Mineralized Collagen-Based Composite Bone Materials for Cranial Bone Regeneration in Developing Sheep

Cranial bone defects remain a great challenging problem in clinical settings, the influences of which are serious because of the intricate complications and related social problems, especially for young children with rapidly growing skulls. Currently, an increasing number of bone materials are being developed for cranial bone defects repair. In this study, two different biodegradable composite bone materials based on mineralized collagen (MC), with compact/porous structure, were constructed to promote bone regeneration for large cranial bone defect repair of one-month-old baby sheep. The porous MC (pMC) scaffold had interconnected porous structure with a porosity of about 73% and a 20-150 μm pore size range, and the compact MC (cMC) showed no distinct pore structure. Mechanical tests indicated that the compressive strength and elastic modulus of cMC and pMC were comparable with those of natural compact and cancellous bone, respectively. Both of these two MC scaffolds possessed good biocompatibility and supported osteoblasts adhesion and proliferation in vitro. A one-month-old sheep cranial bone defect model was first established to investigate the cranial bone regeneration behaviors in vivo, which was evaluated by CT imaging, X-rays scans, and histological assessments. It was found that the pMC promoted bone ingrowth from the diploic layer of surrounding cranium and dura mater-derived osteogenesis at three months after surgery, along with gradual biodegradation. In contrast, the cMC had very little biodegradation but could promote bone formation beneath the scaffold through dura mater-derived osteogenesis pathway. Furthermore, Ti-mesh restricted the growth of surrounding cranial bone in the rapidly growing sheep, thereby causing obvious deformation of the skull at six months after surgery, whereas no visible geometric deformation of skull occurred in the cMC and pMC groups. Our findings suggested that the MC-based composite bone materials have great promise for the repair of large cranial bone defects in a developing skull.