Engineering a Whitlockite-Containing Macroporous Composite Cryogel with Silica Hybrid for Enhanced Vascularized Bone Regeneration

Recognizing the complexity of the bone regeneration cascade and understanding the adverse effects of using growth factors, it is crucial to develop a growth factor-free scaffold with multiple functions to modulate various aspects of the regenerative process. This study explores a novel macroporous multifunctional bone graft for bone regeneration, aiming to overcome complications associated with current treatment modalities. The study reveals enhanced bone regeneration and vascularization by integrating silica hybrid and nano-whitlockite (nWH) into cryogel-based composite scaffolds. The physicochemical properties, <i>in vitro</i> angiogenic and osteogenic potential, three-dimensional (3D) vasculogenesis, osteoclastogenesis, and proinflammatory responses of the composite cryogels were systematically examined. Results showed augmented effects for nWH-containing silica hybrid cryogels, particularly notable in the 1:0.5 WH2.5 group. Cryogels promoted angio- and vasculogenesis, and osteogenic differentiation while reducing osteoclast formation and proinflammatory responses <i>in vitro</i>. Optimal composition analysis consistently favored the 1:0.5 WH2.5 group. Implantation in a critical-sized cranial defect model in mice demonstrated enhanced vascularization and new bone formation. Thus, this study demonstrates the synergistic effect of silica hybrid and nWH in critical-sized bone defects.