Anisotropic collagen-based biomaterials for tissue repair: fabrication strategies and biomedical applications

Many native tissues exhibit well-defined structural anisotropy, and restoring this anisotropy is essential for functional tissue regeneration. As the predominant extracellular matrix protein, collagen exhibits distinctive mechanical properties and physiological functions owing to its specific orientation. For example, collagen fibrils form lamellar structures in the transparent cornea and align in parallel in ligaments and tendons. Accordingly, introducing anisotropic structures into collagen-based biomaterials to mimic native tissue architecture and provide an appropriate cellular microenvironment is crucial for advancing tissue-repair applications. However, conventional collagen-based biomaterials with homogeneous structures often fail to reproduce the complex architecture of natural tissues, limiting their applications in tissue repair. Herein, this review summarizes recent progress in the development, fabrication, and application of anisotropic collagen-based biomaterials for tissue repair. We first outline the hierarchical structure of collagen from the nanoscale to the macroscale. We then summarize collagen fibril arrangements in native tissues and highlight strategies and fabrication techniques used to generate anisotropic collagen-based biomaterials. Next, we discuss recent advances in applying these materials to tissue repair. Finally, we discuss the remaining challenges and future prospects of anisotropic collagen-based biomaterials for tissue repair.