Abstract
Cell-laden hydrogel microspheres have shown encouraging outcomes in the fields of drug delivery, tissue engineering or regenerative medicine. Beyond the classical single coating with polycations, many other different coating designs have been reported with the aim of improving mechanical properties and in vivo performance of the microspheres. Among the most common strategies are the inclusion of additional polycation coatings and the covalent bonding of the semi-permeable membranes with biocompatible crosslinkers such as genipin. However, it remains challenging to characterize the effects of the interactions between the polycations and the hydrogel microspheres over time in vitro. Here we use a force spectroscopy-based simultaneous topographical and mechanical characterization to study polymer-to-polymer interactions in alginate microspheres with different coating designs, maintaining the hydrogels in liquid. In addition to classical topography parameters, we explored, for the first time, the evolution of peak/valley features along the z axis via thresholding analysis and the cross-correlation between topography and stiffness profiles with resolution down to tens of nanometers. Thus, we demonstrated the importance of genipin crosslinking to avoid membrane detachment in alginate microspheres with double polycation coatings. Overall, this methodology could improve hydrogel design rationale and expedite in vitro characterization, therefore facilitating clinical translation of hydrogel-based technologies.
Highlights
Cell-laden hydrogel microspheres have shown encouraging outcomes in the fields of drug delivery, tissue engineering or regenerative medicine
Simultaneous collection of topography and stiffness values was performed through nanoindentation measurements (Fig. 1a, right)
Our results indicate that the topography of genipin-crosslinked double poly-L-Lysine (GDP) microspheres is more similar to alginate-PLL formulation (AP) and AP crosslinked with genipin (APG) than it is to APP
Summary
Cell-laden hydrogel microspheres have shown encouraging outcomes in the fields of drug delivery, tissue engineering or regenerative medicine. Among the limitations of this microsphere type, the lack of long-term stability and poor mechanical properties lead to compromised biosafety in vivo[14,15] To address these issues, microsphere performance has been enhanced using additional polycation coatings and/or covalent bonding in the semi-permeable membranes[16]. To refine the biosystem design for clinical practice, there is an urgent need for techniques to help unravel the mechanisms leading to implant failure In this context, atomic force microscopy (AFM) is a powerful tool to characterize surface topography and can be a proxy to characterize intermolecular interactions. AFM can help fine-tune microsphere composition, determine the heterogeneity between batches and infer microsphere chances of biocompatibility[30,31]
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