The Basic And Clinical Research Of Coral Hydroxyapatite Combined With Growth Factor In Repairing Bone Defects

BackgroundBone defect and deformity caused by trauma,tumor and other bone diseases like inflammation have been common diseases in clinical.Bone regeneration remains a challenge in regenerative medicine,particularly in the cranio-maxillofacial region.Autologous bone grafts,which are transferred as either vascularized or non-vascularized tissue,have long been the first choice for reconstruction with osteoinductive and osteoconductive properties.Although this approach has yielded high rates of incorporation and initial revascularization,the disadvantages include donor site morbidity,limited availability,infection,hematoma formation,nerve injury and secondary fractures.This has triggered people's attention to the application of tissue engineering technology in the repair of bone defects.The bone tissue engineering prototype consists of a soluble osteogenic signal molecule and a variety of insoluble signaling molecules or matrix materials,and then develops a 3D scaffold with tissue induction and morphogenesis.Concentrated efforts have been made to develop materials that can mimic both function and structure of natural bone.Absorbable coralline hydroxylapatite(CHA)is a new type of bone substitute material based on coral and hydroxyapatite.Previous studies showed that coral is a biocompatible,osteoconductive,absorbable scaffold,and can serve as a delivery system for bone growth factors by adhesion to them.CHA reveals significant similarities to that of cancellous bone with interconnective three-dimensional porous structure,which provides a large internal surface for cells to adhere and migrate and allows the ingrowth of newly formed bone.Cell experiments and animal experiments have confirmed that CHA and cells co-culture does not produce immune rejection.Bone derived growth factors such as bone morphogenetic protein,vascular endothelial growth factor,transforming growth factor ? and insulin like growth factor,accelerate bone regeneration for their biological activity.It is known that the differentiation from bone marrow mesenchymal stem cell to osteoblast is the biological foundation of bone formation.In recent years,scholars have combined CHA with bone marrow mesenchymal stem cells or various growth factors to explore its osteogenic effect.Concentrated growth factors was first proposed by Sacco in 2006.CGF is produced by the centrifugation of the venous blood.The centrifugation speeds varies from 2400 to 2700 rpm to separate cells in the venous blood.This results in fibrin-rich blocks that are much larger,denser,and richer in growth factors than PRF-the second generation blood extract.This results in a better regenerative capacity and greater versatility when using the fibrin-rich block.CGF retains the advantages of PRF with a more simple preparation process and stronger osteoinductive property.Due to its higher tensile strength and viscosity,CGF can protect the growth factors better from proteolysis.Studies suggested that applying growth factors to bone defects results in greater osteogenic effects than applying nothing.At present,the research on the effect of CHA combined growth factor on bone induction is still in the primary stage,and there is a large research space.Research 1 Repair of rabbit cranial defects by concentrated growth factors in combination with coralline hydroxyapatite scaffoldsObjectivesThe aim of this study was to evaluate the effect of concentrated growth factor(CGF)in combination with absorbable coralline hydroxyapatite scaffolds on bone healing compared to CGF alone or coralline hydroxyapatite alone.Materials and MethodsForty rabbits were included in this randomized,prospective study.A circular defect with a diameter of 10mm was made on the parietal bone.The first group were filled with CHA/CGF and CHA;the second group filled CHA/CGF and CGF;the third group filled with CHA/CGF and autologous bone(Autologous skull was removed and then replanted in situ);the fourth group filled with CHA/CGF and void;the fifth group filled with CHA and CGF;the sixth group with CHA and autologous bone;the seventh group filled with CHA and void;the eighth group filled with CGF and autologous bone;the ninth group filled with CGF and void;the tenth group filled with autologous bone and void.The rabbits were sacrificed at sixth week and twelve week postoperatively and get the specimen.The bone formation was analyzed with microscopic computed tomography(micro-CT)and histological examination at the 6th week and 12th week.ResultsIn micro-CT analysis,bone volume and bone mineral density were greater in the CGF/CHA group than in CGF,CHA or void group at both 6th and 12th week(P<0.05),and there was no statistically significant difference between the CGF/CHA group and autograft group at 12th week(P>0.05).Histological examination showed new bone was distributed throughout the CHA scaffold in specimens from the CGF/CHA group,and new bone appeared only in the periphery region of the CHA scaffold from the CHA group at 6th week.The bone defects of CGF/CHA group were repaired fully with bone at 12th week,while those of the CHA group were repaired partly with bone and fibrous tissue was evident in the central region of the defects.ConclusionsCombination of CGF with CHA could enhance the bone healing considerably,which could be an attractive alternative for reconstruction of critical sized bone defect.Research 2 The clinical study of coral hydroxyapatite combined with growth factor in repairing bone defects around implantsObjectiveTo assess the added value of using CHA/CGF artificial bone in combination with immediate implants in reducing the bone dimensional changes occurring in the residual ridge and improving papilla index score.Material and methodsRandomized parallel controlled clinical trial to study the efficacy of grafting with CHA/CGF artificial bone in the gap between the implant surface and the inner bone walls when the implants were immediately placed in the anterior maxilla,and grafting with Bio-Oss as control.The changes between implant placement and 16 weeks later in the vertical crestal bone changes in relation to the implant were evaluated through CBCT.Papilla index score was recorded 16 weeks after implant placement.Mean changes were compared between the experimental and control sites using parametric statistics.ResultsA total of 20 implant sites in 20 subjects were included in the analysis(10 in the test group and 10 in the control group).The vertical crest dimension underwent marked changes during healing mainly at the buccal aspect of the alveolar crest where this reduction amount to 1.2mm in the test group and 1.1mm in the control group,and at the palatal aspect of the alveolar crest where this reduction amount to 0.6mm in the test group and 0.8mm in the control group,being these not statistically significant(P>0.05).The frequency distributions of the papilla index scores were not significantly different between the test group and the control group(P>0.05)ConclusionThe results from this clinical trial demonstrated that placing a CHA/CGF artificial bone reduced significantly the vertical crest bone resorptive changes after the immediate implantation in fresh extraction sockets.