Assessment of Migration of Human MSCs through Fibrin Hydrogels as a Tool for Formulation Optimisation.

Nasseem Salam,Sotiria Toumpaniari,Piergiorgio Gentile,Ana Marina Ferreira,Simon Partridge,Kenneth Dalgarno

doi:10.3390/ma11091781

Abstract

Control of cell migration is fundamental to the performance of materials for cell delivery, as for cells to provide any therapeutic effect, they must migrate out from the delivery material. Here the influence of fibrinogen concentration on the migration of encapsulated human mesenchymal stem cells (hMSCs) from a cell spheroid through fibrin hydrogels is tracked over time. Fibrin was chosen as a model material as it is routinely employed as a haemostatic agent and more recently has been applied as a localised delivery vehicle for potential therapeutic cell populations. The hydrogels consisted of 5 U/mL thrombin and between 5 and 50 mg/mL fibrinogen. Microstructural and viscoelastic properties of different compositions were evaluated using SEM and rheometry. Increasing the fibrinogen concentration resulted in a visibly denser matrix with smaller pores and higher stiffness. hMSCs dispersed within the fibrin gels maintained cell viability post-encapsulation, however, the migration of cells from an encapsulated spheroid revealed that denser fibrin matrices inhibit cell migration. This study provides the first quantitative study on the influence of fibrinogen concentration on 3D hMSC migration within fibrin gels, which can be used to guide material selection for scaffold design in tissue engineering and for the clinical application of fibrin sealants.

Highlights

Hydrogels, highly hydrated cross-linked polymers, are increasingly sought as tissue engineering scaffolds due to their hydrophilicity, permissive nutrient/waste exchange, and predisposition for biocompatibility [1,2].Fibrin, a protein biopolymer that simulates the final stage of the coagulation cascade, is routinely employed as a haemostatic agent [3]
Fibrin gels with final concentrations of 5 mg/mL to 50 mg/mL fibrinogen and 5 U/mL thrombin were used, based on concentrations used in the literature and to give a good range of properties
SEM micrographs were obtained of fibrin gels comprising 5, 20, and 50 mg/mL fibrinogen, and were analysed to assess fibre and pore sizes (Figure 2)

Summary

Introduction

Highly hydrated cross-linked polymers, are increasingly sought as tissue engineering scaffolds due to their hydrophilicity, permissive nutrient/waste exchange, and predisposition for biocompatibility [1,2].Fibrin, a protein biopolymer that simulates the final stage of the coagulation cascade, is routinely employed as a haemostatic agent [3]. Highly hydrated cross-linked polymers, are increasingly sought as tissue engineering scaffolds due to their hydrophilicity, permissive nutrient/waste exchange, and predisposition for biocompatibility [1,2]. Materials 2018, 11, 1781 for the cells to offer a therapeutic effect they need to migrate out of the gel and interact with native tissue. Adipose-derived human mesenchymal stem cells (hMSCs) have been delivered in fibrin to augment microfracture procedures in cartilage regeneration [11], with histological evaluation demonstrating superiority over the microfracture-only procedure. HMSCs are commonly identified as cells of particular interest for tissue engineering [12,13] Adipose-derived human mesenchymal stem cells (hMSCs) have been delivered in fibrin to augment microfracture procedures in cartilage regeneration [11], with histological evaluation demonstrating superiority over the microfracture-only procedure. hMSCs are commonly identified as cells of particular interest for tissue engineering [12,13]

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Discussion

Conclusion