Abstract
Current challenges in the biofabrication of stable, cell-seeded fibrin gels are faced with a lack of microstructural and mechanical properties, limiting their use as bone extracellular matrix-mimicking constructs. While current approaches focus on generating fibrin gels of various fibrinogen and thrombin concentrations, i.e. 5-50 mg mL(-1) and 1-250 units mL(-1), respectively, processes that modulate gel fibrillar alignment and mechanical properties have yet to be explored. Herein, it was demonstrated that the automated gel aspiration-ejection (GAE) of precursor fibrin hydrogels of low concentration (i.e. 1 mg mL(-1) fibrinogen and 0.5 units mL(-1) thrombin) resulted in their immediate compaction while tailoring their fibrillar alignment and mechanical properties for potential target applications. Furthermore, this gel microenvironment accelerated the osteoblastic differentiation of seeded mesenchymal stem cells and their matrix mineralization, in vitro. Therefore, the ability to modulate the properties of dense fibrin constructs through automated GAE may be a novel biofabrication approach for cell delivery in bone regeneration.