Currently, the concept of engineered tissues depends on the ability of cultured cells to fabricate new tissue around a scaffold. This is inherently slow and expensive and has had limited success so far. We report here a new process for the cell‐independent, controlled engineering of biomimetic scaffolds by rapid removal of fluid from hyperhydrated collagen gel (or other) constructs, using plastic compression (PC). PC fabrication produces dense, cellular, mechanically strong native collagen structures with controllable nano‐ and microscale biomimetic structures. The huge‐scale shrinkage (> 100‐fold) provides the ability to introduce controllable mechanical properties, microlayering, and embossed interface topography without cell participation, but with high cell viability. Critically, this takes minutes rather than the conventional days and weeks. The rapidity and biomimetic potential of the PC fabrication process at the mesoscale opens a new route for the production of biomaterials and patient‐customized tissues. It also represents a new concept in ‘engineering’ tissues.

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.