Abstract
Artificial cell spheroids are gaining importance in tissue engineering and regenerative medicine fields. Biomimetic construction of stem cell spheroids is nevertheless challenging, and bioplatforms permitting controllable and high-efficient fabrication of functional stem cell spheroids are needed. Here, a fractal nanofiber-based bioplatform is developed based on a tunable interfacial-induced crystallization approach, allowing a programmed culture of artificial stem cell spheroids under an ultralow cell seeding density. Specifically, starting with the nanofibers of poly(L-lactide) (PLLA) and gelatin (PmGn), an interfacial growth of PLLA nanocrystals is subsequently performed to construct the fractal nanofiber-based biotemplates (C-PmGn). Cell experiments with human dental pulp stem cells (hDPSCs) demonstrate that the fractal C-PmGn could effectively decrease cell-matrix interactions, thus facilitating spontaneous cell spheroid formation even under a low cell seeding density (1 × 104 cells/cm2). Nanotopological properties of the C-PmGn bioplatform can be tuned by adjusting the fractal degree, thus enabling its suitability for the 3D culture of diverse hDPSC spheroids. Such a strategy provides a relatively simple and low-cost option for formation, expansion, and utility of stem cell spheroids. It offers another promising pathway to advance the development of stem cell therapies.
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