High-density ZnO nanowires for cellular biointerfaces: a new role as myogenic differentiation switch

The design of artificial platforms for expanding undifferentiated stem cells is of tremendousimportance for regenerative medicine [1]. We have recently demonstrated that a ZnO nanowires(NWs) decorated glass support permits to obtain a differentiation switch during proliferation formesoangioblasts (MABs)– i.e. multipotent progenitor cells which are remarkable candidates for thetherapy of muscle diseases [2]. We have optimized the ZnO NWs synthesis on glass surfaces bynumerical simulations and experimental systematic investigations, considering zinc speciation andsupersaturation [3]. In particular, we demonstrated by numerical simulations that the ligandethylenediamine, at the isoelectric point of the ZnO NWs tips, can effectively control – at 1:1stoichiometric ratio with zinc – both speciation and supersaturation of zinc in the nutrient solution.In this regard, we employed ethanolamine (a safer precursor) for in-situ producing ethylenediamineby means of a zinc-catalysed amination reaction of ethanolamine by ammonia. The obtained highqualityZnONWs-cells biointerface allows cells to maintain viability and a spherical viableundifferentiated state during the 8 days observation time. Simulations of the interface by theoreticalmodels [4] and our experimental investigations by SEM and confocal microscopy demonstrate thatNWs do not induce any damage on the cellular membrane, whilst blocking their differentiation. Morespecifically, the myosin heavy chain, typically expressed in differentiated myogenic progenitors, iscompletely absent. Interestingly, the differentiation capabilities are completely restored upon cellremoval from the NW-functionalized substrate and regrowing onto a standard culture glass dish.These results open the way towards unprecedented applications of ZnO NWs for cell-based therapyand tissue engineering [5].References[1] G. Cossu, P. Bianco, Curr. Opin. Genet. Dev. 2003, 13, 537-542.[2] V. Errico, G. Arrabito, E. Fornetti, C. Fuoco, S. Testa, G. Saggio, S. Rufini, S. M. Cannata, A.Desideri, C. Falconi, C. Gargioli, ACS Appl. Mater. Interfaces, 2018, 10, 14097- 14107.[3] G. Arrabito, V. Errico, Z. Zhang, W. Han, C. Falconi, Nano Energy, 2018, 46, 54-62.[4] N. Buch-Månson, S. Bonde, J. Bolinsson, T. Berthing, J. Nygård, K.L. Martinez, Adv. Funct.Mater. 2015, 25, 3246-3255.[5] Y. Su, I. Cockerill, Y. Wang, Y.-X. Qin, L. Chang, Y. Zheng, and D. Zhu, Trends inBiotechnology, 2019, 37, 428-441.