Bioinspired Collagen-Apatite Nanocomposites for Bone Regeneration

• Collagen-apatite (Col-Ap) nanocomposite exhibits superior bone regeneration.
• Col-Ap nanocomposite scaffold stimulates bone-forming cells and vessel ingrowth.
• Col-Ap nanocomposite induces extracellular matrix secretion and mineralization.
• Osterix, vascular endothelial growth factor receptor 1, and transforming growth factor beta 1 are highly expressed in the Col-Ap nanocomposite.

IntroductionNatural bone has a complex hierarchical nanostructure composed of well-organized collagen fibrils embedded with apatite crystallites. Bone tissue engineering requires scaffolds with structural properties and functionality similar to the natural bone. Inspired by bone, a collagen-apatite (Col-Ap) nanocomposite was fabricated with bonelike subfibrillar nanostructures using a modified bottom-up biomimetic approach and has a potential role in the healing of large bone defects in unresolved apical periodontitis.MethodsThe bone regeneration potential of the Col-Ap nanocomposite was investigated by comparing it with inorganic beta-tricalcium phosphate and organic pure collagen using a critical-sized rodent mandibular defect model. Micro–computed tomographic imaging and histologic staining were used to evaluate new bone formation in vivo.ResultsWhen compared with the beta-tricalcium phosphate and collagen scaffolds, the Col-Ap nanocomposite scaffold exhibited superior regeneration properties characterized by profuse deposition of new bony structures and vascularization at the defect center. Immunohistochemistry showed that the transcription factor osterix and vascular endothelial growth factor receptor 1 were highly expressed in the Col-Ap group. The results indicate that the Col-Ap nanocomposite activates more bone-forming cells and stimulates more vascular tissue ingrowth. Furthermore, the Col-Ap nanocomposite induces extracellular matrix secretion and mineralization of rat bone marrow stem cells. The increased expression of transforming growth factor beta 1 may contribute to the formation of a mineralized extracellular matrix.ConclusionsThe present study lays the foundation for the development of Col-Ap nanocomposite–based bone grafts for future clinical applications in bone regeneration of large periapical lesions after apical curettage or apicoectomy.