SIBTEN · Surface Curvature-mediated Immunomodulation for Bone Tissue Engineering in Non-load-bearing defects

Fractures in the craniofacial and alveolar regions are a significant health concern, with millions of cases reported each year. The standard treatment for these injuries is bone grafting, which is the second most common tissue transfer procedure worldwide, but it involves notable risks and limitations, such as donor site morbidity and limited availability. Bone tissue engineering (BTE) offers a promising alternative by using biomaterial scaffolds to stimulate regeneration. Traditionally, BTE has focused on recruiting progenitor cells and reducing immune responses; however, a recent paradigm shift recognizes the early immune system, particularly macrophages, as a crucial regulator of healing. Macrophages initially adopt a pro-inflammatory (M1) phenotype to start the healing process, then switch to an anti-inflammatory (M2) phenotype to support vascularization and bone formation. An improper switch can result in chronic inflammation and scaffold failure. A new strategy, immuno-driven bone regeneration, aims to leverage this regenerative capacity. While biochemical modifications are common, they can face stability issues and systemic side effects. The proposed research emphasizes a more reliable approach: applying physical modifications to a new class of injectable granular hydrogels. This innovative material will feature controlled 3D surface curvature, an underexplored yet highly promising method for influencing macrophage fate. The project will first test the hydrogels in vivo to evaluate their regenerative potential. The data collected will then be used to develop a physiologically relevant in vitro model, providing a detailed, mechanistic understanding of immune-driven bone healing. This innovative approach aims to provide a more reliable and less invasive treatment for bone defects, while also reducing the need for animal testing.