Research On The Preparation And Performance Of 3D-printed Fully-biodegradable Porous Scaffolds For Bone Repair

With the advent of population aging and the national movement,bone defects become a common clinical disease,caused by not only the osteoporotic fractures,infections,tumors,osteomyelitis surgical debridement at middle and old age,but also various accidental injuries and congenital diseases at young and middle age,resulting in a serious issue on national physical and mental health.However,autologous injury healing is limited in size,and traditional treatments for autogenous and allogeneic bone transplantation are prone to cause fatal complications.Therefore,it is urgent to research and design three-dimensional bone repair scaffolds to meet the clinical requirements of specific bone defect,providing a bridging support for the bone defect and guides bone tissue healing.Polycaprolactone(PCL),as a clinically approved biomedical material,has the disadvantages of slow biodegradation,local acidic environment,and lack of biological activity.However,biomedical magnesium(Mg)has a fast degradation rate,the product is alkaline,and Mg ion has a bone-promoting effect.Based on the insufficient functionality of PCL,Mg/PCL composite materials were designed by introducing Mg powder into PCL matrix,which would exhibit many advantagements including controllable biodegradation,remarkable osteogenesis and the ability to stable physiological environment.In view of the complex and changing service physiological environment,Fused Deposition Modeling(FDM)technology based on digital design was employed to prepare a degradable bone repair scaffold with excellent comprehensive performance to achieve personalized and precise treatment of bone defect repair.Mg/PCL composite scaffolds were prepared by FDM technology using Mg powder and PCL particles as raw materials,and the physical and chemical properties were characterized.The service characteristics of the composite scaffold in simulated body fluid were studied.In addition,cell adhesion,migration,proliferation and differentiation were evaluated to reflect in-vitro biocompatibility of scaffolds.The new bone formation and mineralization were in vivo explored to reveal bone repair and healing during service process.The main conclusions are as follows:(1)n Mg-PCL(n=0,1wt.%,3wt.%,5wt.%,7wt.%,9wt.%)porous composite scaffolds were prepared by employing FDM technology.The scaffold structure was characterized,which the diameter is 13mm,height is 4.4mm,the pore diameter is 480±25?m,the fiber diameter is 300±25?m,the theoretical porosity is 73.56%,and the actual porosity is 66.03%.With the addition of Mg particles,the crystallinity of the composite scaffold decreased and was lower than that of the PCL scaffold.The melting point of scaffolds changed basically in accordance with the crystallinity trend.The compression curve of the scaffold is divided into two stages:elastic deformation(linear and nonlinear),plastic yield and collapse densification stage.The compressive strength is 3.6-6.6MPa and modulus is 35.4-68.9MPa,which are slightly lower than composite scaffolds reinforced by ceramic particles.(2)In-vitro degradation experiments show that PCL and n Mg-PCL scaffolds are corroded to form holes and cracks,and hydroxyapatite and a small amount of calcium salts are deposited on the surface,indicating that the scaffold has biological activity and bone integration capabilities.There is no evident change in the macrostructure and volume of scaffolds,the mechanical properties maintain good.Only the mechanical properties of composite scaffolds,with serious corrosion induced by high Mg content,are significantly reduced,but subsequently surface Ca-P deposition increases the modulus value of the scaffolds to a certain extent.When the scaffold is degraded,a small amount of Mg particles on the surface is preferentially corroded,leading to Mg²⁺release and the formation of holes and cracks.Water molecules penetrate into the scaffold fiber from the defects,Mg particles inside the fiber are further corroded,and PCL exhibits homogeneous hydrolysis.At the same time,Mg²⁺induces hydroxyapatite HA deposited on the surface.(3)Cell experiment results show that the cell proliferation effect of 3wt.%Mg-PCL scaffolds is more significant.The cells in the 1wt.%Mg-PCL and 3wt.%Mg-PCL scaffolds spread as flat shape,with a large number of cell antennas and greater cell adhesion density.ALP and AR staining of 3wt.%Mg-PCL scaffolds are deeper for characterizing osteogenic differentiation.Moreover,ALP activity,vascular endothelial growth factor(VEGF)and the expression levels of osteoblast differentiation-related collagen type-?(COL-?),osteopontin(OPN),and specific transcription factors(RUNX-2)are also higher.The results of in vivo scaffold implantation experiments indicates that the scaffolds provide a bridge for bone defects.Compared with the non-implanted scaffolds group,in which the scaffold and the bone defect are vaguely visible at 12 weeks,the new bones at both ends are connected to each other with a small amount of more mature bone is formed,and there is no hollow at the defect site after the 3wt.%Mg-PCL scaffold is implanted for 12 weeks.Based on the multi-scale analysis and evaluation of the surface morphology evolution,in-vitro biocompatibility,and in-vivo bone-promoting effects of the scaffolds,the Mg/PCL composite scaffold meets the physiological environment service requirements of bone defects.The Mg/PCL composite scaffold would be a promising biomaterial for achieving large bone regenerative repair,which deserves further research for clinical application transformation.