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Polymer microparticles with defined surface chemistry and topography mediate the formation of stem cell aggregates and cardiomyocyte function

Alvarez-Paino, Marta; Amer, Mahetab H.; Nasir, Aishah; Cuzzucoli Crucitti, Valentina; Needham, David; Denning, Chris; Alexander, Morgan R.; Rose, Felicity; Alexander, Cameron


Marta Alvarez-Paino

Mahetab H. Amer

Aishah Nasir

Valentina Cuzzucoli Crucitti

David Needham

Chris Denning

Morgan R. Alexander

Felicity Rose

Cameron Alexander


Surface-functionalized microparticles are relevant to fields spanning engineering and biomedicine, with uses ranging from cell culture to advanced cell delivery. Varying topographies of biomaterial surfaces are also being investigated as mediators of cell-material interactions and subsequent cell fate. To investigate competing or synergistic effects of chemistry and topography in three-dimensional (3D) cell cultures, methods are required to introduce these onto microparticles without modification of their underlying mor-phology or bulk properties. In this study, a new approach for surface functionalization of poly(lactic acid) (PLA) microparticles is reported that allows decoration of the outer shell of the polyesters with additional polymers via aqueous atom transfer radical polymerization (ATRP) routes. PLA microparticles with smooth or dimpled surfaces were functionalized with poly(poly(ethylene glycol) methacrylate) (pPEG-MA) and poly[N-(3-aminopropyl)methacrylamide] (pAPMA) brushes, chosen for their potential abilities to mediate cell adhesion. X-ray Photoelectron Spectroscopy (XPS) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis indicated homogeneous coverage of the microparticles with pol-ymer brushes while maintaining the original topographies. These materials were used to investigate the relative importance of surface chemistry and topography both on the formation of human immortalized mesenchymal stem cell (hiMSCs) particle-cell aggregates and on the enhanced contractility of cardiomyo-cytes derived from human induced pluripotent stem cells (hiPSC-CMs). The influence of surface chemis-try was found to be more important on the size of particle-cell aggregates than topographies. In addition, surface chemistries that best promoted hiMSC attachment also improved hiPSC-CM attachment and con-tractility. These studies demonstrated a new route to obtain topo-chemical combinations on polyester-based biomaterials, and provided clear evidence for the predominant effect of surface functionality over micron-scale dimpled topography in cell-microparticle interactions. These findings thus provide new guiding principles for the design of biomaterial interfaces to direct cell function.

Journal Article Type Article
Publication Date Sep 25, 2019
Journal ACS Applied Materials & Interfaces
Print ISSN 1944-8244
Electronic ISSN 1944-8252
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 11
Issue 38
Pages 34560-34574
APA6 Citation Alvarez-Paino, M., Amer, M. H., Nasir, A., Cuzzucoli Crucitti, V., Needham, D., Denning, C., …Alexander, C. (2019). Polymer microparticles with defined surface chemistry and topography mediate the formation of stem cell aggregates and cardiomyocyte function. ACS Applied Materials and Interfaces, 11(38), 34560-34574.
Keywords General Materials Science
Publisher URL
Additional Information This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in l
ACS Applied Materials and Interfaces, copyright © American Chemical Society after peer review. To access the final edited and published work see