| ObjectivesPresent study focuses on the fabrication of a bioactive customized bone graft scaffold by combination of rapid prototyping technology and biomimetically-functionalized strategy,then the scaffold was seeded with BMSCs to development of customized tissue engineering bone for precisely and personalized reconstruction of bone defects in maxillofacial region.Materials and methodsTo fabricate a biomimetically functionalized apatite-collagen-polycaprolactone(Ap-Col-PCL)composite scaffold.Firstly,a porous PCL constructs was fabricated by rapid prototyping(RP)fabrication technology,then it was functionalized by freeze-dried collagen incorporation and simulated body fluid(SBF)biomimetic deposition.The Ap-Col-PCL composite scaffold was characterized by field emission scanning electron microscopy(FESEM),micro-CT and thermogravimetric analysis(TGA).The hydropilicity and mechanical property of the Ap-Col-PCL scaffold was measured by water contact angle(WCA)measurement and compression tests.Cell Counting KIT-8(CCK-8)and con-focal laser scanning microscope were further used to evaluate the biocompatibility of the Ap-Col-PCL construct.The osteoconductivity of the Ap-Col-PCL scaffold was further evaluated by in vivo critical-sized segmental long bone defect implantation in rabbit radius.Furthermore,a beagle dog's maxillary bone defect was developed by presurgical simulation based on the skull CT images.Then,the beagle dog's customized bone cutting guide plates and PCL scaffolds were fabricated by rapid manufacturing.After biomimetical functionalization and bone marrow derived stem cells(BMSCs)seeding,the customized Ap-Col-PCL scaffold was implanted to the bone defect,which was rescted with the guidance of the cutting guide.Aftrer a period of 12 weeks' observation,the animals were sacrificed to obtain the defect sites,the newly formed bone tissue and the osteoconductivity and osteointegration capacity of Ap-Col-PCL construct were evaluated by Micro-CT and histomorphormetric analysis.ResultsControllable three-dimensional(3D)macro-porous PCL framework was fabricated by rapid prototyping technology.Ap-Col-PCL composite scaffold was characterized with hierarchical architectures of a nanoscale platelike apatite coating on the microporous collagen networks,which homogeneously filled in the macroporous PCL frameworks mimics the bone mineral in composition and structure,with a favorable biocompatible property and compressive modulus(68.75 ± 3.39 MPa)similar to that of cancellous bone.Moreover,in vitro cell culture assay and in vivo critical-sized bone defect implantation demonstrated that Ap-Col-PCL construct could not only significantly increase the cell adhesion capability(2.0-fold),promote faster cell proliferation but also successfully bridge the segmental long bone defect within 12 weeks with much more bone regeneration(5.2-fold),better osteointegration(7.2-fold),and a faster new bone deposition rate(2.9-fold)compare to PCL group.The custom-made positioning guides permite simple and precisely surgical bone resection during the surgery,the customized bone graft substitutes could match the bone defect in the beagels maxillary completely,after a period 12 weeks,the customized bone graft substitutes obtain maximized maxillary bone regeneration and reconstruction.Conclusions1.Our study demonstrated that biomimetically ornamented Ap-Col-PCL scaffold exhibit a favorable mechanical property,more bone tissue ingrowth,and better osteointegration capability as an effective bone graft substitute for critical-sized bone defect treatment in rabbit radius.2.Meanwhile,it can also harness the advantages of RP technology and biomimetically functionalization strategy to fabricate customization of the shape and size of Ap-Col-PCL implants for complex bone treatment.3. Better bone repair and regeneration was observed after 12 weeks implantion of beagels dog's BMSCs seeded customized scaffolds. Meanwhile, a long-term observation or osteogenic bioactive facor are needed for maximum maxillary bone defect treatment. |
PDF Full Text Request