An Interlocked Bone/Fiber Construct Recapitulating the Native Soft‒Hard Tissue Interfaces for Periodontal Complex Regeneration in Pigs

Abstract The repair of periodontal complexes poses a significant challenge due to the lack of functional material constructs that can recapitulate the hierarchically interlocked structures of the soft–hard tissue interfaces within periodontium. Here, a bioinspired construct is fabricated by engineering interlocked bone–fiber interfaces within its hierarchical architectures to mimic the multiscale features found in native periodontal ligament (PDL)‒bone enthesis. The 3D‐printed bone module and electrospun fiber module of the bioinspired constructs offered suitable architecture, biomechanics, and cytokine landscapes to recruit reparative cells and promote their osteogenic and fibrogenic differentiation. At the interfaces of the dual‐module construct, the electrospun nanofibers of the fiber module are inserted into the bone module owing to various intermolecular interactions, which facilitate strong conjunction between the dual modules and provided biophysical gradients along the inserted nanofibers, similar to the microstructure and micromechanics of PDL‒bone insertions. When the constructs are placed in periodontal defects in pigs for 12 weeks, the alveolar bone is restored to its native level, and newly formed mature collagen fibers are inserted into the regenerated alveolar bone, culminating in superb integration between the soft and hard tissue interfaces. The findings demonstrate that bioinspired constructs with interlocked bone–fiber interfaces can regenerate complex soft‒hard tissue interfaces in pigs.