A primer on fabricating bioactive regenerative scaffolds – from materials and surface properties to microenvironment

Scaffold-based regenerative medicine is based on the creation of biomaterial constructs that effectively mimic the native tissue extracellular matrix (ECM), guiding cell behavior and enhancing functional tissue regeneration. Achieving this requires a multifaceted approach including careful material selection, control over scaffold architecture, enhancement of bioactivity, and the application of appropriate fabrication techniques. This review offers a comprehensive exploration of these core design principles, equipping researchers with the knowledge to engineer successful scaffolds for a range of regenerative applications. The review examines a spectrum of biocompatible materials and their surface characteristics like roughness, topography and wettability carefully weighing their strengths and limitations with respect to mechanical properties, degradation kinetics, potential immunogenicity and bioactivity. Furthermore, scaffold architecture—encompassing pore size, interconnectivity, and fiber alignment—plays a crucial role in mediating cell infiltration, nutrient transport, and tissue organization will be discussed. The review also covers the different aspects of increasing scaffold bioactivity like functionalization with cell adhesion motifs, incorporation of encapsulated growth factors, phytoconstituents and immunomodulation to create a pro-regenerative microenvironment. Finally, the review discusses the application of various techniques like 3D printing and electrospinning among others in scaffold fabrication. By effectively integrating these elements, researchers can design scaffolds that not only provide structural support but also actively orchestrate the regenerative process for better treatment outcomes.