports the notion that prenatal nutrition plays an important role in the development of T2D across consecutive generations of Chinese adults. This trial was registered at www.chictr.org.cn as ChiCTR-ECH-13003644.

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Reconstruction of the knee meniscus remains a significant clinical challenge owing to its complex anisotropic tissue organization, complex functions, and limited healing capacity in the inner region. The development of in situ tissue-engineered meniscal scaffolds, which provide biochemical signaling to direct endogenous stem/progenitor cell (ESPC) behavior, has the potential to revolutionize meniscal tissue engineering. In this study, a fiber-reinforced porous scaffold was developed based on aptamer Apt19S-mediated mesenchymal stem cell (MSC)-specific recruitment and dual growth factor (GF)-enhanced meniscal differentiation. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized meniscus extracellular matrix (MECM) and then mixed with gelatin methacrylate (GelMA) to form a photocrosslinkable hydrogel. Second, connective tissue growth factor (CTGF)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and transforming growth factor-β3 (TGF-β3)-loaded PLGA microparticles (MPs) were mixed with aptamer-conjugated MECM to simulate anisotropic meniscal regeneration. These three bioactive molecules were delivered sequentially. Apt19S, which exhibited high binding affinity to synovium-derived MSCs (SMSCs), was quickly released to facilitate the mobilization of ESPCs. CTGF incorporated within PLGA NPs was released rapidly, inducing profibrogenic differentiation, while sustained release of TGF-β3 in PLGA MPs remodeled the fibrous matrix into fibrocartilaginous matrix.The in vitro results showed that the sequential release of Apt19S/GFs promoted cell Li Hao, Zhao Tianyuan, and Cao Fuyang contributed equally to this study.