fig3
Figure 3. Overview of strategies for regenerative bone tissue engineering. The diagram highlights key approaches to achieve the essential properties for bone regeneration - osteoconductivity, osteoinductivity, and osteogenicity. Biomaterial design relates to the materials used such as bioceramics (e.g., hydroxyapatite), synthetic/natural polymers (e.g., PLA and collagen), composite materials, and metals for mechanical strength and structure to support regeneration. Cell-laden strategies leverage MSCs and ECs through their delivery via scaffolds, microgels, or hydrogels to generate pre-vascularized constructs supporting angiogenesis. Bioactive modifications utilize immunomodulation, cytokine signaling, and growth factors such as VEGF, BMPs, and TGF-β to support bone repair. Physical microenvironmental factors, including dimensionality (i.e., 2D vs. 3D), stiffness, elasticity, porosity, degradability, and mineralization, are critical for creating biologically relevant scaffolds. Mechanotransduction forces, such as cyclic loading and piezoelectric scaffolds, mimic physiological bone stresses. Automation and scalability, through tools such as bioprinting, microfluidics, and artificial intelligence, enable the efficient production of clinically relevant constructs. Created in BioRender. (Vignolo S, 2025; https://BioRender.com/3aa12q6). ECs: Endothelial cells; MSCs: mesenchymal stem cells; BMPs: bone morphogenetic proteins; VEGF: vascular endothelial growth factor.