4.1 Article

Short-term exposure to TNF-α promotes odontogenesis of stem cells of apical papilla on nanofibrous poly(L-lactic acid) scaffolds

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MATERIALIA
卷 32, 期 -, 页码 -

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ELSEVIER SCI LTD
DOI: 10.1016/j.mtla.2023.101951

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Cytokine; Inflammation; Stem cells of apical papilla (SCAP); Nanofibrous poly(L-lactic acid) (PLLA) scaffold; Differentiation; Dentin regeneration

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This study investigated the effect of TNF-alpha preconditioning on the proliferation and differentiation of stem cells on a 3D scaffold. The results showed that preconditioning with TNF-alpha enhanced cellular activity and mineralization. Additionally, the use of nanofiber scaffolds further promoted mineralized tissue formation and gene expression.
The aim of this study was to investigate the effect of short-term (3 days) preconditioning with pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) on proliferation and odontogenic differentiation of stem cells of apical papilla (SCAP) seeded on a 3D scaffold. Our results showed that while TNF-alpha preconditioning at various concentrations did not affect SCAP proliferation, it enhanced alkaline phosphatase (ALP) activity and mineralized matrix deposition in culture. Preconditioning SCAP using TNF-alpha at a concentration of about 1 ng/ml optimally enhanced odontogenic gene expression of SCAP in culture. Highly porous nanofibrous (NF) poly(L- lactic acid) (PLLA) scaffolds, with nanofiber features mimicking the environment of the extracellular matrix, were fabricated using a thermally induced phase separation method. TNF-alpha preconditioning of SCAP at 1 ng/ml promoted ALP activity, calcium deposition and mineralized tissue formation of SCAP cultured on 3D NF-PLLA scaffolds in vitro. Moreover, TNF-alpha preconditioning at a concentration of 1 ng/ml promoted the formation of more mineralized tissue as well as stronger DSPP expression of SCAP seeded on NF-PLLA scaffolds in vivo. Collectively, this study suggests that short term TNF-alpha preconditioning, mimicking the transiently low concentration TNF-alpha present during inflammation, may serve as a feasible approach to enhance the odontogenic differentiation of stem/progenitor cells on a biomimetic scaffold for 3D dentin regeneration. These results present a first step in the development of a dental tissue engineering strategy where odontogenesis is enhanced by modulating inflammation.

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