Injectable biomaterials have evolved from serving as simple structural fillers to acting as multi-functional systems capable of directing human mesenchymal stromal cell (hMSCs) response. However, the selection of appropriate design parameters for injectable polymeric microbeads for translational applications remains a challenge. We have demonstrated promising strategies to address this need by tailoring the architectural features of injectable microbeads to act as modulating moieties of attachment and osteogenic response in hMSCs [1, 2].
Topography offers a vital tool to be harnessed for guiding cell fate, since topographical features tend to be more robust than surface chemistry and can be modified in terms of size, shape and degradation rate. We have demonstrated that topographical patterning of polylactic acid microbeads offers cell-instructive 3D microenvironments to allow the modulation of hMSCs fate by eliciting the desired downstream response without adding exogenous bioactive supplements. Topographically-patterned microbeads of varying microscale features (acting as braille for cells) were produced by phase separation of a sacrificial component from polylactic acid during fabrication. We established that culturing hMSCs on dimpled microbeads recreates mechanical aspects of the endosteal niche and exhibited varying morphological, integrin-mediated adhesion and proliferation responses. Additionally, significantly increased expression of osteogenic markers in hMSCs cultured on dimpled microbeads relative to conventional smooth microbeads was observed in the absence of exogenous biochemical factors. The cells also exhibited significantly altered metabolic profiles on different microbeads designs and resulted in varying histological characteristics in vivo . Surface-functionalised textured microbeads were used to investigate the relative importance of surface chemistry over topography on the formation of 3D hMSCs-microbeads aggregates for 3D culture applications .
Our work delivers new guiding principles for the design of 3D cell-material interfaces, and opens up new avenues for engineering tailored injectable materials for applications spanning regenerative therapies, disease models, cell culture and advanced cell delivery systems.
 Amer, M., Alvarez-Paino, M., McLaren, J., Pappalardo, F., Trujillo, S., Wong J., Shrestha, S., Abdelrazig, S., Lee, JB., Stevens, L., Kim, D, Gonzalez-Garcia, C., Needham, D., Salmeron-Sanchez, M., Shakesheff, K., Alexander, M., Alexander, C., Rose, F. (2021) “Designing Topographically Textured Microparticles For Induction and Modulation of Osteogenesis in Mesenchymal Stem Cell Engineering”. Biomaterials, 266, 120450
 Alvarez-Paino, M., Amer, M., Nasir, A., Cuzzucoli Crucitti, V., Thorpe, J., Burroughs, L., Needham, D., Denning, C., Alexander, M., Rose, F., Alexander, C. (2019) “Polymer Microparticles With Defined Surface Chemistry And Topography Mediate The Formation Of Stem Cell Aggregates And Cardiomyocyte Function"". ACS Applied Materials & Interfaces, 11(38) 34560."