title: Engineering of cell membranes with a bisphosphonate-containing polymer using ATRP synthesis for bone targeting.
abstract: The field of polymer-based membrane engineering has expanded since we first demonstrated the reaction of N-hydroxysuccinimide ester-terminated polymers with cells and tissues almost two decades ago. One remaining obstacle, especially for conjugation of polymers to cells, has been that exquisite control over polymer structure and functionality has not been used to influence the behavior of cells. Herein, we describe a multifunctional atom transfer radical polymerization initiator and its use to synthesize water-soluble polymers that are modified with bisphosphonate side chains and then covalently bound to the surface of live cells. The polymers contained between 1.7 and 3.1 bisphosphonates per chain and were shown to bind to hydroxyapatite crystals with kinetics similar to free bisphosphonate binding. We engineered the membranes of both HL-60 cells and mesenchymal stem cells in order to impart polymer-guided bone adhesion properties on the cells. Covalent coupling of the polymer to the non-adherent HL-60 cell line or mesenchymal stem cells was non-toxic by proliferation assays and enhanced the binding of these cells to bone.
authors.affiliation: The Institute for Complex Engineered Systems, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: D'Souza
authors.affiliation: The Institute for Complex Engineered Systems, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Murata
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA 15219, USA; PolyOne Technology & Innovation Center, 11650 Lake Side Crossing Court, St Louis, MO 63146, USA.
authors.forename: Moncy V
authors.initials: MV
authors.lastname: Jose
authors.affiliation: Department for Bioengineering, Cell Technologies, and Cell Therapy, Center for Life Sciences, Nazarbayev University, 53 Kabanbay Batyr Ave, Astana 010000, Kazakhstan.
authors.forename: Sholpan
authors.initials: S
authors.lastname: Askarova
authors.affiliation: Department for Bioengineering, Cell Technologies, and Cell Therapy, Center for Life Sciences, Nazarbayev University, 53 Kabanbay Batyr Ave, Astana 010000, Kazakhstan.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Yantsen
authors.affiliation: The Institute for Complex Engineered Systems, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA.
authors.forename: Jill D
authors.initials: JD
authors.lastname: Andersen
authors.affiliation: The Institute for Complex Engineered Systems, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA.
authors.forename: Collin D J
authors.initials: CD
authors.lastname: Edington
authors.affiliation: The Institute for Complex Engineered Systems, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Clafshenkel
authors.affiliation: The Institute for Complex Engineered Systems, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Koepsel
authors.affiliation: The Institute for Complex Engineered Systems, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA. Electronic address: alanrussell+@cmu.edu.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Russell
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004164:Diphosphonates / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013388:Succinimides / Q000737:chemistry; D013499:Surface Properties / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D004164:Diphosphonates; D011108:Polymers; D013388:Succinimides; C001426:N-hydroxysuccinimide
keywords: ATRP; Bone targeting polymer; Cell reactive polymers; Membrane engineering