Polymer Microparticles with Defined Surface Chemistry and Topography Mediate the Formation of Stem Cell Aggregates and Cardiomyocyte Function

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 cell cultures, methods are required to introduce these onto microparticles without modification of their underlying morphology 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 routes. PLA microparticles with smooth or dimpled surfaces were functionalized with poly(poly(ethylene glycol) methacrylate) and poly[N-(3-aminopropyl)methacrylamide] brushes, chosen for their potential abilities to mediate cell adhesion. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry analysis indicated homogeneous coverage of the microparticles with polymer 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 cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs). The influence of surface chemistry 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 contractility. 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.