Abstract
Recent work demonstrated that 3D fibrin scaffolds function as an effective substrate for engineering tissues from pluripotent stem cells. However, the rapid degradation rate of fibrin remains a major limitation when differentiating human pluripotent stem cells for tissue engineering applications. The addition of crosslinking agents, such as genipin, during the polymerization process increases scaffold stability while decreasing the degradation rate of fibrin. Genipin crosslinking alters the physical characteristics of the fibrin scaffolds, which influences the behaviour of the differentiating cells seeded inside. It also possesses neuritogenic and neuroprotective properties, making it particularly attractive for engineering neural tissue from pluripotent stem cells. Here we show that genipin enhances neuronal differentiation of neural progenitors derived from human induced pluripotent stem cells (hiPSCs) in 2D culture and genipin concentration influences the morphological and mechanical properties of 3D fibrin scaffolds. These mechanically stable genipin-crosslinked fibrin scaffolds support hiPSC-derived neural aggregates and induce neurite outgrowth while remaining intact for 2 weeks as opposed to 5 days for unmodified fibrin scaffolds.
Highlights
Human pluripotent stem cells can divide indefinitely and adopt the identity of any cell type in the body, giving them the potential to regenerate specific tissue types[1, 2]
SC-derived neural progenitors seeded on 2D laminin surfaces were treated with a range of genipin concentrations to determine its effect on their behavior
Genipin at low concentrations was non-toxic and enhanced neurite outgrowth in neural aggregates derived from human induced pluripotent stem cells (hiPSCs)
Summary
Human pluripotent stem cells can divide indefinitely and adopt the identity of any cell type in the body, giving them the potential to regenerate specific tissue types[1, 2] These two properties make them an attractive option for treating degenerative diseases and traumatic injuries that occur in the central nervous system[3]. A blood derived protein, plays a critical role in coagulation During this process, the enzyme thrombin cleaves fibrinogen into fibrin monomers that assemble into a fibrous 3-dimentional network with physical properties resembling soft tissue[12,13,14]. We demonstrated that these 3D fibrin-genipin scaffolds promoted the survival and neurite outgrowth of human iPSC derived neural progenitors while remaining intact over a two-week culture period
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