The Fabrication Of Scaffold Reinforced By Resorbable Fibers For Bone Tissue Ingineering And Their Medical Applications

Currently,orthopedic reconstruction procedures stemming from trauma,tumor,deformity,degeneration and an aging population have dramatically increased,triggering a high demand on the advancement of bone implant technology.An ideal scaffold for bone repair there is some characteristics that it must have.It must be highly porous and channel connectivity to allow cell penetration.At the same time,it should provide enough mechanical support especially at early stage.But,traditional porous scaffolds have unsatisfactory mechanical properties for load-bearing sites.Besides,too high porosity will lead to low mechanical properties of the scaffolds.So,and how to balance the relationship between high porosity and high strength of the bone scaffold have become a key study.The scaffold reinforced by resorbable fibers in our study may resolve the problems obove.Polyglicolid(PGA)has many particular properties,such as good biocompatibility and safety in vivo,that make it extensively used in medical applications,but the rate of degradation in the body is too fast,the new organization can not afford to the body load when PGA had lost their mechanical properties.poly(D,L-lactide-co-glycolide)(PLGA)also has good compatibility to human tissue.However,the pure PLGA scaffold has low mechanical properties and the pores formed slowly.Therefore,this study aimed to combine the characteristics of both the PLA and PLGA to fabricate the scaffold reinforced by resorbable PGA fibers and pore formation in situ as PGA fiber degradation.The PGA fiber degradated fast and informed high-connectivity pores in situ,but the PLGA body degradated slowly and continued to maintain the mechanical support,in order to match the ingrowth of bone tissue.Experimental parts:1.The traditional porous scaffold HA/PLGA fabricated by particle leaching was combined with dopamine,ossotide and BMP-2 to investigate cell proliferation,ALP,calcium quantification,mineralization in SBF and repair effect of tibial defects in vivo.The results showed that this traditional porous scaffold with dopamine coating can be more efficient on combining bioactive factors.It can improve mineralization ability of HA/PLGA.The tibial defect repairmental experiment indicated more obvious mineralization with dopamine coating or BMP-2 combine after dopamine coating,but none of them can achieved ideal bone repairment effect.Due to the poor mechanical properties and poor connectivity of the pores,this traditional porous scaffold failed to repair weight-bearing bone defect,which has yet improve PLGA material-based scaffold below.2.Cotton-like PGA fibers were fabricated by melt centrifugal spinning.We observed its widely –distribution diameters ranging from 60 nm to 167 um by Scanning Electron Microscopy.Then we evaluated the mechanical properties of PGA fibers fabricated at different temperatures.Mechanical tests showed that the PGA fibers prepared at 260°C had the best tensile strength and were selected for subsequent experiments.3.In the third part,PGA fiber-reinforced PLGA composite scaffolds were prepared,and its mechanical properties with different fiber content scaffolds were evaluated.The addition of fiber significantly improved the compressive strength and flexural strength of scaffold,and the compressive strength reached to 38 MPa,which was more than 30 times higher than that without fiber-reinforced group.When the content is 40%,the fibers can be tightly bound in the matrix and have the best mechanical properties.This content group was selected for subsequent experiments.4.We carried out the degradation in vitro of this scaffold.The set specimens were immersed in PBS at 37? for 0,2,4,and 8 weeks,and were then tested in PH value change,weight loss and compressive strength.As the PGA fibers degradation,connective pores were achieved.The high strength were maintained for 2 weeks of immersion,depending on fiber degradation rate and the PLGA body.By SEM,we found that,it formed parallel rift when the PGA fiber began to degrade and then fractured leading to the loss of continuity.Connective pores or channels were observed in composite after fibers dissolution.5.Muscle embedding experiments in rabbits were conducted to further investigate the degradation behavior of PGA fiber-reinforced scaffold.The group without fiber-reinforcement showed significant degradation of the matrix and mechanical strength decrease;the PGA fiber-reinforced group maintained good mechanical properties within 4 weeks,then gradually degraded into broken rods.The fibers lost continuity,and disappeared which formed pores in 8 weeks.6.By rabbit radius defect repair experiment,we found,the PLGA scaffold reinforced by PGA fibers showed better repairmen effect.While the repairmen effect of group without fiber-reinforcement was not satisfactory.PGA fiber/PLGA scaffold could provide better mechanical support at early stage,while later,the pores formed gradually along with the degradation of PGA fibers to guiding new bone formation.This high-strength,pore formation in situ scaffold reinforced by degradable fibers can solve the contradiction between high-strength and high-porosity,and is confirmed in animal experiments.It is worth further investigation in order to make better use of it in bone tissue engineering.7.In vivo osteogenesis of PGA fiber reinforced HA/PLGA composite scaffolds combined with DOPA-IGF1.The bone induction of the scaffolds equipped with DOPA-IGF1 was significantly higher than that of the pure material groups.The content of DOPA-IGF1 loaded on the material was affected by the porosity of the scaffolds.Overall,scaffold materials with the growth factor and 40% PGA fiber content had the best effect on bone repair in vivo.The results confirmed that the biodegradation rate of the composites matched with the speed of bone reconstruction,and further verified the biocompatibility,osteogenesis and growth factor carrying capacity of the composite scaffolds.The important role of DOPA-IGF1 in promoting osteogenesis repair in vivo was also exhibited.In summary,the PGA fiber-reinforced scaffold can achieve dual effects of mechanical enhancement and form connective pores in-situ,which is expected to solve the conflict between high strength and porosity of scaffold.And at the same time,it can effectively carry growth factors for better repairmen of bone defect.