Multiphasic Collagen Scaffolds for Engineered Tissue Interfaces

Abstract Hard–soft tissue interfaces pose unique challenges for regeneration due to architectural, mechanical, and compositional changes between tissues, which are difficult to incorporate into tissue engineering scaffolds. Multiphasic scaffolds are needed to better mimic structural and chemical changes through the incorporation of layers with distinct properties. A particular challenge in the production of multilayered constructs is achieving cohesion between layers. Herein, a novel system is developed, which combines sequential collagen self‐assembly and diffusion gradients in mineralization to produce multiphasic collagen scaffolds that have intrinsic connectivity and porosity between layers, with no need for adhesives or heat treatments. The scaffolds incorporate mineralized layers, wherein the mineralized collagen fibrils have intrafibrillar oriented mineral resembling bone, alongside unmineralized layers. The interface between mineralized and unmineralized layers is sharp and well defined, with nonmineralized fibrils inserting into the mineralized layer to create mechanical interlock and cohesion. Inspired by the complex architecture of the periodontal attachment apparatus (bone–ligament–cementum), it is demonstrated that the model system can be applied to the development of a trilayered collagen scaffold with potential for periodontal regeneration.