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

Abstract

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.

Droplet Microfluidic Optimisation Using Micropipette Characterisation of Bio-Instructive Polymeric Surfactants

“…Microparticles loaded with drugs, growth factors or proteins, are able to achieve specific and controlled delivery to cell cultures or as treatments, with the release being tuned further by adjusting the size and internal structure of the particles [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Alternatively, they can be used as a tool to direct stem cell fate, modulate the phenotype of other cells or to provide a realistic 3D environment for culture by forming scaffolds [ 3 , 12 , 13 , 14 ]. Their abilities in this role can be further enhanced by introducing specific chemistries, topographies or porosity [ 12 , 13 , 15 ].…”

“…Alternatively, they can be used as a tool to direct stem cell fate, modulate the phenotype of other cells or to provide a realistic 3D environment for culture by forming scaffolds [ 3 , 12 , 13 , 14 ]. Their abilities in this role can be further enhanced by introducing specific chemistries, topographies or porosity [ 12 , 13 , 15 ].…”

“…Poly(vinyl alcohol) (PVA) is frequently used to stabilise PLA/PLGA particles, due to the benefits of its polymeric structure [ 5 , 12 , 13 , 14 , 15 , 18 , 38 ]. However, in instances where the particle surface chemistry is important for the application, PVA will dominate this particle characteristic and so screen its effects.…”

Achieving Microparticles with Cell‐Instructive Surface Chemistry by Using Tunable Co‐Polymer Surfactants

“…This is particularly important as topography influences eukaryotic cell and bacterial surface attachment. [ 11–13 ] As a consequence, it is important to move from the design of 2D to 3D structures in order to gain a deeper understanding of the interaction of cells with their immediate extracellular environment and, consequently, derive more realistic biological models/assays that mimic real‐life conditions. [ 14 ] Polymeric microparticles are a simple 3D structure that have numerous healthcare applications including tissue engineering, diagnostics, and drug delivery.…”

“…[ 16,17 ] This presents a problem for biomaterials, as numerous studies have shown that biological‐surface interactions are dependent on surface chemistry. [ 13,16,18,19 ] For example, the presence of residual surfactant, such as the commonly used poly(vinyl alcohol‐co‐vinyl acetate) (PVA), has been shown to mask surface chemistry and impact on the resultant bacterial attachment properties [ 16 ] Thus, new approaches are required to produce particles which exhibit diverse surface chemistries where the process of preparation does not interfere with surface chemistry.…”