A review on gradient and hierarchical scaffolds: mechanical design and fabrication via electrospinning and extrusion techniques

Development of biomimetic scaffolds that mimic the complex structures and compositions of extracellular matrices is a promising approach in tissue engineering. This comprehensive review delves into the evolving and advancing field of gradient and hierarchical scaffolds in tissue engineering, with a particular emphasis on electrospinning-based and extrusion-based fabrication techniques, as well as their hybrid methodologies. We first introduce the fundamental concepts of biomimetic scaffold design in tissue engineering. Subsequently, we provide an overview of the design principles, mechanical considerations, and fabrication methods for creating gradient and hierarchical scaffolds that closely mimic the complex structures found in natural tissues. The applications of gradient and hierarchical scaffolds in various areas of tissue engineering, such as bone, cartilage, tendon, ligament, and vascular tissues, are also highlighted. Furthermore, the paper addresses current challenges in the field, including limitations in fabrication techniques, scalability issues, and the integration of smart and stimuli-responsive materials. It concludes by discussing emerging trends and future research directions, emphasizing the potential of these advanced scaffolds to revolutionize tissue engineering and regenerative medicine. This review aims to provide researchers and practitioners with clear insights into recent advancements, current challenges, and prospective directions in gradient and hierarchical scaffold design and fabrication.