Biomimetic collagen composite matrix-hydroxyapatite scaffold induce bone regeneration in critical size cranial defects

Although biomimetic scaffolds have been constructed to repair critical-size bone defects, the creation of composite scaffolds that can mimic the anisotropy of natural bone remains a major challenge. Herein, we have for the first time developed a biomimetic collagen composite matrix-hydroxyapatite (CCMH) scaffold, which highly resembles both the composition and the anisotropy hierarchical structure of natural bone. The CCMH scaffold was created through unidirectional freeze-casting and in situ peristaltic mineralization, resulting in uniformly distributed nano-hydroxyapatite on the porous collagen composite matrix (CCM) scaffold. The CCMH scaffold finely mimics the composition and anisotropic channel-like morphology of native bone, which exhibits high biocompatibility, excellent cellular activity and extraordinary osteogenic differentiation capability. Magnetic resonance imaging (MRI), micro-computed tomography (micro-CT) and histological analysis of rat models demonstrated that the CCMH scaffold significantly enhanced new bone formation and accelerated bone regeneration. The innovative unidirectional freezing-in situ peristaltic mineralization approach offers a robust technique for building biomimetic three-dimensional porous scaffolds with excellent biocompatibility and osteoinductivity, which show significant promise for use in bone repair and regeneration.