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    Facile calcium ion-regulated grafting of dense and highly stretched hyaluronan for selective mediation of cancer cells rolling under high-speed flow

    Journal: Acta Biomater., Volume 146, JUL 1, page 177–186

    Authors: Xu, Ting; Han, Lulu; Jia, Lingyun

    Organizations: Na-tional Natural Science Foundation of China [52173116]; NSFC-Liaoning United Fund [U20A20263]; National Natural Science Foundation of China [51773026]; Liao Ning Revitalization Talents Program [XLYC1907189]; Fundamental Research Funds for the Central Universities [DUT20LAB121, DUT20YG107, DUT21YG122]

    Keywords: Hyaluronan; Cancer cell rolling; High density; Conformation; CD44

    The development of materials that selectively mediate the rolling of cancer cells is important for the high-throughput enrichment of high-speed cancer cells. Here we constructed a dense and stretched low molecular weight hyaluronic acid (HA(9.6k))-modified surface to selectively promote the rolling of CD44-high cancer cells. The HA surface (calcium ion-regulated HA(9.6k) surface, Ca-rHA) was fabricated via a calcium ion-regulated method, where calcium ion incorporation induced the shrink of HA(9.6k) chains to achieve the highest reported grafting density of about 2.73 +/- 0.20 x 10(4) HA chains mu m(-2). Upon the removal of calcium ions, the dense HA(9.6k) chains switched to a highly stretched conformation. The high density and flexibility of Ca-rHA bearing abundant binding sites enhanced the rolling of CD44-high cancer cells and reduced the velocity of cells from 1389 mu m s(-1) to 99 mu m s(-1) (7%), comparable to that of the physiological rolling event and outperforming traditional grafting-to HA and E-selectin, without causing phenotypic changes. When processing complex samples under high-speed flow, Ca-rHA selectively mediated the rolling of cancer cells and enriched their ratio to peripheral blood mononuclear cells from 1:1 to 15:1. As the only reported artificial biomaterial capable of selectively mediating the rolling of cancer cells under a physiological high-speed flow, Ca-rHA holds promise in enriching intact cells for downstream analysis in the clinics by encouraging the surface-cell contacts. Statement of significance The development of materials that selectively mediate the rolling of cancer cells is important for the high-throughput enrichment of cancer cells rolling under high-speed flow, yet is less reported. To selectively promote the rolling of cancer stem cell marker CD44-high cancer cells, a surface with dense and stretched low molecular weight hyaluronic acid (HA(9.6k)) was constructed. With Ca2+ regulation, HA(9.6k) chains shrank to achieve the highest reported grafting density of 2.73 +/- 0.20 x 10(4) chains mu m(-2) and further switched to a highly stretched conformation after the removal of Ca2+ ions. As the only reported artificial biomaterial capable of selectively mediating the rolling of cancer cells under a physiological high-speed flow, this Ca2+-regulated HA(9.6k) surface holds promise in enriching intact cells for downstream analysis in the clinics. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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