Scaffold Design: A Review of Material and Immune Modulation in Bone Tissue Engineering

With the growing population and increased life expectancy, there has been a significant rise in orthopedic fractures and pathologies, leading to a heightened demand for effective orthopedic solutions. Bone tissue engineering (BTE) has emerged as a promising approach, employing scaffolds to regenerate bone tissue. This review highlights that successful material design for BTE requires a comprehensive understanding of the composition, structure, and biomechanics of natural bone. It also necessitates the careful selection of biomimetic natural or tunable synthetic materials, including polymers, bioceramics, metals, and composites. Furthermore, optimizing the physical, mechanical, and chemical properties of scaffolds is crucial, as these factors influence cell adhesion, proliferation, and differentiation. Special attention is given to the interaction between scaffolds and the host immune system, including the strategic incorporation of bioactive molecules and immunoregulatory cells. This holistic approach aims to engineer scaffolds that not only meet structural and functional demands but also foster an immune-compatible environment to enhance bone regeneration effectively. Careful selection of effective immunomodulation strategies for 3D scaffolds is crucial for creating a supportive immune microenvironment without negative effects. Various approaches can enhance the immune response, including incorporating smart nanomaterials into the surface of scaffolds, which contribute to immunomodulation, angiogenesis, and osteogenesis. Using stem cells for regenerating damaged bone tissue also improves the scaffold's immune response. Moreover, ionic and molecular doping are effective methods used to enhance immune response of scaffold in (BET), where specific ions like magnesium, zinc, and silicon are added to improve bioactivity and immune modulation capabilities. Finally, Wnt/β-catenin signaling pathway can be activated by integrating lithium into the scaffold surface, as lithium has anti-inflammatory properties and promotes bone formation by activating these pathways.