Engineering Functional Collagen Scaffolds: Cyclical Loading Increases Material Strength and Fibril Aggregation

Abstract Variation in collagen fibril diameter in nature is a major factor determining biological material properties. However, the mechanism resulting in this fibril diameter difference is not clear and generally assumed to be cell‐dependent. It is certainly not possible so far to engineer this into implantable scaffold materials. This gap in our knowledge is crucial for the fabrication of truly biomimetic tissue‐like materials. We have tested the idea that fibril diameter can be regulated directly without cell involvement, using cyclical mechanical loading to promote fibril fusion. Specific loading regimes increased collagen fibril diameter (> 2 fold) in direct relation to cycle number, whilst thin fibrils disappeared. Tensile properties increased, producing a 4.5 fold rise in break strength. This represents the first demonstration of direct cyclical load‐promoted fibril fusion and provides a direct relation with material properties. The ability to control material properties in this way makes it possible to fabricate truly biomimetic collagen materials without cells.