Fabrication of compositionally and topographically complex robust tissue forms by 3D-electrochemical compaction of collagen.

Collagen solutions are phase-transformed to mechanically robust shell structures with curviplanar topographies using electrochemically-induced pH gradients. The process enables rapid layer-by-layer deposition of collagen-rich mixtures over the entire field simultaneously to obtain compositionally diverse multilayered structures. The in-plane tensile strength and modulus of the electrocompacted collagen sheet samples were 5200-fold and 2300-fold greater than those of the uncompacted collagen samples. Out-of-plane compression tests showed a 27-fold increase in compressive stress and a 46-fold increase in compressive modulus compared to uncompacted collagen sheets. Cells proliferated 4.9 times faster, and the cellular area spread was 2.7 times greater on compacted collagen sheets. Electrocompaction also resulted in a 2.9 times greater focal adhesion area than on regular collagen hydrogel. The reported improvements in the cell-matrix interactions with electrocompaction would serve to expedite the population of electrocompacted collagen scaffolds by cells. The capacity of the method to fabricate nonlinear curved topographies with compositional heterogeneous layers is demonstrated by sequential deposition of a collagen-hydroxyapatite layer over a collagen layer. The complex curved topography of the nasal structure is replicated by the electrochemical compaction method. The presented electrochemical compaction process is an enabling modality which holds significant promise for reconstruction of a wide spectrum of topographically complex systems such as joint surfaces, craniofacial defects, ears, nose, and urogenital forms.