Rotation-based technique for the rapid densification of tubular collagen gel scaffolds

Type I collagen gel is often used as a tubular scaffold because of its easy molding properties as well as its biocompatibility, low immunogenicity and ability to be remodelled by cells. However, its highly hydrated structure contributes to its weak mechanical properties and reduces its ability to be handled, which is important in tubular tissue engineering. Although cell-driven remodelling of collagen matrices is known to reinforce their mechanical properties, this process can take weeks. This study introduces a novel, simple, and rapid technique using a rotational bioreactor to expel water and densify collagen under sterile conditions to generate denser and stronger collagen gel scaffolds. This process produces a dense tubular-shaped collagen gel which, compared to standard collagen gel scaffolds, shows a decreased wall thickness and a four-fold increase in collagen concentration. A denser collagen fiber network observed by immunofluorescence staining and mechanical characterisation shows a twenty-fold increase in the elastic modulus of the dense constructs which maintain cell viability inside the scaffold. Moreover, by simply modifying the scaffold mold, customised shapes and sizes can be obtained to provide a wide range of applications, including complex tubular geometries and multi-layered scaffolds for the culture of various cell types and tissues.