De Martino Selene, Cavalli Silvia, Netti Paolo Antonio
Center for Advanced Biomaterials for Healthcare, IIT@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci, 53, Napoli, 80125, Italy.
Interdisciplinary Research Centre on Biomaterials (CRIB) and Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale, DICMAPI, Università degli Studi di Napoli Federico II, Piazzale Tecchio, 80, Napoli, 80125, Italy.
Adv Healthc Mater. 2020 Jul;9(13):e2000470. doi: 10.1002/adhm.202000470. Epub 2020 May 19.
Patterned surfaces have proved effective in guiding stem cells commitment to a specific lineage by presenting highly ordered biophysical/biochemical cues at the cellmaterial interface. Their potency in controlling cell fate can be significantly empowered by encoding logic of space and time control of signal presentation. Here, azopolymeric photoactive interfaces are proposed to present/withdraw morphophysical signals to living cells using a green light trigger in a non-invasive spatio-temporal controlled way. To assess the potency of these dynamic platforms in controlling cell decision and fate, topography changes are actuated by light at specific times to reverse the fate of otherwise committed human mesenchymal stem cells (hMSC) toward osteoblastic lineage. It is first proved by dynamic change from ordered parallel patterning to flat or grid surfaces, that it is possible to induce cyclic cellular and nuclear stretches. Furthermore, by culturing hMSCs on a specific pattern known to prime them toward osteoblast lineage, the possibility to reroute or reverse stem cell fate decision by dynamic modulation of morphophysical signal is proved. To conclude, dynamic topographies can control the spatial conformation of hMSCs, modulate lineage reversal even after several weeks of culture and redirect lineage specification in response to light-induced changes in the microenvironment.
通过在细胞与材料界面呈现高度有序的生物物理/生物化学线索,图案化表面已被证明在引导干细胞定向分化为特定谱系方面是有效的。通过对信号呈现的空间和时间控制进行编码,它们在控制细胞命运方面的效力可以得到显著增强。在此,提出了偶氮聚合物光活性界面,以非侵入性的时空控制方式,利用绿光触发向活细胞呈现/撤回形态物理信号。为了评估这些动态平台在控制细胞决策和命运方面的效力,在特定时间用光激活地形变化,以逆转原本已定向分化为成骨细胞谱系的人间充质干细胞(hMSC)的命运。首先通过从有序平行图案化到平坦或网格表面的动态变化证明,有可能诱导细胞和细胞核的周期性拉伸。此外,通过在已知能促使hMSC向成骨细胞谱系分化的特定图案上培养hMSC,证明了通过动态调节形态物理信号来重新引导或逆转干细胞命运决定的可能性。总之,动态地形可以控制hMSC的空间构象,即使在培养数周后也能调节谱系逆转,并响应光诱导的微环境变化重新引导谱系特化。