ABSTRACT
Dense biomaterial plays an important role in bone replacement. However, it fails to induce bone cell migration into graft material. In the present study, a novel bone graft substitute (BGS) consisting of porous gradient hydroxyapatite/zirconia composite (PGHC) and gelatin/chitosan slow-release hydrogel containing bone morphogenetic protein 2 and bone mesenchymal stem cells was designed and prepared to repair lumbar vertebral defects. The morphological characteristics of the BGS evaluated by a scanning electron microscope showed that it had a three-dimensional network structure with uniformly distributed chitosan microspheres on the surfaces of the graft material and the interior of the pores. Then, BGS (Group A), PGHC (Group B), or autologous bone (Group C) was implanted into lumbar vertebral body defects in a total of 24 healthy rhesus monkeys. After 8 and 16 weeks, anteroposterior and lateral radiographs of the lumbar spine, microcomputed tomography, histomorphometry, biomechanical testing, and biochemical testing for bone matrix markers, including Type I collagen, osteocalcin, osteopontin, basic fibroblast growth factor, alkaline phosphatase, and vascular endothelial growth factor, were performed to examine the reparative efficacy of the BGS and PGHC. The BGS displayed excellent ability to repair the lumbar vertebral defect in rhesus monkeys. Radiography, microcomputed tomography scanning, and histomorphological characterization showed that the newly formed bone volume in the interior of the pores in the BGS was significantly higher than in the PGHC. The results of biomechanical testing indicated that the vertebral body compression strength of the PGHC implant was lower than the other implants. Reverse-transcription polymerase chain reaction and western blot analyses showed that the expression of bone-related proteins in the BGS implant was significantly higher than in the PGHC implant. The BGS displayed reparative effects similar to autologous bone. Therefore, BGS use in vertebral bone defect repair appears promising.
Subject(s)
Bone Morphogenetic Protein 2/pharmacology , Bone Substitutes/pharmacology , Chitosan/chemistry , Durapatite/chemistry , Gelatin/chemistry , Lumbar Vertebrae/pathology , Mesenchymal Stem Cells/metabolism , Transforming Growth Factor beta/pharmacology , Zirconium/chemistry , Animals , Biomechanical Phenomena , Bone and Bones/diagnostic imaging , Bone and Bones/drug effects , Bone and Bones/metabolism , Delayed-Action Preparations/pharmacology , Gene Expression Regulation/drug effects , Hydrogels/chemistry , Macaca mulatta , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/ultrastructure , Osseointegration/drug effects , Osteogenesis/drug effects , Osteogenesis/genetics , Porosity , Recombinant Proteins/pharmacology , Wound Healing/drug effects , X-Ray MicrotomographyABSTRACT
OBJECTIVE: To evaluate the effects of porous gradient composites with hydroxyapatite/zirconia and autologous iliac in repair of lumbar vertebra body defects in dogs. METHODS: (1) New porous gradient hydroxyapatite/zirconia composites were prepared using foam immersion, gradient compound and high temperature sintering; (2) A total of 18 adult beagle dogs, aged five to eight months and weighted 10-13 kg, were randomly assigned into two subgroups, which were implanted with new porous gradient hydroxyapatite/zirconia composites (subgroup A in 12) or autologous iliac bone (subgroup B in 6); (3) The post-operative data were analyzed and compared between the subgroups to repair the vertebral body defect by roentgenoscopy, morphology and biomechanics. RESULTS: The porosity of new porous gradient hydroxyapatite/zirconia composites is at 25 poles per inch, and the size of pores is at between 150 and 300 µm. The post-operative roentgenoscopy displayed that new-bone formation is increased gradually, and the interface between composites and host-bone becomes became blur, and the new-bone around the composites were integrated into host-bone at 24 weeks postoperatively in subgroup A. As to subgroup B, the resorption and restructure were found at six weeks after the surgery, and the graft-bone and host-bone have been integrated completely without obvious boundary at 24 weeks postoperatively. Histomorphologic study showed that the amount of bone within pores of the porous gradient hydroxyapatite/zirconia composites increased continuously with a prolonged implantation time, and that partial composites were degradated and replaced by new-bone trabeculae. There was no significant difference between subgroups (P > 0.05) in the ultimate compressive strengths. CONCLUSION: New porous gradient hydroxyapatite/zirconia composites can promote the repair of bony defect, and induce bone tissue to ingrow into the pores, which may be applied widely to the treatment of bony defect in the future.
