Anisotropic tissue biofabrication: conventional and advanced fabrication strategies for functional scaffolds

Natural tissues possess structurally organized architectures that enable specialized mechanical and functional behaviors. Anisotropy, defined as the directional dependence of material properties, is a key characteristic observed across a wide range of biological tissues, including bone, tendon, cartilage, and vascular systems. This review provides a comprehensive overview of anisotropy in native tissues by systematically analyzing its structural origins, including collagen fiber orientation, hierarchical organization, and gradient distributions. The degree and functional significance of anisotropy across different tissues are comparatively discussed to establish design benchmarks for scaffold fabrication. Conventional fabrication methods, including freeze-casting, mechanical anchoring, and electrospinning, are evaluated for their ability to induce anisotropy, although they remain constrained by restricted architectural control and scalability. Furthermore, advanced techniques such as additive manufacturing offer enhanced precision and tunability for engineering anisotropic scaffolds. Finally, emerging hybrid strategies that combine multiple fabrication principles provide promising solutions to overcome these limitations and achieve complex, tissue-mimetic architectures. Ultimately, this work presents a robust framework for designing next-generation anisotropic scaffolds that bridge the gap between natural tissues and engineered constructs.